Physician/Patient Choice of Either High-Dose Recombinant Interferon Alfa-2B or Ipilimumab, Versus Pembrolizumab in Treating Patients With Stage III-IV High Risk Melanoma That Has Been Removed by Surgery

May 1, 2026 updated by: National Cancer Institute (NCI)

A Phase III Randomized Trial Comparing Physician/Patient Choice of Either High Dose Interferon or Ipilimumab to MK-3475 (Pembrolizumab) in Patients With High Risk Resected Melanoma

This randomized phase III trial studies how well pembrolizumab works compared with the current standard of care, physician/patient choice of either high-dose recombinant interferon alfa-2B or ipilimumab, in treating patients with stage III-IV melanoma that has been removed by surgery but is likely to come back or spread. High-dose recombinant interferon alfa-2B may help shrink or slow the growth of melanoma. Immunotherapy with monoclonal antibodies, such as ipilimumab and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether pembrolizumab is more effective than the current standard of care in treating patients with melanoma.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To compare overall survival (OS) of patients with resected stage III and IV melanoma treated with physician/patient choice of either high dose interferon recombinant interferon alfa-2b (alfa-2b) or ipilimumab versus MK-3475 (pembrolizumab).

II. Among patients who are PD-L1 positive, to compare OS of patients with resected stage III and IV melanoma treated with physician/patient choice of either high dose interferon alfa-2b or ipilimumab versus MK-3475 (pembrolizumab).

III. To compare relapse-free survival (RFS) of patients with resected stage III and IV melanoma treated with physician/patient choice of either high dose interferon alfa-2b or ipilimumab to MK-3475 (pembrolizumab).

SECONDARY OBJECTIVES:

I. To estimate OS and RFS for patients who are PD-L1 negative or PD-L1 indeterminate in this population.

II. To compare OS and RFS of patients between the two arms within PD-L1 positive and negative subgroups and to look at the interaction between PD-L1 (positive versus negative) and treatment arm.

III. To assess the safety and tolerability of the regimens.

ADDITIONAL OBJECTIVES:

I. To bank tissue and whole blood in anticipation of future correlative studies in this patient population.

II. To evaluate PD-L1 expression through immunohistochemistry assay. III. To evaluate the effect of treatment-related side effects that may have an impact on the health-related domains of quality of life (QOL) using the Functional Assessment of Cancer Therapy (FACT)-Biological Response Modifiers (BRM), European Quality of Life Five Dimension Three Level Scale (EQ-5D-3L), and Functional Assessment of Chronic Illness Therapy Diarrhea (FACIT-D) between patients treated with physician/patient choice of either high-dose interferon alfa-2b or ipilimumab and MK-3475 (pembrolizumab).

IV. Pharmacokinetic (PK) and anti-drug antibody (ADA) testing will be performed on all patients receiving MK-3475 (pembrolizumab).

TRANSLATIONAL OBJECTIVES RELATED TO T-CELL RECEPTOR BETA CHAIN SEQUENCING:

I. To evaluate the association between TCR beta variable gene (TRBV) haplotype and grade 3-4 immune-related adverse events (irAEs) among stage III melanoma patients treated with adjuvant ipilimumab or pembrolizumab.

II. To describe the TRBV haplotype distribution among this cohort of patients studied.

TRANSLATIONAL MEDICINAL OBJECTIVE RELATED TO ASSOCIATION OF CIRCULATING TUMOR DNA (ctDNA) WITH RELAPSE-FREE SURVIVAL IN HIGH-RISK, RESECTED MELANOMA PATIENTS.

I. To evaluate associations between pretreatment ctDNA (present versus absent) and relapse within 2 years of randomization in a case-control analysis across treatment arms.

II. To evaluate associations between pretreatment ctDNA (present versus absent) and relapse within 2 years of randomization in a case-control analysis across treatment arms.

III. To evaluate associations between pretreatment ctDNA and relapse within 2 years of randomization in a case-control analysis within each treatment arm (after treatment arm data are unblinded to investigators).

IV. To evaluate associations between "early-on treatment" ctDNA levels and relapse within 2 years of randomization.

V. To describe ctDNA levels at end of therapy and time of relapse.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I:

INDUCTION THERAPY: Patients receive high-dose recombinant interferon alfa-2B intravenously (IV) over 20 minutes on days 1-5. Treatment repeats weekly for 4 weeks in the absence of disease progression or unacceptable toxicity. Or patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 3 weeks for a total of 4 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive high-dose recombinant interferon alfa-2B subcutaneously (SC) on days 1, 3, and 5. Treatment repeats every 6 weeks for up to 48 weeks in the absence of disease progression or unacceptable toxicity. Or patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for 3 years in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity.

Patients undergo computed tomography (CT) scan, positron emission tomography (PET) scan, magnetic resonance imaging (MRI) and blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 30 days, 6 and 12 weeks, every 3 months for 2 years, every 6 months for 3 years, and then every 12 months for 5 years.

Study Type

Interventional

Enrollment (Actual)

1301

Phase

Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Canada
- British Columbia
  - Vancouver, British Columbia, Canada, V5Z 4E6
    - BCCA-Vancouver Cancer Centre
- New Brunswick
  - Moncton, New Brunswick, Canada, E1C 8X3
    - The Vitalite Health Network - Dr Leon Richard Oncology Centre
- Ontario
  - Barrie, Ontario, Canada, L4M 6M2
    - Royal Victoria Regional Health Centre
  - Hamilton, Ontario, Canada, L8V 5C2
    - Juravinski Cancer Centre at Hamilton Health Sciences
  - Kingston, Ontario, Canada, K7L 2V7
    - Kingston Health Sciences Centre
  - Kitchener, Ontario, Canada, N2G 1G3
    - Waterloo Regional Health Network
  - London, Ontario, Canada, N6A 4L6
    - London Regional Cancer Program
  - Mississauga, Ontario, Canada, L5M 2N1
    - Trillium Health Partners - Credit Valley Hospital
  - Oshawa, Ontario, Canada, L1G 2B9
    - Lakeridge Health Oshawa
  - Ottawa, Ontario, Canada, K1H 8L6
    - Ottawa Hospital and Cancer Center-General Campus
  - Sault Ste. Marie, Ontario, Canada, P6B 0A8
    - Algoma District Cancer Program Sault Area Hospital
  - Thunder Bay, Ontario, Canada, P7B 6V4
    - Thunder Bay Regional Health Science Centre
  - Toronto, Ontario, Canada, M5G 2M9
    - University Health Network-Princess Margaret Hospital
  - Toronto, Ontario, Canada, M4N 3M5
    - Odette Cancer Centre- Sunnybrook Health Sciences Centre
  - Windsor, Ontario, Canada, N8W 2X3
    - Windsor Regional Cancer Centre
- Quebec
  - Laval, Quebec, Canada, H7M 3L9
    - Hopital de la Cite-de-la-Sante
  - Montreal, Quebec, Canada, H3H 2R9
    - The Research Institute of the McGill University Health Centre (MUHC)
  - Québec, Quebec, Canada, G1R 2J6
    - CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
  - Sherbrooke, Quebec, Canada, J1H 5N4
    - Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
- Saskatchewan
  - Regina, Saskatchewan, Canada, S4T 7T1
    - Allan Blair Cancer Centre
  - Saskatoon, Saskatchewan, Canada, S7N 4H4
    - Saskatoon Cancer Centre
Ireland
- Co Dublin
  - Dublin, Co Dublin, Ireland, 4
    - Saint Vincent's University Hospital
- Co Galway
  - Galway, Co Galway, Ireland
    - University College Hospital Galway
- Co Waterford
  - Waterford, Co Waterford, Ireland, 9
    - University Hospital Waterford
United States
- Alabama
  - Birmingham, Alabama, United States, 35233
    - University of Alabama at Birmingham Cancer Center
- Arizona
  - Phoenix, Arizona, United States, 85004
    - Cancer Center at Saint Joseph's
  - Scottsdale, Arizona, United States, 85258
    - Virginia G Piper Cancer Care-Del Camino
  - Tucson, Arizona, United States, 85719
    - Banner University Medical Center - Tucson
  - Tucson, Arizona, United States, 85719
    - University of Arizona Cancer Center-North Campus
- Arkansas
  - Little Rock, Arkansas, United States, 72205
    - University of Arkansas for Medical Sciences
  - Rogers, Arkansas, United States, 72758
    - Highlands Oncology Group - Rogers
- California
  - Anaheim, California, United States, 92806
    - Kaiser Permanente-Anaheim
  - Auburn, California, United States, 95602
    - Sutter Auburn Faith Hospital
  - Baldwin Park, California, United States, 91706
    - Kaiser Permanente-Baldwin Park
  - Bellflower, California, United States, 90706
    - Kaiser Permanente-Bellflower
  - Costa Mesa, California, United States, 92627
    - UC Irvine Health Cancer Center-Newport
  - Duarte, California, United States, 91010
    - City of Hope Comprehensive Cancer Center
  - Fontana, California, United States, 92335
    - Kaiser Permanente-Fontana
  - Fremont, California, United States, 94538
    - Kaiser Permanente-Fremont
  - Fremont, California, United States, 94538
    - Palo Alto Medical Foundation-Fremont
  - Fresno, California, United States, 93720
    - Kaiser Permanente-Fresno
  - Harbor City, California, United States, 90710
    - Kaiser Permanente South Bay
  - Irvine, California, United States, 92618
    - Kaiser Permanente-Irvine
  - La Jolla, California, United States, 92093
    - UC San Diego Moores Cancer Center
  - Los Angeles, California, United States, 90033
    - USC / Norris Comprehensive Cancer Center
  - Los Angeles, California, United States, 90048
    - Cedars-Sinai Medical Center
  - Los Angeles, California, United States, 90095
    - UCLA / Jonsson Comprehensive Cancer Center
  - Los Angeles, California, United States, 90027
    - Kaiser Permanente Los Angeles Medical Center
  - Los Angeles, California, United States, 90034
    - Kaiser Permanente West Los Angeles
  - Los Angeles, California, United States, 90033
    - Los Angeles General Medical Center
  - Marysville, California, United States, 95901
    - Fremont - Rideout Cancer Center
  - Modesto, California, United States, 95355
    - Memorial Medical Center
  - Modesto, California, United States, 95356
    - Kaiser Permanente-Modesto
  - Mountain View, California, United States, 94040
    - Palo Alto Medical Foundation-Camino Division
  - Newport Beach, California, United States, 92663
    - USC Norris Oncology/Hematology-Newport Beach
  - Novato, California, United States, 94945
    - Sutter Cancer Research Consortium
  - Oakland, California, United States, 94611
    - Kaiser Permanente-Oakland
  - Orange, California, United States, 92868
    - UC Irvine Health/Chao Family Comprehensive Cancer Center
  - Orange, California, United States, 92868
    - Saint Joseph Hospital - Orange
  - Palo Alto, California, United States, 94304
    - Stanford Cancer Institute Palo Alto
  - Palo Alto, California, United States, 94301
    - Palo Alto Medical Foundation Health Care
  - Panorama City, California, United States, 91402
    - Kaiser Permanente - Panorama City
  - Redwood City, California, United States, 94063
    - Kaiser Permanente-Redwood City
  - Richmond, California, United States, 94801
    - Kaiser Permanente-Richmond
  - Riverside, California, United States, 92505
    - Kaiser Permanente-Riverside
  - Roseville, California, United States, 95661
    - Kaiser Permanente-Roseville
  - Roseville, California, United States, 95661
    - Sutter Roseville Medical Center
  - Sacramento, California, United States, 95816
    - Sutter Medical Center Sacramento
  - Sacramento, California, United States, 95817
    - University of California Davis Comprehensive Cancer Center
  - Sacramento, California, United States, 95823
    - Kaiser Permanente-South Sacramento
  - Sacramento, California, United States, 95825
    - Kaiser Permanente Sacramento Medical Center
  - San Diego, California, United States, 92120
    - Kaiser Permanente-San Diego Zion
  - San Diego, California, United States, 92108
    - Kaiser Permanente-San Diego Mission
  - San Francisco, California, United States, 94115
    - Kaiser Permanente-San Francisco
  - San Francisco, California, United States, 94115
    - California Pacific Medical Center-Pacific Campus
  - San Jose, California, United States, 95119
    - Kaiser Permanente-Santa Teresa-San Jose
  - San Leandro, California, United States, 94577
    - Kaiser Permanente San Leandro
  - San Marcos, California, United States, 92078
    - Kaiser Permanente-San Marcos
  - San Rafael, California, United States, 94903
    - Kaiser Permanente-San Rafael
  - Santa Clara, California, United States, 95051
    - Kaiser Permanente Medical Center - Santa Clara
  - Santa Cruz, California, United States, 95065
    - Palo Alto Medical Foundation-Santa Cruz
  - Santa Rosa, California, United States, 95403
    - Kaiser Permanente-Santa Rosa
  - Santa Rosa, California, United States, 95403
    - Sutter Pacific Medical Foundation
  - South San Francisco, California, United States, 94080
    - Kaiser Permanente-South San Francisco
  - Stockton, California, United States, 95210
    - Kaiser Permanente-Stockton
  - Sunnyvale, California, United States, 94086
    - Palo Alto Medical Foundation-Sunnyvale
  - Truckee, California, United States, 96161
    - Gene Upshaw Memorial Tahoe Forest Cancer Center
  - Vacaville, California, United States, 95688
    - Kaiser Permanente Medical Center-Vacaville
  - Vallejo, California, United States, 94589
    - Kaiser Permanente-Vallejo
  - Walnut Creek, California, United States, 94596
    - Kaiser Permanente-Walnut Creek
  - Woodland Hills, California, United States, 91367
    - Kaiser Permanente-Woodland Hills
- Colorado
  - Aurora, Colorado, United States, 80045
    - UCHealth University of Colorado Hospital
  - Colorado Springs, Colorado, United States, 80907
    - Penrose-Saint Francis Healthcare
  - Colorado Springs, Colorado, United States, 80909
    - UCHealth Memorial Hospital Central
  - Denver, Colorado, United States, 80205
    - Kaiser Permanente-Franklin
  - Denver, Colorado, United States, 80218
    - Saint Joseph Hospital - Cancer Centers of Colorado
  - Denver, Colorado, United States, 80210
    - AdventHealth Porter
  - Fort Collins, Colorado, United States, 80524
    - Poudre Valley Hospital
  - Greeley, Colorado, United States, 80631
    - Banner North Colorado Medical Center
  - Lafayette, Colorado, United States, 80026
    - Kaiser Permanente-Rock Creek
  - Littleton, Colorado, United States, 80122
    - AdventHealth Littleton
  - Lone Tree, Colorado, United States, 80124
    - Kaiser Permanente-Lone Tree
  - Parker, Colorado, United States, 80138
    - AdventHealth Parker
- Connecticut
  - Fairfield, Connecticut, United States, 06824
    - Smilow Cancer Hospital Care Center-Fairfield
  - Hartford, Connecticut, United States, 06105
    - Smilow Cancer Hospital Care Center at Saint Francis
  - New Haven, Connecticut, United States, 06520
    - Yale University
  - Stamford, Connecticut, United States, 06904
    - Stamford Hospital/Bennett Cancer Center
  - Trumbull, Connecticut, United States, 06611
    - Smilow Cancer Hospital Care Center-Trumbull
- Delaware
  - Newark, Delaware, United States, 19713
    - Helen F Graham Cancer Center
  - Newark, Delaware, United States, 19713
    - Medical Oncology Hematology Consultants PA
  - Newark, Delaware, United States, 19718
    - Christiana Care Health System-Christiana Hospital
  - Rehoboth Beach, Delaware, United States, 19971
    - Beebe Health Campus
- District of Columbia
  - Washington D.C., District of Columbia, United States, 20010
    - Medstar Washington Hospital Center
  - Washington D.C., District of Columbia, United States, 20007
    - MedStar Georgetown University Hospital
- Florida
  - Lakeland, Florida, United States, 33805
    - Lakeland Regional Health Hollis Cancer Center
  - Miami, Florida, United States, 33136
    - University of Miami Miller School of Medicine-Sylvester Cancer Center
  - Miami Beach, Florida, United States, 33140
    - Mount Sinai Medical Center
  - Orlando, Florida, United States, 32806
    - Orlando Health Cancer Institute
  - Tampa, Florida, United States, 33612
    - Moffitt Cancer Center
  - Weston, Florida, United States, 33331
    - Cleveland Clinic-Weston
- Georgia
  - Atlanta, Georgia, United States, 30322
    - Emory University Hospital/Winship Cancer Institute
  - Atlanta, Georgia, United States, 30342
    - Northside Hospital
  - Cumming, Georgia, United States, 30041
    - Northside Hospital-Forsyth
  - Savannah, Georgia, United States, 31405
    - Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
  - Savannah, Georgia, United States, 31404
    - Memorial Health University Medical Center
  - Valdosta, Georgia, United States, 31602
    - South Georgia Medical Center/Pearlman Cancer Center
- Hawaii
  - Honolulu, Hawaii, United States, 96813
    - Queen's Medical Center
  - Honolulu, Hawaii, United States, 96813
    - Hawaii Cancer Care Inc - Waterfront Plaza
  - Honolulu, Hawaii, United States, 96813
    - Queen's Cancer Cenrer - POB I
  - Honolulu, Hawaii, United States, 96813
    - Straub Clinic and Hospital
  - Honolulu, Hawaii, United States, 96813
    - University of Hawaii Cancer Center
  - Honolulu, Hawaii, United States, 96817
    - Hawaii Cancer Care Inc-Liliha
  - Honolulu, Hawaii, United States, 96817
    - Queen's Cancer Center - Kuakini
  - Honolulu, Hawaii, United States, 96813
    - Island Urology
  - Honolulu, Hawaii, United States, 96859
    - Tripler Army Medical Center
- Idaho
  - Boise, Idaho, United States, 83706
    - Saint Alphonsus Cancer Care Center-Boise
  - Boise, Idaho, United States, 83712
    - Saint Luke's Cancer Institute - Boise
  - Coeur d'Alene, Idaho, United States, 83814
    - Kootenai Health - Coeur d'Alene
  - Fruitland, Idaho, United States, 83619
    - Saint Luke's Cancer Institute - Fruitland
  - Meridian, Idaho, United States, 83642
    - Saint Luke's Cancer Institute - Meridian
  - Nampa, Idaho, United States, 83687
    - Saint Luke's Cancer Institute - Nampa
  - Post Falls, Idaho, United States, 83854
    - Kootenai Clinic Cancer Services - Post Falls
  - Sandpoint, Idaho, United States, 83864
    - Kootenai Clinic Cancer Services - Sandpoint
  - Twin Falls, Idaho, United States, 83301
    - Saint Luke's Cancer Institute - Twin Falls
- Illinois
  - Aurora, Illinois, United States, 60504
    - Rush-Copley Medical Center
  - Bloomington, Illinois, United States, 61704
    - Illinois CancerCare-Bloomington
  - Canton, Illinois, United States, 61520
    - Illinois CancerCare-Canton
  - Centralia, Illinois, United States, 62801
    - Centralia Oncology Clinic
  - Chicago, Illinois, United States, 60611
    - Northwestern University
  - Chicago, Illinois, United States, 60637
    - University of Chicago Comprehensive Cancer Center
  - Chicago, Illinois, United States, 60612
    - Rush MD Anderson Cancer Center
  - Danville, Illinois, United States, 61832
    - Carle at The Riverfront
  - Decatur, Illinois, United States, 62526
    - Decatur Memorial Hospital
  - Decatur, Illinois, United States, 62526
    - Cancer Care Specialists of Illinois - Decatur
  - Effingham, Illinois, United States, 62401
    - Crossroads Cancer Center
  - Effingham, Illinois, United States, 62401
    - Carle Physician Group-Effingham
  - Elmhurst, Illinois, United States, 60126
    - Elmhurst Memorial Hospital
  - Eureka, Illinois, United States, 61530
    - Illinois CancerCare-Eureka
  - Evanston, Illinois, United States, 60201
    - NorthShore University HealthSystem-Evanston Hospital
  - Galesburg, Illinois, United States, 61401
    - Illinois CancerCare-Galesburg
  - Geneva, Illinois, United States, 60134
    - Northwestern Medicine Cancer Center Delnor
  - Glenview, Illinois, United States, 60026
    - NorthShore University HealthSystem-Glenbrook Hospital
  - Highland Park, Illinois, United States, 60035
    - NorthShore University HealthSystem-Highland Park Hospital
  - Kewanee, Illinois, United States, 61443
    - Illinois CancerCare-Kewanee Clinic
  - Macomb, Illinois, United States, 61455
    - Illinois CancerCare-Macomb
  - Mattoon, Illinois, United States, 61938
    - Carle Physician Group-Mattoon/Charleston
  - Maywood, Illinois, United States, 60153
    - Loyola University Medical Center
  - Naperville, Illinois, United States, 60540
    - Edward Hospital/Cancer Center
  - New Lenox, Illinois, United States, 60451
    - UC Comprehensive Cancer Center at Silver Cross
  - O'Fallon, Illinois, United States, 62269
    - Cancer Care Center of O'Fallon
  - Orland Park, Illinois, United States, 60462
    - University of Chicago Medicine-Orland Park
  - Ottawa, Illinois, United States, 61350
    - Illinois CancerCare-Ottawa Clinic
  - Pekin, Illinois, United States, 61554
    - Illinois CancerCare-Pekin
  - Peoria, Illinois, United States, 61615
    - Illinois CancerCare-Peoria
  - Peru, Illinois, United States, 61354
    - Illinois CancerCare-Peru
  - Plainfield, Illinois, United States, 60585
    - Edward Hospital/Cancer Center?Plainfield
  - Princeton, Illinois, United States, 61356
    - Illinois CancerCare-Princeton
  - Rockford, Illinois, United States, 61114
    - UW Health Carbone Cancer Center Rockford
  - Springfield, Illinois, United States, 62702
    - Southern Illinois University School of Medicine
  - Springfield, Illinois, United States, 62702
    - Springfield Clinic
  - Springfield, Illinois, United States, 62702
    - Central Illinois Hematology Oncology Center
  - Springfield, Illinois, United States, 62781
    - Springfield Memorial Hospital
  - Urbana, Illinois, United States, 61801
    - Carle Cancer Center
  - Urbana, Illinois, United States, 61801
    - The Carle Foundation Hospital
  - Warrenville, Illinois, United States, 60555
    - Northwestern Medicine Cancer Center Warrenville
  - Yorkville, Illinois, United States, 60560
    - Rush-Copley Healthcare Center
- Indiana
  - Indianapolis, Indiana, United States, 46237
    - Franciscan Health Indianapolis
  - Indianapolis, Indiana, United States, 46202
    - Indiana University/Melvin and Bren Simon Cancer Center
  - Indianapolis, Indiana, United States, 46219
    - Community Cancer Center East
  - Indianapolis, Indiana, United States, 46227
    - Community Cancer Center South
  - Indianapolis, Indiana, United States, 46256
    - Community Cancer Center North
  - Mooresville, Indiana, United States, 46158
    - Franciscan Health Mooresville
  - Richmond, Indiana, United States, 47374
    - Reid Health
- Iowa
  - Ames, Iowa, United States, 50010
    - Mary Greeley Medical Center
  - Ames, Iowa, United States, 50010
    - McFarland Clinic - Ames
  - Boone, Iowa, United States, 50036
    - McFarland Clinic - Boone
  - Cedar Rapids, Iowa, United States, 52402
    - Physicians' Clinic of Iowa PC
  - Clive, Iowa, United States, 50325
    - Mercy Cancer Center-West Lakes
  - Clive, Iowa, United States, 50325
    - UI Health Care Mission Cancer and Blood - West Des Moines Clinic
  - Des Moines, Iowa, United States, 50309
    - Iowa Methodist Medical Center
  - Des Moines, Iowa, United States, 50314
    - Mercy Medical Center - Des Moines
  - Des Moines, Iowa, United States, 50309
    - UI Health Care Mission Cancer and Blood - Des Moines Clinic
  - Des Moines, Iowa, United States, 50314
    - UI Health Care Mission Cancer and Blood - Laurel Clinic
  - Fort Dodge, Iowa, United States, 50501
    - McFarland Clinic - Trinity Cancer Center
  - Iowa City, Iowa, United States, 52242
    - University of Iowa/Holden Comprehensive Cancer Center
  - Jefferson, Iowa, United States, 50129
    - McFarland Clinic - Jefferson
  - Marshalltown, Iowa, United States, 50158
    - McFarland Clinic - Marshalltown
  - West Des Moines, Iowa, United States, 50266
    - Mercy Medical Center-West Lakes
- Kansas
  - Chanute, Kansas, United States, 66720
    - Cancer Center of Kansas - Chanute
  - Dodge City, Kansas, United States, 67801
    - Cancer Center of Kansas - Dodge City
  - El Dorado, Kansas, United States, 67042
    - Cancer Center of Kansas - El Dorado
  - Garden City, Kansas, United States, 67846
    - Saint Catherine Hospital
  - Great Bend, Kansas, United States, 67530
    - Central Care Cancer Center - Great Bend
  - Great Bend, Kansas, United States, 67530
    - Saint Rose Ambulatory and Surgery Center
  - Hays, Kansas, United States, 67601
    - HaysMed
  - Kansas City, Kansas, United States, 66160
    - University of Kansas Cancer Center
  - Kansas City, Kansas, United States, 66112
    - University of Kansas Cancer Center-West
  - Lawrence, Kansas, United States, 66044
    - Lawrence Memorial Hospital
  - Lenexa, Kansas, United States, 66219
    - Kansas Institute of Medicine Cancer and Blood Center
  - Lenexa, Kansas, United States, 66219
    - Minimally Invasive Surgery Hospital
  - Liberal, Kansas, United States, 67905
    - Cancer Center of Kansas-Liberal
  - McPherson, Kansas, United States, 67460
    - Cancer Center of Kansas - McPherson
  - Newton, Kansas, United States, 67114
    - Cancer Center of Kansas - Newton
  - Olathe, Kansas, United States, 66061
    - The University of Kansas Cancer Center - Olathe
  - Overland Park, Kansas, United States, 66210
    - University of Kansas Cancer Center-Overland Park
  - Overland Park, Kansas, United States, 66209
    - Menorah Medical Center
  - Overland Park, Kansas, United States, 66213
    - Saint Luke's South Hospital
  - Parsons, Kansas, United States, 67357
    - Cancer Center of Kansas - Parsons
  - Pittsburg, Kansas, United States, 66762
    - Mercy Hospital Pittsburg
  - Salina, Kansas, United States, 67401
    - Salina Regional Health Center
  - Salina, Kansas, United States, 67401
    - Cancer Center of Kansas - Salina
  - Topeka, Kansas, United States, 66606
    - University of Kansas Health System Saint Francis Campus
  - Wellington, Kansas, United States, 67152
    - Cancer Center of Kansas - Wellington
  - Wichita, Kansas, United States, 67214
    - Ascension Via Christi Hospitals Wichita
  - Wichita, Kansas, United States, 67208
    - Cancer Center of Kansas-Wichita Medical Arts Tower
  - Wichita, Kansas, United States, 67214
    - Cancer Center of Kansas - Wichita
  - Winfield, Kansas, United States, 67156
    - Cancer Center of Kansas - Winfield
- Kentucky
  - Bardstown, Kentucky, United States, 40004
    - Flaget Memorial Hospital
  - Lexington, Kentucky, United States, 40504
    - Saint Joseph Radiation Oncology Resource Center
  - Lexington, Kentucky, United States, 40509
    - Saint Joseph Hospital East
  - Louisville, Kentucky, United States, 40245
    - UofL Health Medical Center Northeast
  - Louisville, Kentucky, United States, 40215
    - Saints Mary and Elizabeth Hospital
  - Owensboro, Kentucky, United States, 42303
    - Owensboro Health Mitchell Memorial Cancer Center
- Louisiana
  - Baton Rouge, Louisiana, United States, 70805
    - LSU Health Baton Rouge-North Clinic
  - Baton Rouge, Louisiana, United States, 70809
    - Louisiana Hematology Oncology Associates LLC
  - Baton Rouge, Louisiana, United States, 70809
    - Mary Bird Perkins Cancer Center
  - Baton Rouge, Louisiana, United States, 70808
    - Our Lady of the Lake Physician Group
  - Covington, Louisiana, United States, 70433
    - Northshore Oncology Associates-Covington
  - Monroe, Louisiana, United States, 71202
    - Ochsner LSU Health Monroe Medical Center
  - Shreveport, Louisiana, United States, 71103
    - LSU Health Sciences Center at Shreveport
- Maine
  - Augusta, Maine, United States, 04330
    - Harold Alfond Center for Cancer Care
  - Bangor, Maine, United States, 04401
    - Eastern Maine Medical Center
  - Brewer, Maine, United States, 04412
    - Lafayette Family Cancer Center-EMMC
  - Westbrook, Maine, United States, 04092
    - New England Cancer Specialists
- Maryland
  - Baltimore, Maryland, United States, 21237
    - MedStar Franklin Square Medical Center/Weinberg Cancer Institute
  - Baltimore, Maryland, United States, 21202
    - Mercy Medical Center
  - Frederick, Maryland, United States, 21701
    - Frederick Memorial Hospital
- Massachusetts
  - Beverly, Massachusetts, United States, 01915
    - Beverly Hospital
  - Boston, Massachusetts, United States, 02215
    - Beth Israel Deaconess Medical Center
  - Boston, Massachusetts, United States, 02215
    - Dana-Farber Cancer Institute
  - Boston, Massachusetts, United States, 02118
    - Boston Medical Center
  - Boston, Massachusetts, United States, 02114
    - Massachusetts General Hospital Cancer Center
  - Burlington, Massachusetts, United States, 01805
    - Lahey Hospital and Medical Center
  - Gloucester, Massachusetts, United States, 01930
    - Addison Gilbert Hospital
  - Springfield, Massachusetts, United States, 01199
    - Baystate Medical Center
- Michigan
  - Ann Arbor, Michigan, United States, 48109
    - University of Michigan Rogel Cancer Center
  - Detroit, Michigan, United States, 48202
    - Henry Ford Hospital
  - Detroit, Michigan, United States, 48201
    - Wayne State University/Karmanos Cancer Institute
  - Detroit, Michigan, United States, 48236
    - Henry Ford Health Saint John Hospital
  - East China Township, Michigan, United States, 48054
    - Henry Ford River District Hospital
  - Escanaba, Michigan, United States, 49829
    - OSF Saint Francis Hospital and Medical Group
  - Flint, Michigan, United States, 48503
    - Hurley Medical Center
  - Flint, Michigan, United States, 48503
    - Genesys Hurley Cancer Institute
  - Grand Rapids, Michigan, United States, 49503
    - Trinity Health Grand Rapids Hospital
  - Grand Rapids, Michigan, United States, 49503
    - Corewell Health Grand Rapids Hospitals - Butterworth Hospital
  - Grosse Pointe Woods, Michigan, United States, 48236
    - Henry Ford Saint John Hospital - Academic
  - Grosse Pointe Woods, Michigan, United States, 48236
    - Henry Ford Saint John Hospital - Breast
  - Grosse Pointe Woods, Michigan, United States, 48236
    - Henry Ford Saint John Hospital - Van Elslander
  - Jackson, Michigan, United States, 49201
    - Allegiance Health
  - Kalamazoo, Michigan, United States, 49007
    - West Michigan Cancer Center
  - Lansing, Michigan, United States, 48912
    - University of Michigan Health - Sparrow Lansing
  - Macomb, Michigan, United States, 48044
    - Henry Ford Warren Hospital - Breast Macomb
  - Macomb, Michigan, United States, 48044
    - Henry Ford Saint John Hospital - Macomb Medical
  - Muskegon, Michigan, United States, 49444
    - Trinity Health Muskegon Hospital
  - Reed City, Michigan, United States, 49677
    - Corewell Health Reed City Hospital
  - Rochester Hills, Michigan, United States, 48309
    - Henry Ford Rochester Hospital
  - Saginaw, Michigan, United States, 48601
    - MyMichigan Medical Center Saginaw
  - Traverse City, Michigan, United States, 49684
    - Munson Medical Center
  - Warren, Michigan, United States, 48093
    - Henry Ford Health Warren Hospital
  - Warren, Michigan, United States, 48093
    - Henry Ford Warren Hospital - GLCMS
  - Wyoming, Michigan, United States, 49519
    - University of Michigan Health - West
- Minnesota
  - Bemidji, Minnesota, United States, 56601
    - Sanford Joe Lueken Cancer Center
  - Burnsville, Minnesota, United States, 55337
    - Fairview Ridges Hospital
  - Coon Rapids, Minnesota, United States, 55433
    - Mercy Hospital
  - Duluth, Minnesota, United States, 55805
    - Essentia Health Cancer Center
  - Duluth, Minnesota, United States, 55805
    - Essentia Health Saint Mary's Medical Center
  - Duluth, Minnesota, United States, 55805
    - Miller-Dwan Hospital
  - Edina, Minnesota, United States, 55435
    - Fairview Southdale Hospital
  - Fergus Falls, Minnesota, United States, 56537
    - Lake Region Healthcare Corporation-Cancer Care
  - Fridley, Minnesota, United States, 55432
    - Unity Hospital
  - Maplewood, Minnesota, United States, 55109
    - Saint John's Hospital - Healtheast
  - Maplewood, Minnesota, United States, 55109
    - Minnesota Oncology Hematology PA-Maplewood
  - Minneapolis, Minnesota, United States, 55415
    - Hennepin County Medical Center
  - Minneapolis, Minnesota, United States, 55407
    - Abbott-Northwestern Hospital
  - Saint Louis Park, Minnesota, United States, 55416
    - Park Nicollet Clinic - Saint Louis Park
  - Saint Paul, Minnesota, United States, 55101
    - Regions Hospital
  - Saint Paul, Minnesota, United States, 55102
    - United Hospital
  - Waconia, Minnesota, United States, 55387
    - Ridgeview Medical Center
  - Woodbury, Minnesota, United States, 55125
    - Minnesota Oncology Hematology PA-Woodbury
- Mississippi
  - Jackson, Mississippi, United States, 39216
    - University of Mississippi Medical Center
- Missouri
  - Bonne Terre, Missouri, United States, 63628
    - Parkland Health Center-Bonne Terre
  - Cape Girardeau, Missouri, United States, 63703
    - Saint Francis Medical Center
  - Cape Girardeau, Missouri, United States, 63703
    - Mercy Cancer Center - Cape Girardeau
  - Independence, Missouri, United States, 64057
    - Centerpoint Medical Center LLC
  - Jefferson City, Missouri, United States, 65109
    - MU Health Care Goldschmidt Cancer Center
  - Kansas City, Missouri, United States, 64128
    - Kansas City Veterans Affairs Medical Center
  - Kansas City, Missouri, United States, 64154
    - University of Kansas Cancer Center - North
  - Kansas City, Missouri, United States, 64131
    - The University of Kansas Cancer Center-South
  - Kansas City, Missouri, United States, 64111
    - Saint Luke's Hospital of Kansas City
  - Kansas City, Missouri, United States, 64132
    - Research Medical Center
  - Kansas City, Missouri, United States, 64118
    - Heartland Hematology and Oncology Associates Incorporated
  - Kansas City, Missouri, United States, 64108
    - University Health Truman Medical Center
  - Lee's Summit, Missouri, United States, 64064
    - University of Kansas Cancer Center - Lee's Summit
  - Lee's Summit, Missouri, United States, 64086
    - Saint Luke's East - Lee's Summit
  - Liberty, Missouri, United States, 64068
    - Liberty Hospital
  - Saint Joseph, Missouri, United States, 64506
    - Heartland Regional Medical Center
  - Sainte Genevieve, Missouri, United States, 63670
    - Sainte Genevieve County Memorial Hospital
  - Springfield, Missouri, United States, 65807
    - CoxHealth South Hospital
  - Springfield, Missouri, United States, 65804
    - Mercy Hospital Springfield
  - St Louis, Missouri, United States, 63131
    - Missouri Baptist Medical Center
  - Sullivan, Missouri, United States, 63080
    - Missouri Baptist Sullivan Hospital
- Montana
  - Anaconda, Montana, United States, 59711
    - Community Hospital of Anaconda
  - Billings, Montana, United States, 59101
    - Billings Clinic Cancer Center
  - Billings, Montana, United States, 59101
    - Saint Vincent Healthcare
  - Bozeman, Montana, United States, 59715
    - Bozeman Health Deaconess Hospital
  - Butte, Montana, United States, 59701
    - Saint James Community Hospital and Cancer Treatment Center
  - Great Falls, Montana, United States, 59405
    - Great Falls Clinic
  - Great Falls, Montana, United States, 59405
    - Benefis Sletten Cancer Institute
  - Helena, Montana, United States, 59601
    - Saint Peter's Community Hospital
  - Kalispell, Montana, United States, 59901
    - Logan Health Medical Center
  - Missoula, Montana, United States, 59802
    - Saint Patrick Hospital - Community Hospital
  - Missoula, Montana, United States, 59804
    - Community Medical Center
- Nebraska
  - Grand Island, Nebraska, United States, 68803
    - Nebraska Cancer Specialists/Oncology Hematology West PC
  - Lincoln, Nebraska, United States, 68506
    - Nebraska Hematology and Oncology
  - Lincoln, Nebraska, United States, 68516
    - Cancer Partners of Nebraska
  - Norfolk, Nebraska, United States, 68701
    - Faith Regional Health Services Carson Cancer Center
  - Omaha, Nebraska, United States, 68114
    - Nebraska Methodist Hospital
  - Omaha, Nebraska, United States, 68124
    - Alegent Health Bergan Mercy Medical Center
  - Omaha, Nebraska, United States, 68122
    - Alegent Health Immanuel Medical Center
  - Omaha, Nebraska, United States, 68130
    - Alegent Health Lakeside Hospital
  - Omaha, Nebraska, United States, 68131
    - Creighton University Medical Center
  - Omaha, Nebraska, United States, 68124
    - Nebraska Cancer Specialists - Omaha
  - Scottsbluff, Nebraska, United States, 69361
    - Regional West Medical Center Cancer Center
- Nevada
  - Henderson, Nevada, United States, 89052
    - Comprehensive Cancer Centers of Nevada - Henderson
  - Henderson, Nevada, United States, 89052
    - Cancer and Blood Specialists-Henderson
  - Henderson, Nevada, United States, 89052
    - Las Vegas Cancer Center-Henderson
  - Henderson, Nevada, United States, 89074
    - Comprehensive Cancer Centers of Nevada-Southeast Henderson
  - Henderson, Nevada, United States, 89074
    - Oncology Las Vegas - Henderson
  - Las Vegas, Nevada, United States, 89128
    - Comprehensive Cancer Centers of Nevada - Northwest
  - Las Vegas, Nevada, United States, 89148
    - Comprehensive Cancer Centers of Nevada
  - Las Vegas, Nevada, United States, 89169
    - Comprehensive Cancer Centers of Nevada - Central Valley
  - Las Vegas, Nevada, United States, 89102
    - University Medical Center of Southern Nevada
  - Las Vegas, Nevada, United States, 89121
    - Cancer Therapy and Integrative Medicine
  - Las Vegas, Nevada, United States, 89148-2405
    - Las Vegas Cancer Center-Medical Center
  - Las Vegas, Nevada, United States, 89128
    - Ann M Wierman MD LTD
  - Las Vegas, Nevada, United States, 89169
    - University Cancer Center
  - Las Vegas, Nevada, United States, 89183
    - OptumCare Cancer Care at Fort Apache
- New Hampshire
  - Dover, New Hampshire, United States, 03820
    - Wentworth-Douglass Hospital
  - Lebanon, New Hampshire, United States, 03756
    - Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
  - Manchester, New Hampshire, United States, 03104
    - Dartmouth Cancer Center - Manchester/ DCC Manchester
  - Nashua, New Hampshire, United States, 03060
    - Saint Joseph Hospital
  - Nashua, New Hampshire, United States, 03063
    - Dartmouth Cancer Center - Nashua
- New Jersey
  - East Orange, New Jersey, United States, 07018-1095
    - Veterans Adminstration New Jersey Health Care System
  - Hackensack, New Jersey, United States, 07601
    - Hackensack University Medical Center
  - Livingston, New Jersey, United States, 07039
    - Saint Barnabas Medical Center
  - New Brunswick, New Jersey, United States, 08903
    - Rutgers Cancer Institute of New Jersey
- New Mexico
  - Albuquerque, New Mexico, United States, 87102
    - Lovelace Medical Center-Saint Joseph Square
  - Albuquerque, New Mexico, United States, 87106
    - Southwest Gynecologic Oncology Associates Inc
  - Albuquerque, New Mexico, United States, 87106
    - University of New Mexico Cancer Center
- New York
  - Auburn, New York, United States, 13021
    - Hematology Oncology Associates of Central New York-Auburn
  - Buffalo, New York, United States, 14263
    - Roswell Park Cancer Institute
  - Camillus, New York, United States, 13031
    - Hematology Oncology Associates of CNY at Camillus
  - East Syracuse, New York, United States, 13057
    - Hematology Oncology Associates of Central New York-East Syracuse
  - Glens Falls, New York, United States, 12801
    - Glens Falls Hospital
  - New York, New York, United States, 10032
    - NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
  - Rochester, New York, United States, 14642
    - University of Rochester
  - Rochester, New York, United States, 14621
    - Rochester General Hospital
  - Stony Brook, New York, United States, 11794
    - Stony Brook University Medical Center
  - Syracuse, New York, United States, 13210
    - State University of New York Upstate Medical University
- North Carolina
  - Chapel Hill, North Carolina, United States, 27599
    - UNC Lineberger Comprehensive Cancer Center
  - Clinton, North Carolina, United States, 28328
    - Southeastern Medical Oncology Center-Clinton
  - Durham, North Carolina, United States, 27710
    - Duke University Medical Center
  - Goldsboro, North Carolina, United States, 27534
    - Southeastern Medical Oncology Center-Goldsboro
  - Goldsboro, North Carolina, United States, 27534
    - Wayne Memorial Hospital
  - Hendersonville, North Carolina, United States, 28791
    - Margaret R Pardee Memorial Hospital
  - Jacksonville, North Carolina, United States, 28546
    - Southeastern Medical Oncology Center-Jacksonville
- North Dakota
  - Bismarck, North Dakota, United States, 58501
    - Sanford Bismarck Medical Center
  - Fargo, North Dakota, United States, 58122
    - Sanford Roger Maris Cancer Center
  - Fargo, North Dakota, United States, 58122
    - Sanford Broadway Medical Center
  - Grand Forks, North Dakota, United States, 58201
    - Altru Cancer Center
- Ohio
  - Beachwood, Ohio, United States, 44122
    - UHHS-Chagrin Highlands Medical Center
  - Belpre, Ohio, United States, 45714
    - Strecker Cancer Center-Belpre
  - Centerville, Ohio, United States, 45459
    - Miami Valley Hospital South
  - Centerville, Ohio, United States, 45459
    - Dayton Physicians LLC-Miami Valley South
  - Chillicothe, Ohio, United States, 45601
    - Adena Regional Medical Center
  - Cincinnati, Ohio, United States, 45219
    - University of Cincinnati Cancer Center-UC Medical Center
  - Cleveland, Ohio, United States, 44106
    - Case Western Reserve University
  - Cleveland, Ohio, United States, 44109
    - MetroHealth Medical Center
  - Cleveland, Ohio, United States, 44195
    - Cleveland Clinic Foundation
  - Cleveland, Ohio, United States, 44111
    - Cleveland Clinic Cancer Center/Fairview Hospital
  - Columbus, Ohio, United States, 43214
    - Riverside Methodist Hospital
  - Columbus, Ohio, United States, 43210
    - Ohio State University Comprehensive Cancer Center
  - Columbus, Ohio, United States, 43219
    - The Mark H Zangmeister Center
  - Columbus, Ohio, United States, 43214
    - Columbus Oncology and Hematology Associates Inc
  - Columbus, Ohio, United States, 43228
    - Doctors Hospital
  - Columbus, Ohio, United States, 43213
    - Mount Carmel East Hospital
  - Columbus, Ohio, United States, 43215
    - Grant Medical Center
  - Columbus, Ohio, United States, 43222
    - Mount Carmel Health Center West
  - Dayton, Ohio, United States, 45406
    - Good Samaritan Hospital - Dayton
  - Dayton, Ohio, United States, 45409
    - Miami Valley Hospital
  - Dayton, Ohio, United States, 45415
    - Miami Valley Hospital North
  - Dayton, Ohio, United States, 45415
    - Dayton Physician LLC - Englewood
  - Delaware, Ohio, United States, 43015
    - Delaware Health Center-Grady Cancer Center
  - Delaware, Ohio, United States, 43015
    - Grady Memorial Hospital
  - Findlay, Ohio, United States, 45840
    - Blanchard Valley Hospital
  - Findlay, Ohio, United States, 45840
    - Armes Family Cancer Center
  - Findlay, Ohio, United States, 45840
    - Orion Cancer Care
  - Independence, Ohio, United States, 44131
    - Cleveland Clinic Cancer Center Independence
  - Kettering, Ohio, United States, 45429
    - Kettering Medical Center
  - Kettering, Ohio, United States, 45409
    - Greater Dayton Cancer Center
  - Mansfield, Ohio, United States, 44906
    - Cleveland Clinic Cancer Center Mansfield
  - Mansfield, Ohio, United States, 44903
    - OhioHealth Mansfield Hospital
  - Marietta, Ohio, United States, 45750
    - Marietta Memorial Hospital
  - Marion, Ohio, United States, 43302
    - OhioHealth Marion General Hospital
  - Mayfield Heights, Ohio, United States, 44124
    - Hillcrest Hospital Cancer Center
  - Mount Vernon, Ohio, United States, 43050
    - Knox Community Hospital
  - Newark, Ohio, United States, 43055
    - Licking Memorial Hospital
  - Parma, Ohio, United States, 44129
    - University Hospitals Parma Medical Center
  - Portsmouth, Ohio, United States, 45662
    - Southern Ohio Medical Center
  - Sandusky, Ohio, United States, 44870
    - North Coast Cancer Care
  - Sandusky, Ohio, United States, 44870
    - UH Seidman Cancer Center at Firelands Regional Medical Center
  - Strongsville, Ohio, United States, 44136
    - Cleveland Clinic Cancer Center Strongsville
  - Sylvania, Ohio, United States, 43560
    - ProMedica Flower Hospital
  - Toledo, Ohio, United States, 43614
    - University of Toledo
  - Warrensville Heights, Ohio, United States, 44122
    - South Pointe Hospital
  - Westerville, Ohio, United States, 43081
    - Saint Ann's Hospital
  - Wooster, Ohio, United States, 44691
    - Cleveland Clinic Wooster Family Health and Surgery Center
  - Zanesville, Ohio, United States, 43701
    - Genesis Healthcare System Cancer Care Center
- Oklahoma
  - Oklahoma City, Oklahoma, United States, 73104
    - University of Oklahoma Health Sciences Center
  - Oklahoma City, Oklahoma, United States, 73120
    - Mercy Hospital Oklahoma City
- Oregon
  - Portland, Oregon, United States, 97239
    - Oregon Health and Science University
  - Portland, Oregon, United States, 97213
    - Providence Portland Medical Center
  - Portland, Oregon, United States, 97227
    - Kaiser Permanente Northwest
- Pennsylvania
  - Abington, Pennsylvania, United States, 19001
    - Jefferson Abington Hospital
  - Allentown, Pennsylvania, United States, 18103
    - Lehigh Valley Hospital-Cedar Crest
  - Bethlehem, Pennsylvania, United States, 18015
    - Saint Luke's University Hospital-Bethlehem Campus
  - Danville, Pennsylvania, United States, 17822
    - Geisinger Medical Center
  - Ephrata, Pennsylvania, United States, 17522
    - Ephrata Cancer Center
  - Ephrata, Pennsylvania, United States, 17522
    - Ephrata Community Hospital
  - Erie, Pennsylvania, United States, 16505
    - UPMC Hillman Cancer Center Erie
  - Gettysburg, Pennsylvania, United States, 17325
    - Adams Cancer Center
  - Hanover, Pennsylvania, United States, 17331
    - WellSpan Medical Oncology and Hematology
  - Hazleton, Pennsylvania, United States, 18201
    - Geisinger Medical Center-Cancer Center Hazleton
  - Hershey, Pennsylvania, United States, 17033-0850
    - Penn State Milton S Hershey Medical Center
  - Philadelphia, Pennsylvania, United States, 19111
    - Fox Chase Cancer Center
  - Pittsburgh, Pennsylvania, United States, 15212
    - Allegheny General Hospital
  - Pittsburgh, Pennsylvania, United States, 15224
    - West Penn Hospital
  - Pittsburgh, Pennsylvania, United States, 15232
    - University of Pittsburgh Cancer Institute (UPCI)
  - Pottsville, Pennsylvania, United States, 17901
    - Geisinger Cancer Services-Pottsville
  - West Reading, Pennsylvania, United States, 19611
    - Reading Hospital
  - Wexford, Pennsylvania, United States, 15090
    - Wexford Health and Wellness Pavilion
  - Wilkes-Barre, Pennsylvania, United States, 18711
    - Geisinger Wyoming Valley/Henry Cancer Center
  - Williamsport, Pennsylvania, United States, 17701
    - UPMC Susquehanna
  - York, Pennsylvania, United States, 17403
    - WellSpan Health-York Cancer Center
  - York, Pennsylvania, United States, 17403
    - WellSpan Health-York Hospital
- Rhode Island
  - Newport, Rhode Island, United States, 02840
    - Newport Hospital
  - Providence, Rhode Island, United States, 02903
    - Rhode Island Hospital
  - Providence, Rhode Island, United States, 02906
    - Miriam Hospital
- South Carolina
  - Anderson, South Carolina, United States, 29621
    - AnMed Health Cancer Center
  - Charleston, South Carolina, United States, 29401
    - Roper Hospital
  - Charleston, South Carolina, United States, 29406
    - Lowcountry Hematology Oncology PA-North Charleston
  - Charleston, South Carolina, United States, 29414
    - Bon Secours Saint Francis Hospital
  - Charleston, South Carolina, United States, 29403
    - Charleston Oncology - Roper
  - Charleston, South Carolina, United States, 29414
    - Charleston Oncology - Saint Francis
  - Charleston, South Carolina, United States, 29414
    - Lowcountry Oncology Associates - West Ashley
  - Greenville, South Carolina, United States, 29607
    - Saint Francis Cancer Center
  - Mt. Pleasant, South Carolina, United States, 29464
    - Lowcountry Oncology Associates - Mount Pleasant
- South Dakota
  - Rapid City, South Dakota, United States, 57701
    - Rapid City Regional Hospital
  - Sioux Falls, South Dakota, United States, 57117-5134
    - Sanford USD Medical Center - Sioux Falls
  - Sioux Falls, South Dakota, United States, 57104
    - Sanford Cancer Center Oncology Clinic
- Tennessee
  - Germantown, Tennessee, United States, 38138
    - The West Clinic - Wolf River
  - Memphis, Tennessee, United States, 38163
    - University of Tennessee Health Science Center
  - Memphis, Tennessee, United States, 38104
    - The West Clinic - Mid-Town
  - Nashville, Tennessee, United States, 37232
    - Vanderbilt University/Ingram Cancer Center
- Texas
  - Austin, Texas, United States, 78731
    - Texas Oncology - Central Austin Cancer Center
  - Dallas, Texas, United States, 75246
    - Baylor University Medical Center
  - Houston, Texas, United States, 77030
    - M D Anderson Cancer Center
- Utah
  - American Fork, Utah, United States, 84003
    - American Fork Hospital / Huntsman Intermountain Cancer Center
  - Cedar City, Utah, United States, 84720
    - Sandra L Maxwell Cancer Center
  - Logan, Utah, United States, 84321
    - Logan Regional Hospital
  - Murray, Utah, United States, 84107
    - Intermountain Medical Center
  - Ogden, Utah, United States, 84403
    - McKay-Dee Hospital Center
  - Provo, Utah, United States, 84604
    - Utah Valley Regional Medical Center
  - Salt Lake City, Utah, United States, 84112
    - Huntsman Cancer Institute/University of Utah
  - Salt Lake City, Utah, United States, 84106
    - Utah Cancer Specialists-Salt Lake City
  - Salt Lake City, Utah, United States, 84143
    - LDS Hospital
  - South Jordan, Utah, United States, 84009
    - South Jordan Health Center
  - St. George, Utah, United States, 84770
    - Saint George Regional Medical Center
- Vermont
  - Berlin Corners, Vermont, United States, 05602
    - Central Vermont Medical Center/National Life Cancer Treatment
  - Burlington, Vermont, United States, 05401
    - University of Vermont Medical Center
  - Burlington, Vermont, United States, 05405
    - University of Vermont and State Agricultural College
- Virginia
  - Lynchburg, Virginia, United States, 24501
    - Centra Alan B Pearson Regional Cancer Center
  - Richmond, Virginia, United States, 23229
    - Virginia Cancer Institute
  - Richmond, Virginia, United States, 23298
    - VCU Massey Comprehensive Cancer Center
  - South Hill, Virginia, United States, 23970
    - VCU Community Memorial Health Center
- Washington
  - Aberdeen, Washington, United States, 98520
    - Providence Regional Cancer System-Aberdeen
  - Centralia, Washington, United States, 98531
    - Providence Regional Cancer System-Centralia
  - Everett, Washington, United States, 98201
    - Providence Regional Cancer Partnership
  - Lacey, Washington, United States, 98503
    - Providence Regional Cancer System-Lacey
  - Longview, Washington, United States, 98632
    - PeaceHealth Saint John Medical Center
  - Seattle, Washington, United States, 98122
    - Swedish Medical Center-First Hill
  - Seattle, Washington, United States, 98112
    - Kaiser Permanente Washington
  - Shelton, Washington, United States, 98584
    - Providence Regional Cancer System-Shelton
  - Vancouver, Washington, United States, 98664
    - PeaceHealth Southwest Medical Center
  - Walla Walla, Washington, United States, 99362
    - Providence Saint Mary Regional Cancer Center
  - Yelm, Washington, United States, 98597
    - Providence Regional Cancer System-Yelm
- West Virginia
  - Bridgeport, West Virginia, United States, 26330
    - United Hospital Center
  - Charleston, West Virginia, United States, 25304
    - West Virginia University Charleston Division
  - Morgantown, West Virginia, United States, 26506
    - West Virginia University Healthcare
  - Parkersburg, West Virginia, United States, 26101
    - Camden Clark Medical Center
- Wisconsin
  - Antigo, Wisconsin, United States, 54409
    - Langlade Hospital and Cancer Center
  - Burlington, Wisconsin, United States, 53105
    - Aurora Cancer Care-Southern Lakes VLCC
  - Chippewa Falls, Wisconsin, United States, 54729
    - Marshfield Clinic-Chippewa Center
  - Eau Claire, Wisconsin, United States, 54701
    - Marshfield Clinic Cancer Center at Sacred Heart
  - Fond du Lac, Wisconsin, United States, 54937
    - Aurora Health Center-Fond du Lac
  - Fond du Lac, Wisconsin, United States, 54935
    - Saint Agnes Hospital/Agnesian Cancer Center
  - Germantown, Wisconsin, United States, 53022
    - Aurora Health Care Germantown Health Center
  - Grafton, Wisconsin, United States, 53024
    - Aurora Cancer Care-Grafton
  - Green Bay, Wisconsin, United States, 54311
    - Aurora BayCare Medical Center
  - Green Bay, Wisconsin, United States, 54301
    - Saint Vincent Hospital Cancer Center Green Bay
  - Green Bay, Wisconsin, United States, 54303
    - Saint Vincent Hospital Cancer Center at Saint Mary's
  - Green Bay, Wisconsin, United States, 54301-3526
    - Green Bay Oncology at Saint Vincent Hospital
  - Kenosha, Wisconsin, United States, 53142
    - Aurora Cancer Care-Kenosha South
  - La Crosse, Wisconsin, United States, 54601
    - Gundersen Lutheran Medical Center
  - Madison, Wisconsin, United States, 53792
    - University of Wisconsin Carbone Cancer Center - University Hospital
  - Marinette, Wisconsin, United States, 54143
    - Aurora Bay Area Medical Group-Marinette
  - Marinette, Wisconsin, United States, 54143
    - Bay Area Medical Center
  - Marshfield, Wisconsin, United States, 54449
    - Marshfield Medical Center-Marshfield
  - Menomonee Falls, Wisconsin, United States, 53051
    - Froedtert Menomonee Falls Hospital
  - Milwaukee, Wisconsin, United States, 53226
    - Medical College of Wisconsin
  - Milwaukee, Wisconsin, United States, 53209
    - Aurora Cancer Care-Milwaukee
  - Milwaukee, Wisconsin, United States, 53215
    - Aurora Saint Luke's Medical Center
  - Milwaukee, Wisconsin, United States, 53233
    - Aurora Sinai Medical Center
  - Milwaukee, Wisconsin, United States, 53210
    - Ascension Southeast Wisconsin Hospital - Saint Joseph Campus
  - Minocqua, Wisconsin, United States, 54548
    - Marshfield Medical Center - Minocqua
  - New Richmond, Wisconsin, United States, 54017
    - Cancer Center of Western Wisconsin
  - Oconto Falls, Wisconsin, United States, 54154
    - Saint Vincent Hospital Cancer Center at Oconto Falls
  - Oshkosh, Wisconsin, United States, 54904
    - Vince Lombardi Cancer Clinic - Oshkosh
  - Racine, Wisconsin, United States, 53406
    - Aurora Cancer Care-Racine
  - Rice Lake, Wisconsin, United States, 54868
    - Marshfield Medical Center-Rice Lake
  - Rice Lake, Wisconsin, United States, 54868
    - Lakeview Medical Center-Marshfield Clinic
  - Sheboygan, Wisconsin, United States, 53081
    - Vince Lombardi Cancer Clinic-Sheboygan
  - Sheboygan, Wisconsin, United States, 53081
    - HSHS Saint Nicholas Hospital
  - Stevens Point, Wisconsin, United States, 54481
    - Aspirus Cancer Care - Stevens Point
  - Sturgeon Bay, Wisconsin, United States, 54235-1495
    - Saint Vincent Hospital Cancer Center at Sturgeon Bay
  - Summit, Wisconsin, United States, 53066
    - Aurora Medical Center in Summit
  - Two Rivers, Wisconsin, United States, 54241
    - Vince Lombardi Cancer Clinic-Two Rivers
  - Wausau, Wisconsin, United States, 54401
    - Aspirus Regional Cancer Center
  - Wausau, Wisconsin, United States, 54401
    - Marshfield Clinic-Wausau Center
  - Wauwatosa, Wisconsin, United States, 53226
    - Aurora Cancer Care-Milwaukee West
  - West Allis, Wisconsin, United States, 53227
    - Aurora West Allis Medical Center
  - Weston, Wisconsin, United States, 54476
    - Marshfield Medical Center - Weston
  - Wisconsin Rapids, Wisconsin, United States, 54494
    - Aspirus Cancer Care - Wisconsin Rapids
  - Wisconsin Rapids, Wisconsin, United States, 54494
    - Marshfield Clinic - Wisconsin Rapids Center
- Wyoming
  - Cody, Wyoming, United States, 82414
    - Big Horn Basin Cancer Center
  - Cody, Wyoming, United States, 82414
    - Billings Clinic-Cody
  - Sheridan, Wyoming, United States, 82801
    - Welch Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Description

Inclusion Criteria:

STEP 1 REGISTRATION:
Patients must have completely resected melanoma of cutaneous origin or of unknown primary in order to be eligible for this study; patients must be classified as stage IIIA (N2a), IIIB, IIIC, or stage IV melanoma; patients with non-ulcerated T1b N1a disease are not eligible; patients with melanoma of mucosal or other non-cutaneous origin are eligible; patients with melanoma of ocular origin are not eligible; patients with a history of brain metastases are ineligible
Patients are eligible for this trial either at initial presentation of their melanoma or at the time of the first detected nodal, satellite/in-transit, distant metastases, or recurrent disease in prior lymphadenectomy basin or distant site; nodal, satellite/in-transit metastasis, distant metastases or disease in a prior complete lymphadenectomy basin must have been confirmed histologically by hematoxylin and eosin (H & E) stained slides
Patients with multiple regional nodal basin involvement are eligible; gross or microscopic extracapsular nodal extension is permitted
Patients at initial presentation of melanoma must undergo an adequate wide excision of the primary lesion, if present; patients with previously diagnosed melanoma must have had all current disease resected with pathologically negative margins and must have no evidence of disease at the primary site or must undergo re-resection of the primary site; a full lymphadenectomy meeting the criteria outlined is required for all node-positive patients including those with positive sentinel nodes; patients with recurrent disease who have had a prior complete lymphadenectomy fulfill this requirement as long as all recurrent disease has been resected; for all patients, all disease must have been resected with negative pathological margins and no clinical, radiologic, or pathological evidence of any incompletely resected melanoma; patients must be registered within 98 days of the last surgery performed to render the patient free of disease
Patients must have available and be willing to submit a minimum of five unstained slides from primary, lymph node, or metastatic site to determine PD-L1 expression; the tumor tissue must be adequate for PD-L1 testing (defined as >= 100 tumor cells as confirmed by the treating institution's local pathologist); this must be documented by having a pathologist sign the S1404 Local Pathology Review form prior to step 1 registration; the specimens may come from an archived block but must be submitted within 20 days from cutting the slides
Patients must be offered the opportunity to participate in specimen banking as outlined
Patients must be willing to have blood draws for PK/ADA analysis as outlined, should the patient be randomized to the MK-3475 arm
Patients may have received prior radiation therapy, including after the surgical resection; all adverse events associated with prior surgery and radiation therapy must have resolved to =< grade 1 prior to registration
Patients must not have received neoadjuvant treatment for their melanoma; patients must not have had prior immunotherapy including, but not limited to ipilimumab, interferon alfa-2b, high dose IL-2, pegylated (PEG)-IFN, anti-PD-1, anti-PD-L1 intra-tumoral, or vaccine therapies; patients must not be planning to receive any of the prohibited therapies during the screening or treatment phases of the study
Patients must not be planning to receive concomitant other biologic therapy, radiation therapy, hormonal therapy, other chemotherapy, surgery or other therapy after step 2 registration
All patients must have disease-free status documented by a complete physical examination and imaging studies within 42 days prior to registration; imaging studies must include a total body positron emission tomography (PET)-computed tomography (CT) scan that is of diagnostic quality (with or without brain) or a CT of the chest, abdomen and pelvis; for patients with melanoma arising from the head and neck, dedicated neck imaging (CT with IV contrast or PET-CT through the region) is required; if the patient has had unknown primary with disease in the axilla, neck imaging is required to assure region is clear of cancer; CT imaging should be done with intravenous contrast if there are no contraindications for it; any other clinically-indicated imaging studies if performed (e.g. bone scan) must show no evidence of disease
All patients must have a CT or magnetic resonance imaging (MRI) of the brain within 90 days prior to registration; the brain CT or MRI should be performed with intravenous contrast (unless contraindicated)
Absolute neutrophil count (ANC) >= 1,500 microliter (mcL) (within 42 days prior to registration)
Platelets >= 100,000 mcL (within 42 days prior to registration)
Hemoglobin >= 10 g/dL (within 42 days prior to registration)
Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (except Gilbert's syndrome, who must have a total bilirubin < 3.0 mg/dL) (within 42 days prior to registration)
Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2 x IULN (within 42 days prior to registration)
Alkaline phosphatase =< 2 x IULN (within 42 days prior to registration)
Serum creatinine =< IULN OR measured or calculated creatinine clearance >= 60 mL/min (within 42 days prior to registration)
Patients must have lactate dehydrogenase (LDH) performed within 42 days prior to registration
Patients must have Zubrod performance status =< 1
Patients must have a baseline electrocardiogram (ECG) performed within 42 days of registration that is normal or considered not clinically significant by the site investigator
Patients must not have a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
Patients must not have an active infection requiring systemic therapy
Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
Patients must not have received live vaccines within 42 days prior to registration; examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine; seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
Patients known to be human immunodeficiency virus (HIV) positive are eligible if they meet the following criteria within 30 days prior to registration: stable and adequate cluster of differentiation 4 (CD4) counts (>= 350 mm^3), and serum HIV viral load of < 25,000 IU/ml; patients may be on or off anti-viral therapy so long as they meet the CD4 count criteria
Patients must not have known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection prior to registration
Patients must not have a history or current evidence of any condition, therapy or laboratory abnormality that might confound the trial results, interfere with the patient's participation for the full duration of the trial, or indicate that participation in the trial is not in the patient's best interests, in the opinion of the treating investigator
No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, lobular carcinoma of the breast in situ, atypical melanocytic hyperplasia or melanoma in situ, adequately treated stage I or II cancer (including multiple primary melanomas) from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years
Women of childbearing potential must have a negative urine or serum pregnancy test within 28 days prior to registration; women/men of reproductive potential must have agreed to use an effective contraceptive method for the course of the study through 120 days after the last dose of study medication; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures, he/she is responsible for beginning contraceptive measures; patients must not be pregnant or nursing due to unknown teratogenic side effects
Patients who are able to complete questionnaires in English, Spanish or French must participate in the quality of life assessments; (those patients who cannot complete the quality of life questionnaires in English, Spanish or French can be registered to S1404 without contributing to the quality of life studies)
Patients must be informed of the investigational nature of this study and must sign and give written informed consent for this protocol in accordance with institutional and federal guidelines
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
STEP 2 REGISTRATION (RANDOMIZATION CRITERIA):
Patients must not be registered until receiving confirmation from the Southwest Oncology Group (SWOG) Statistical Center that the patient's tissue specimen was adequate for PD-L1 testing; patients must be registered within 7 working days of receiving the e-mail notification
Women of childbearing potential must plan to have a urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a negative serum pregnancy test will be required
No tests or exams are required to be repeated for step 2 registration (randomization); however, patients who are known to have a change in eligibility status after step 1 registration are not eligible for step 2 registration; for example, ANC is not required to be repeated between step 1 and step 2 registration, but the most recent ANC performed before step 2 registration is required to be >= 1,500 mcL

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: Double

Number of Arms

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I (high-dose recombinant interferon alfa-2B, ipilimumab) INDUCTION THERAPY: Patients receive high-dose recombinant interferon alfa-2B intravenously (IV) over 20 minutes on days 1-5. Treatment repeats weekly for 4 weeks in the absence of disease progression or unacceptable toxicity. Or patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 3 weeks for a total of 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive high-dose recombinant interferon alfa-2B subcutaneously (SC) on days 1, 3, and 5. Treatment repeats every 6 weeks for up to 48 weeks in the absence of disease progression or unacceptable toxicity. Or patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for 3 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, PET scan, MRI and blood sample collection throughout the study.	Other: Quality-of-Life Assessment Ancillary studies Other Names: Quality of Life Assessment Procedure: Magnetic Resonance Imaging Undergo MRI Other Names: MRI Magnetic Resonance Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI Scan NMR Imaging NMRI Nuclear Magnetic Resonance Imaging Magnetic Resonance Imaging (MRI) sMRI Magnetic resonance imaging (procedure) MRIs Structural MRI Biological: Ipilimumab Given IV Other Names: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody BMS-734016 Ipilimumab Biosimilar CS1002 MDX-010 MDX-CTLA4 Yervoy MDX010 BMS734016 BMS 734016 MDX 010 Procedure: Biospecimen Collection Undergo blood sample collection Other Names: Biological Sample Collection Biospecimen Collected Specimen Collection Procedure: Positron Emission Tomography Undergo PET scan Other Names: Medical Imaging, Positron Emission Tomography PET PET Scan Positron Emission Tomography Scan Positron-Emission Tomography PT Positron emission tomography (procedure) Procedure: Computed Tomography Undergo CT scan Other Names: CT CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized Tomography CT Scan tomography Computerized axial tomography (procedure) Computerized Tomography (CT) scan Diagnostic CAT Scan Diagnostic CAT Scan Service Type Biological: Recombinant Interferon Alfa-2b Given IV and SC Other Names: Alfatronol Glucoferon Heberon Alfa IFN alpha-2B Interferon alfa 2b Interferon Alfa-2B Interferon Alpha-2b Intron A Sch 30500 Urifron Viraferon Bioferon Bioferon (TM)
Experimental: Arm II (pembrolizumab) Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, PET scan, MRI and blood sample collection throughout the study.	Other: Quality-of-Life Assessment Ancillary studies Other Names: Quality of Life Assessment Procedure: Magnetic Resonance Imaging Undergo MRI Other Names: MRI Magnetic Resonance Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI Scan NMR Imaging NMRI Nuclear Magnetic Resonance Imaging Magnetic Resonance Imaging (MRI) sMRI Magnetic resonance imaging (procedure) MRIs Structural MRI Biological: Pembrolizumab Given IV Other Names: Keytruda MK-3475 Lambrolizumab SCH 900475 MK3475 SCH-900475 BCD-201 Pembrolizumab Biosimilar BCD-201 Pembrolizumab Biosimilar QL2107 QL2107 GME 751 GME751 Pembrolizumab Biosimilar GME751 MK 3475 SCH900475 Pembrolizumab Biosimilar RPH-075 RPH 075 RPH-075 RPH075 Pembrolizumab Biosimilar SB27 SB 27 SB-27 SB27 Procedure: Biospecimen Collection Undergo blood sample collection Other Names: Biological Sample Collection Biospecimen Collected Specimen Collection Procedure: Positron Emission Tomography Undergo PET scan Other Names: Medical Imaging, Positron Emission Tomography PET PET Scan Positron Emission Tomography Scan Positron-Emission Tomography PT Positron emission tomography (procedure)

Participant Group / Arm

Intervention / Treatment

Active Comparator: Arm I (high-dose recombinant interferon alfa-2B, ipilimumab)

Patients undergo CT scan, PET scan, MRI and blood sample collection throughout the study.

Other: Quality-of-Life Assessment

Ancillary studies

Other Names:

Quality of Life Assessment

Procedure: Magnetic Resonance Imaging

Undergo MRI

Other Names:

MRI
Magnetic Resonance
Magnetic Resonance Imaging Scan
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
MR
MR Imaging
MRI Scan
NMR Imaging
NMRI
Nuclear Magnetic Resonance Imaging
Magnetic Resonance Imaging (MRI)
sMRI
Magnetic resonance imaging (procedure)
MRIs
Structural MRI

Biological: Ipilimumab

Given IV

Other Names:

Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
BMS-734016
Ipilimumab Biosimilar CS1002
MDX-010
MDX-CTLA4
Yervoy
MDX010
BMS734016
BMS 734016
MDX 010

Procedure: Biospecimen Collection

Undergo blood sample collection

Other Names:

Biological Sample Collection
Biospecimen Collected
Specimen Collection

Procedure: Positron Emission Tomography

Undergo PET scan

Other Names:

Medical Imaging, Positron Emission Tomography
PET
PET Scan
Positron Emission Tomography Scan
Positron-Emission Tomography
PT
Positron emission tomography (procedure)

Procedure: Computed Tomography

Undergo CT scan

Other Names:

CT
CAT
CAT Scan
Computed Axial Tomography
Computerized Axial Tomography
Computerized Tomography
CT Scan
tomography
Computerized axial tomography (procedure)
Computerized Tomography (CT) scan
Diagnostic CAT Scan
Diagnostic CAT Scan Service Type

Biological: Recombinant Interferon Alfa-2b

Given IV and SC

Other Names:

Alfatronol
Glucoferon
Heberon Alfa
IFN alpha-2B
Interferon alfa 2b
Interferon Alfa-2B
Interferon Alpha-2b
Intron A
Sch 30500
Urifron
Viraferon
Bioferon
Bioferon (TM)

Experimental: Arm II (pembrolizumab)

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, PET scan, MRI and blood sample collection throughout the study.

Other: Quality-of-Life Assessment

Ancillary studies

Other Names:

Quality of Life Assessment

Procedure: Magnetic Resonance Imaging

Undergo MRI

Other Names:

MRI
Magnetic Resonance
Magnetic Resonance Imaging Scan
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
MR
MR Imaging
MRI Scan
NMR Imaging
NMRI
Nuclear Magnetic Resonance Imaging
Magnetic Resonance Imaging (MRI)
sMRI
Magnetic resonance imaging (procedure)
MRIs
Structural MRI

Biological: Pembrolizumab

Given IV

Other Names:

Keytruda
MK-3475
Lambrolizumab
SCH 900475
MK3475
SCH-900475
BCD-201
Pembrolizumab Biosimilar BCD-201
Pembrolizumab Biosimilar QL2107
QL2107
GME 751
GME751
Pembrolizumab Biosimilar GME751
MK 3475
SCH900475
Pembrolizumab Biosimilar RPH-075
RPH 075
RPH-075
RPH075
Pembrolizumab Biosimilar SB27
SB 27
SB-27
SB27

Procedure: Biospecimen Collection

Undergo blood sample collection

Other Names:

Biological Sample Collection
Biospecimen Collected
Specimen Collection

Procedure: Positron Emission Tomography

Undergo PET scan

Other Names:

Medical Imaging, Positron Emission Tomography
PET
PET Scan
Positron Emission Tomography Scan
Positron-Emission Tomography
PT
Positron emission tomography (procedure)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) Time Frame: 5 years after last randomization	Time from date of randomization to date of death due to any cause. Patients known to be alive are censored at date of last contact. The results were presented as 5-year OS estimate.	5 years after last randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse-free Survival (RFS) Time Frame: 5 years after last randomization	Time from date of randomization to date of first documentation of relapse or death due to any cause. Patients last known to be alive and relapse-free are censored at date of last contact.	5 years after last randomization
Overall Survival (OS) in Participants Who Are PD-L1 Positive Time Frame: 94 months; from study start November 10, 2015 to September 15, 2023	Time from date of randomization to date of death due to any cause. Patients known to be alive are censored at date of last contact.	94 months; from study start November 10, 2015 to September 15, 2023
Relapse-free Survival (RFS) in Participants Who Are PD-L1 Positive Time Frame: 5 years after last randomization	Time from date of randomization to date of first documentation of relapse or death due to any cause. Patients last known to be alive and relapse-free are censored at date of last contact.	5 years after last randomization
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Time Frame: Randomized patients will be followed until death or 94 months (from study start November 10, 2015 to September 15, 2023), whichever occurs first.	Only adverse events that are possibly, probably or definitely related to study drug are reported. CTCAE Version 5.0 was used for all AE reporting.	Randomized patients will be followed until death or 94 months (from study start November 10, 2015 to September 15, 2023), whichever occurs first.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

Principal Investigator: Sapna Patel, SWOG Cancer Research Network

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Unger JM, Darke A, Othus M, Truong TG, Khushalani N, Kendra K, Lewis KD, Faller B, Funchain P, Buchbinder EI, Tarhini AA, Kirkwood JM, Sharon E, Sondak V, Guild SR, Grossmann K, Ribas A, Patel SP. Effectiveness of Adjuvant Pembrolizumab vs High-Dose Interferon or Ipilimumab for Quality-of-Life Outcomes in Patients With Resected Melanoma: A Secondary Analysis of the SWOG S1404 Randomized Clinical Trial. JAMA Oncol. 2023 Feb 1;9(2):251-260. doi: 10.1001/jamaoncol.2022.5486.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 10, 2015

Primary Completion (Actual)

September 15, 2023

Study Completion (Estimated)

January 23, 2027

Study Registration Dates

First Submitted

July 22, 2015

First Submitted That Met QC Criteria

July 22, 2015

First Posted (Estimated)

July 23, 2015

Study Record Updates

Last Update Posted (Actual)

May 4, 2026

Last Update Submitted That Met QC Criteria

May 1, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

NCI-2014-02676 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
U10CA180888 (U.S. NIH Grant/Contract)
S1404 (Other Identifier: CTEP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Study Overview

Status

Conditions

Intervention / Treatment

Detailed Description

Study Type

Enrollment (Actual)

Phase

Contacts and Locations

Study Locations

Participation Criteria

Eligibility Criteria

Ages Eligible for Study

Accepts Healthy Volunteers

Description

Study Plan

How is the study designed?

Design Details

Number of Arms

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Secondary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Collaborators and Investigators

Sponsor

Investigators

Publications and helpful links

General Publications

Study record dates

Study Major Dates

Study Start (Actual)

Primary Completion (Actual)

Study Completion (Estimated)

Study Registration Dates

First Submitted

First Submitted That Met QC Criteria

First Posted (Estimated)

Study Record Updates

Last Update Posted (Actual)

Last Update Submitted That Met QC Criteria

Last Verified

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Clinical Trials on Metastatic Cutaneous Melanoma

Clinical Trials on Quality-of-Life Assessment

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Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Slovenia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations