Nivolumab in Treating Patients With Localized Kidney Cancer Undergoing Nephrectomy

October 6, 2023 updated by: National Cancer Institute (NCI)

A Phase 3 RandOmized Study Comparing PERioperative Nivolumab vs. Observation in Patients With Renal Cell Carcinoma Undergoing Nephrectomy (PROSPER RCC)

This phase III trial compares nephrectomy (surgery to remove a kidney or part of a kidney) with nivolumab to the usual approach of nephrectomy followed by standard post-operative follow-up and monitoring, in treating patients with kidney cancer that is limited to a certain part of the body (localized). Nivolumab is a drug that may help stimulate the immune system to attack any cancer cells that may remain after surgery. The addition of nivolumab to the usual surgery could prevent the cancer from returning. It is not yet known whether nivolumab and nephrectomy is more effective than nephrectomy alone in treating patients with kidney cancer.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To compare recurrence-free survival (RFS) between patients with renal cell carcinoma randomly assigned to perioperative nivolumab in conjunction with radical or partial nephrectomy with patients randomized to surgery alone.

SECONDARY OBJECTIVES:

I. To evaluate for differences in recurrence-free survival associated with perioperative nivolumab compared to surgery alone among the subset of patients with clear cell histology.

II. To compare the overall survival between the two arms. III. To describe the safety and tolerability of perioperative nivolumab.

CORRELATIVE OBJECTIVES:

I. To correlate the primary tumor's expression of PD-L1 with outcome. II. To correlate the expression of PD-L1 on tumor tissue at nephrectomy and recurrence with outcome.

III. To archive images for potential central confirmation of recurrence and for future correlative work with American College of Radiology Imaging Network (ACRIN), including markers predicting outcome or response.

IV. To prospectively collect tumor and biologic specimens (e.g., serum, peripheral blood mononuclear cells [PBMCs]) for future correlative studies.

V. To characterize the pharmacokinetics of nivolumab and explore exposure response relationships with respect to safety and efficacy.

VI. To characterize the immunogenicity of nivolumab.

QUALITY OF LIFE OBJECTIVE:

I. To evaluate differences in change from baseline in patient-reported symptoms and toxicities among patients randomized to treatment with nivolumab compared to surgery alone.

OTHER EXPLORATORY OBJECTIVES:

I. To explore descriptively the efficacy of treatment with nivolumab in patients with non-clear cell (including unclassified) histologies.

II. To characterize the effects of nivolumab on bone metabolism and bone density.

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

ARM I: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 14 days for 2 cycles. Patients then undergo partial or radical nephrectomy 7-28 days later. Patient then receive nivolumab over 30 IV on day 1. Treatment repeats every 14 days for 6 cycles, and then every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

Patients enrolled after Amendment 4 receive nivolumab IV over 30 minutes on day 1. Patients then undergo partial or radical nephrectomy 7-28 days later. Patients then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 9 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo partial or radical nephrectomy within 8 weeks after registration followed by observation.

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

Study Type

Interventional

Enrollment (Actual)

785

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
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Centre
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 0V9
        • CancerCare Manitoba
    • New Brunswick
      • Moncton, New Brunswick, Canada, E1C 6Z8
        • The Moncton Hospital
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 2Y9
        • QEII Health Sciences Centre/Nova Scotia Health Authority
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Juravinski Cancer Centre at Hamilton Health Sciences
      • Hamilton, Ontario, Canada, L8N 4A6
        • Saint Joseph's Healthcare Charlton Campus
      • Kingston, Ontario, Canada, K7L 2V7
        • Kingston Health Sciences Centre
      • London, Ontario, Canada, N6A 4L6
        • London Regional Cancer Program
      • Saint Catharines, Ontario, Canada, L2S 0A9
        • Niagara Health System-Saint Catharines General
      • 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
      • Montreal, Quebec, Canada, H2X 3E4
        • CHUM - Centre Hospitalier de l'Universite de Montreal
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
  • Israel
      • Haifa, Israel, 31096
        • Rambam Medical Center
      • Jerusalem, Israel, 91031
        • Shaare Zedek Medical Center
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham Cancer Center
      • Birmingham, Alabama, United States, 35233
        • Veterans Administration Medical Center - Birmingham
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • Banner Md Anderson Cancer Center
      • Phoenix, Arizona, United States, 85004
        • Cancer Center at Saint Joseph's
      • Tucson, Arizona, United States, 85719
        • Banner University Medical Center - Tucson
      • Tucson, Arizona, United States, 85719
        • University of Arizona Cancer Center-North Campus
    • California
      • Anaheim, California, United States, 92806
        • Kaiser Permanente-Anaheim
      • Auburn, California, United States, 95602
        • Sutter Auburn Faith Hospital
      • Bakersfield, California, United States, 93301
        • AIS Cancer Center at San Joaquin Community Hospital
      • Baldwin Park, California, United States, 91706
        • Kaiser Permanente-Baldwin Park
      • Bellflower, California, United States, 90706
        • Kaiser Permanente-Bellflower
      • Berkeley, California, United States, 94704
        • Alta Bates Summit Medical Center-Herrick Campus
      • Burlingame, California, United States, 94010
        • Mills-Peninsula Medical Center
      • Clovis, California, United States, 93611
        • Community Cancer Institute
      • Duarte, California, United States, 91010
        • City of Hope Comprehensive Cancer Center
      • Fontana, California, United States, 92335
        • Kaiser Permanente-Fontana
      • Harbor City, California, United States, 90710
        • Kaiser Permanente - Harbor City
      • 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, 90095
        • UCLA / Jonsson Comprehensive Cancer Center
      • Los Angeles, California, United States, 90027
        • Kaiser Permanente Los Angeles Medical Center
      • Los Angeles, California, United States, 90048
        • Cedars Sinai Medical Center
      • Los Angeles, California, United States, 90034
        • Kaiser Permanente West Los Angeles
      • Marysville, California, United States, 95901
        • Fremont - Rideout Cancer Center
      • Mountain View, California, United States, 94040
        • Palo Alto Medical Foundation-Camino Division
      • Newport Beach, California, United States, 92663
        • USC Norris Oncology/Hematology-Newport Beach
      • Oakland, California, United States, 94611
        • Kaiser Permanente-Oakland
      • Ontario, California, United States, 91761
        • Kaiser Permanente-Ontario
      • Orange, California, United States, 92868
        • UC Irvine Health/Chao Family Comprehensive Cancer Center
      • Palo Alto, California, United States, 94304
        • VA Palo Alto Health Care System
      • 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
      • Rancho Mirage, California, United States, 92270
        • Eisenhower Medical Center
      • 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, 95814
        • Kaiser Permanente Downtown Commons
      • Sacramento, California, United States, 95825
        • Kaiser Permanente - Sacramento
      • San Diego, California, United States, 92120
        • Kaiser Permanente-San Diego Zion
      • 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 Luis Obispo, California, United States, 93401
        • Pacific Central Coast Health Center-San Luis Obispo
      • San Marcos, California, United States, 92078
        • Kaiser Permanente-San Marcos
      • Santa Clara, California, United States, 95051
        • Kaiser Permanente Medical Center - Santa Clara
      • Santa Cruz, California, United States, 95065
        • Palo Alto Medical Foundation-Santa Cruz
      • South San Francisco, California, United States, 94080
        • Kaiser Permanente-South San Francisco
      • Sunnyvale, California, United States, 94086
        • Palo Alto Medical Foundation-Sunnyvale
      • Truckee, California, United States, 96161
        • Gene Upshaw Memorial Tahoe Forest Cancer Center
      • Vallejo, California, United States, 94589
        • Kaiser Permanente-Vallejo
      • Vallejo, California, United States, 94589
        • Sutter Solano Medical Center/Cancer Center
      • Walnut Creek, California, United States, 94596
        • Kaiser Permanente-Walnut Creek
      • Whittier, California, United States, 90602
        • Presbyterian Intercommunity Hospital
      • 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, 80909
        • UCHealth Memorial Hospital Central
      • Colorado Springs, Colorado, United States, 80920
        • Memorial Hospital North
      • Fort Collins, Colorado, United States, 80524
        • Poudre Valley Hospital
      • Fort Collins, Colorado, United States, 80528
        • Cancer Care and Hematology-Fort Collins
      • Greeley, Colorado, United States, 80631
        • UCHealth Greeley Hospital
      • Loveland, Colorado, United States, 80538
        • Medical Center of the Rockies
    • Connecticut
      • Hartford, Connecticut, United States, 06102
        • Hartford Hospital
      • Meriden, Connecticut, United States, 06451
        • Midstate Medical Center
      • New Britain, Connecticut, United States, 06050
        • The Hospital of Central Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale University
      • Norwich, Connecticut, United States, 06360
        • Eastern Connecticut Hematology and Oncology Associates
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • MedStar Washington Hospital Center
      • Washington, District of Columbia, United States, 20016
        • Sibley Memorial Hospital
      • Washington, District of Columbia, United States, 20037
        • George Washington University Medical Center
    • Florida
      • Coral Gables, Florida, United States, 33146
        • UM Sylvester Comprehensive Cancer Center at Coral Gables
      • Deerfield Beach, Florida, United States, 33442
        • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
      • Fort Lauderdale, Florida, United States, 33308
        • Holy Cross Hospital
      • Gainesville, Florida, United States, 32610
        • University of Florida Health Science Center - Gainesville
      • Jacksonville, Florida, United States, 32207
        • Baptist MD Anderson Cancer Center
      • Lakeland, Florida, United States, 33805
        • Lakeland Regional Health Hollis Cancer Center
      • Lakeland, Florida, United States, 33805
        • The Watson Clinic
      • Miami, Florida, United States, 33136
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
      • Miami, Florida, United States, 33176
        • Miami Cancer Institute
      • Miami, Florida, United States, 33176
        • UM Sylvester Comprehensive Cancer Center at Kendall
      • Plantation, Florida, United States, 33324
        • UM Sylvester Comprehensive Cancer Center at Plantation
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital/Winship Cancer Institute
      • Decatur, Georgia, United States, 30033
        • Atlanta VA Medical Center
    • Hawaii
      • 'Aiea, Hawaii, United States, 96701
        • Pali Momi Medical Center
      • 'Aiea, Hawaii, United States, 96701
        • Hawaii Cancer Care - Westridge
      • 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, 96817
        • Queen's Cancer Center - Kuakini
    • Idaho
      • 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, 83686
        • Saint Luke's Cancer Institute - Nampa
      • Post Falls, Idaho, United States, 83854
        • Kootenai Clinic Cancer Services - Post Falls
      • Sandpoint, Idaho, United States, 83864
        • Kootenai Cancer Clinic
      • Twin Falls, Idaho, United States, 83301
        • Saint Luke's Cancer Institute - Twin Falls
    • Illinois
      • Bloomington, Illinois, United States, 61704
        • Illinois CancerCare-Bloomington
      • Canton, Illinois, United States, 61520
        • Illinois CancerCare-Canton
      • Carthage, Illinois, United States, 62321
        • Illinois CancerCare-Carthage
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60637
        • University of Chicago Comprehensive Cancer Center
      • Chicago, Illinois, United States, 60612
        • University of Illinois
      • Danville, Illinois, United States, 61832
        • Carle at The Riverfront
      • 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
      • Galesburg, Illinois, United States, 61401
        • Illinois CancerCare-Galesburg
      • Geneva, Illinois, United States, 60134
        • Northwestern Medicine Cancer Center Delnor
      • Hines, Illinois, United States, 60141
        • Edward Hines Jr VA 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
      • O'Fallon, Illinois, United States, 62269
        • Cancer Care Center of O'Fallon
      • 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
      • Springfield, Illinois, United States, 62702
        • Southern Illinois University School of Medicine
      • Springfield, Illinois, United States, 62702
        • Springfield Clinic
      • 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
    • Indiana
      • Fort Wayne, Indiana, United States, 46845
        • Parkview Regional Medical Center
      • 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, 46202
        • Sidney and Lois Eskenazi Hospital
      • Michigan City, Indiana, United States, 46360
        • Woodland Cancer Care Center
      • Mooresville, Indiana, United States, 46158
        • Franciscan Health Mooresville
      • Richmond, Indiana, United States, 47374
        • Reid Health
      • South Bend, Indiana, United States, 46601
        • Memorial Hospital of South Bend
    • 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
      • Clive, Iowa, United States, 50325
        • Mercy Cancer Center-West Lakes
      • Clive, Iowa, United States, 50325
        • Medical Oncology and Hematology Associates-West Des Moines
      • Des Moines, Iowa, United States, 50314
        • Mercy Medical Center - Des Moines
      • Des Moines, Iowa, United States, 50314
        • Mission Cancer and Blood - Laurel
      • Fort Dodge, Iowa, United States, 50501
        • McFarland Clinic - Trinity 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
      • Hays, Kansas, United States, 67601
        • HaysMed University of Kansas Health System
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Cancer Center
      • Lawrence, Kansas, United States, 66044
        • Lawrence Memorial Hospital
      • Olathe, Kansas, United States, 66061
        • Olathe Health Cancer Center
      • Overland Park, Kansas, United States, 66210
        • University of Kansas Cancer Center-Overland Park
      • Pittsburg, Kansas, United States, 66762
        • Ascension Via Christi - Pittsburg
      • Salina, Kansas, United States, 67401
        • Salina Regional Health Center
      • Topeka, Kansas, United States, 66606
        • University of Kansas Health System Saint Francis Campus
      • Topeka, Kansas, United States, 66606
        • Cotton O'Neil Cancer Center / Stormont Vail Health
      • Westwood, Kansas, United States, 66205
        • University of Kansas Hospital-Westwood Cancer Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky/Markey 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, 70809
        • Our Lady of the Lake Physicians Group - Medical Oncology
      • Covington, Louisiana, United States, 70433
        • Northshore Oncology Associates-Covington
      • Houma, Louisiana, United States, 70360
        • Oncology Center of The South Incorporated
      • Metairie, Louisiana, United States, 70006
        • East Jefferson General Hospital
      • Metairie, Louisiana, United States, 70006
        • LSU Healthcare Network / Metairie Multi-Specialty Clinic
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Medical Center Jefferson
      • New Orleans, Louisiana, United States, 70112
        • Tulane University Health Sciences Center
      • New Orleans, Louisiana, United States, 70112
        • University Medical Center New Orleans
      • New Orleans, Louisiana, United States, 70112
        • Louisiana State University Health Science 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
      • Belfast, Maine, United States, 04915
        • Waldo County General Hospital
      • Biddeford, Maine, United States, 04005
        • MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford
      • Brewer, Maine, United States, 04412
        • Lafayette Family Cancer Center-EMMC
      • Rockport, Maine, United States, 04856
        • Penobscot Bay Medical Center
      • Sanford, Maine, United States, 04073
        • MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford
      • South Portland, Maine, United States, 04106
        • Maine Medical Partners - South Portland
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University/Sidney Kimmel Cancer Center
      • Baltimore, Maryland, United States, 21204
        • Greater Baltimore Medical Center
    • 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, 02115
        • Brigham and Women's Hospital
      • 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
      • Fitchburg, Massachusetts, United States, 01420
        • Simonds-Sinon Regional Cancer Center
      • Winchester, Massachusetts, United States, 01890
        • Winchester Hospital
      • Worcester, Massachusetts, United States, 01655
        • UMass Memorial Medical Center - University Campus
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Comprehensive Cancer Center
      • Ann Arbor, Michigan, United States, 48106
        • Saint Joseph Mercy Hospital
      • Brighton, Michigan, United States, 48114
        • Saint Joseph Mercy Brighton
      • Canton, Michigan, United States, 48188
        • Saint Joseph Mercy Canton
      • Chelsea, Michigan, United States, 48118
        • Saint Joseph Mercy Chelsea
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
      • Detroit, Michigan, United States, 48201
        • Wayne State University/Karmanos Cancer Institute
      • Farmington Hills, Michigan, United States, 48334
        • Weisberg Cancer Treatment Center
      • Grand Rapids, Michigan, United States, 49503
        • Spectrum Health at Butterworth Campus
      • Lansing, Michigan, United States, 48912
        • Sparrow Hospital
      • Novi, Michigan, United States, 48374
        • Ascension Providence Hospitals - Novi
      • Royal Oak, Michigan, United States, 48073
        • William Beaumont Hospital-Royal Oak
      • Southfield, Michigan, United States, 48075
        • Ascension Providence Hospitals - Southfield
      • Troy, Michigan, United States, 48085
        • William Beaumont Hospital - Troy
    • Minnesota
      • Minneapolis, Minnesota, United States, 55407
        • Abbott-Northwestern Hospital
      • Minneapolis, Minnesota, United States, 55417
        • Minneapolis VA Medical Center
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester
      • Saint Cloud, Minnesota, United States, 56303
        • Coborn Cancer Center at Saint Cloud Hospital
    • Mississippi
      • Gulfport, Mississippi, United States, 39502
        • Gulfport Memorial Hospital
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • Cape Girardeau, Missouri, United States, 63703
        • Saint Francis Medical Center
      • Chesterfield, Missouri, United States, 63017
        • Saint Luke's Hospital
      • Columbia, Missouri, United States, 65212
        • MU Health - University Hospital/Ellis Fischel Cancer Center
      • Creve Coeur, Missouri, United States, 63141
        • Siteman Cancer Center at West County Hospital
      • Kansas City, Missouri, United States, 64154
        • University of Kansas Cancer Center - North
      • Kansas City, Missouri, United States, 64108
        • Truman Medical Centers
      • Lee's Summit, Missouri, United States, 64064
        • University of Kansas Cancer Center - Lee's Summit
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • Saint Louis, Missouri, United States, 63131
        • Missouri Baptist Medical Center
      • Saint Louis, Missouri, United States, 63141
        • Mercy Hospital Saint Louis
      • Saint Peters, Missouri, United States, 63376
        • Siteman Cancer Center at Saint Peters Hospital
    • Montana
      • Bozeman, Montana, United States, 59715
        • Bozeman Deaconess Hospital
      • Great Falls, Montana, United States, 59405
        • Benefis Healthcare- Sletten Cancer Institute
    • Nebraska
      • Grand Island, Nebraska, United States, 68803
        • CHI Health Saint Francis
      • Omaha, Nebraska, United States, 68114
        • Nebraska Methodist Hospital
    • Nevada
      • Henderson, Nevada, United States, 89052
        • OptumCare Cancer Care at Seven Hills
      • Las Vegas, Nevada, United States, 89102
        • OptumCare Cancer Care at Charleston
      • Las Vegas, Nevada, United States, 89144
        • Comprehensive Cancer Centers of Nevada - Town Center
      • Las Vegas, Nevada, United States, 89148
        • OptumCare Cancer Care at Fort Apache
      • Las Vegas, Nevada, United States, 89169
        • Comprehensive Cancer Centers of Nevada - Central Valley
      • Las Vegas, Nevada, United States, 89169
        • University Cancer Center
      • Reno, Nevada, United States, 89502
        • Renown Regional Medical Center
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
    • New Jersey
      • Englewood, New Jersey, United States, 07631
        • Englewood Hospital and Medical Center
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers Cancer Institute of New Jersey
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
      • Somerville, New Jersey, United States, 08876
        • Robert Wood Johnson University Hospital Somerset
    • New York
      • Albany, New York, United States, 12208
        • Albany Medical Center
      • Bronx, New York, United States, 10461
        • Montefiore Medical Center-Einstein Campus
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center - Moses Campus
      • Bronx, New York, United States, 10461
        • Montefiore Medical Center-Weiler Hospital
      • Bronx, New York, United States, 10468
        • James J Peters VA Medical Center
      • Glens Falls, New York, United States, 12801
        • Glens Falls Hospital
      • Lake Success, New York, United States, 11042
        • Northwell Health/Center for Advanced Medicine
      • New Hyde Park, New York, United States, 11040
        • Long Island Jewish Medical Center
      • New York, New York, United States, 10065
        • NYP/Weill Cornell Medical Center
      • New York, New York, United States, 10016
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
      • Rochester, New York, United States, 14642
        • University of Rochester
      • Syracuse, New York, United States, 13210
        • State University of New York Upstate Medical University
      • White Plains, New York, United States, 10601
        • Dickstein Cancer Treatment Center
    • North Carolina
      • Cary, North Carolina, United States, 27518
        • Rex Hematology Oncology Associates-Cary
      • 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
      • Jacksonville, North Carolina, United States, 28546
        • Southeastern Medical Oncology Center-Jacksonville
      • Jacksonville, North Carolina, United States, 28546
        • Onslow Memorial Hospital
      • Kenansville, North Carolina, United States, 28349
        • Vidant Oncology-Kenansville
      • Kinston, North Carolina, United States, 28501
        • Vidant Oncology-Kinston
      • Raleigh, North Carolina, United States, 27607
        • UNC Rex Healthcare
      • Raleigh, North Carolina, United States, 27614
        • UNC Rex Cancer Center of Wakefield
      • Raleigh, North Carolina, United States, 27607
        • Rex Hematology Oncology Associates-Blue Ridge
      • Richlands, North Carolina, United States, 28574
        • Vidant Oncology-Richlands
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
      • Winston-Salem, North Carolina, United States, 27103
        • Novant Health Forsyth Medical Center
    • 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
    • Ohio
      • Akron, Ohio, United States, 44304
        • Summa Health System - Akron Campus
      • Beachwood, Ohio, United States, 44122
        • UHHS-Chagrin Highlands Medical Center
      • Centerville, Ohio, United States, 45459
        • Dayton Physicians LLC-Miami Valley South
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati Cancer Center-UC Medical Center
      • Cincinnati, Ohio, United States, 45220
        • Good Samaritan Hospital - Cincinnati
      • Cincinnati, Ohio, United States, 45242
        • Bethesda North Hospital
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University
      • Cleveland, Ohio, United States, 44109
        • MetroHealth Medical Center
      • Franklin, Ohio, United States, 45005
        • Dayton Physicians LLC-Atrium
      • Kettering, Ohio, United States, 45429
        • Kettering Medical Center
      • Middleburg Heights, Ohio, United States, 44130
        • UH Seidman Cancer Center at Southwest General Hospital
      • Toledo, Ohio, United States, 43623
        • Toledo Clinic Cancer Centers-Toledo
      • West Chester, Ohio, United States, 45069
        • University of Cincinnati Cancer Center-West Chester
      • Westlake, Ohio, United States, 44145
        • UH Seidman Cancer Center at Saint John Medical 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
      • Clackamas, Oregon, United States, 97015
        • Providence Cancer Institute Clackamas Clinic
      • Medford, Oregon, United States, 97504
        • Rogue Valley Medical Center
      • Newberg, Oregon, United States, 97132
        • Providence Newberg Medical Center
      • Oregon City, Oregon, United States, 97045
        • Providence Willamette Falls Medical Center
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
      • Portland, Oregon, United States, 97213
        • Providence Portland Medical Center
      • Portland, Oregon, United States, 97225
        • Providence Saint Vincent Medical Center
      • Portland, Oregon, United States, 97227
        • Kaiser Permanente Northwest
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Lehigh Valley Hospital-Cedar Crest
      • Bethlehem, Pennsylvania, United States, 18017
        • Lehigh Valley Hospital - Muhlenberg
      • Danville, Pennsylvania, United States, 17822
        • Geisinger Medical Center
      • Hershey, Pennsylvania, United States, 17033-0850
        • Penn State Milton S Hershey Medical Center
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania/Abramson Cancer Center
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University Hospital
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Cancer Institute (UPCI)
      • West Reading, Pennsylvania, United States, 19611
        • Reading Hospital
      • Williamsport, Pennsylvania, United States, 17701
        • UPMC Susquehanna
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital
      • Providence, Rhode Island, United States, 02906
        • Miriam Hospital
    • South Carolina
      • Boiling Springs, South Carolina, United States, 29316
        • Prisma Health Cancer Institute - Spartanburg
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
      • Charleston, South Carolina, United States, 29401
        • Ralph H Johnson VA Medical Center
      • Clinton, South Carolina, United States, 29325
        • Prisma Health Cancer Institute - Laurens
      • Easley, South Carolina, United States, 29640
        • Prisma Health Cancer Institute - Easley
      • Gaffney, South Carolina, United States, 29341
        • Gibbs Cancer Center-Gaffney
      • Greenville, South Carolina, United States, 29605
        • Prisma Health Cancer Institute - Faris
      • Greenville, South Carolina, United States, 29607
        • Saint Francis Cancer Center
      • Greenville, South Carolina, United States, 29615
        • Prisma Health Cancer Institute - Eastside
      • Greenville, South Carolina, United States, 29605
        • Prisma Health Cancer Institute - Butternut
      • Greenville, South Carolina, United States, 29601
        • Saint Francis Hospital
      • Greer, South Carolina, United States, 29650
        • Prisma Health Cancer Institute - Greer
      • Greer, South Carolina, United States, 29651
        • Gibbs Cancer Center-Pelham
      • Seneca, South Carolina, United States, 29672
        • Prisma Health Cancer Institute - Seneca
      • Spartanburg, South Carolina, United States, 29303
        • Spartanburg Medical Center
      • West Columbia, South Carolina, United States, 29169
        • Lexington Medical Center
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University/Ingram Cancer Center
      • Nashville, Tennessee, United States, 37208
        • Meharry Medical College
    • Texas
      • Dallas, Texas, United States, 75390
        • UT Southwestern/Simmons Cancer Center-Dallas
      • Fort Worth, Texas, United States, 76104
        • UT Southwestern/Simmons Cancer Center-Fort Worth
      • Galveston, Texas, United States, 77555-0565
        • University of Texas Medical Branch
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
      • Houston, Texas, United States, 77030
        • Ben Taub General Hospital
      • League City, Texas, United States, 77573
        • UTMB Cancer Center at Victory Lakes
      • Richardson, Texas, United States, 75080
        • UT Southwestern Clinical Center at Richardson/Plano
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Center at San Antonio
      • San Antonio, Texas, United States, 78229
        • Audie L Murphy VA Hospital
    • Utah
      • Farmington, Utah, United States, 84025
        • Farmington Health Center
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute/University of Utah
      • South Jordan, Utah, United States, 84009
        • South Jordan Health Center
    • Vermont
      • Berlin, 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
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Cancer Center
      • Martinsville, Virginia, United States, 24115
        • Sovah Health Martinsville
      • Mechanicsville, Virginia, United States, 23116
        • Bon Secours Memorial Regional Medical Center
      • Midlothian, Virginia, United States, 23114
        • Bon Secours Saint Francis Medical Center
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University/Massey Cancer Center
      • Richmond, Virginia, United States, 23226
        • Bon Secours Saint Mary's Hospital
    • Washington
      • Bremerton, Washington, United States, 98310
        • Harrison HealthPartners Hematology and Oncology-Bremerton
      • Kennewick, Washington, United States, 99336
        • Kadlec Clinic Hematology and Oncology
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center - Montlake
      • Seattle, Washington, United States, 98109
        • FHCC South Lake Union
    • Wisconsin
      • Antigo, Wisconsin, United States, 54409
        • Langlade Hospital and Cancer Center
      • Appleton, Wisconsin, United States, 54911
        • ThedaCare Regional Cancer Center
      • Brookfield, Wisconsin, United States, 53045
        • Ascension Southeast Wisconsin Hospital - Elmbrook Campus
      • Burlington, Wisconsin, United States, 53105
        • Aurora Cancer Care-Southern Lakes VLCC
      • Eau Claire, Wisconsin, United States, 54701
        • Marshfield Medical Center-EC Cancer Center
      • Fond Du Lac, Wisconsin, United States, 54937
        • Aurora Health Center-Fond du Lac
      • Franklin, Wisconsin, United States, 53132
        • Ascension Saint Francis - Reiman 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
      • Johnson Creek, Wisconsin, United States, 53038
        • UW Cancer Center Johnson Creek
      • Kenosha, Wisconsin, United States, 53142
        • Aurora Cancer Care-Kenosha South
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Carbone Cancer Center
      • Madison, Wisconsin, United States, 53705
        • William S Middleton VA Medical Center
      • Marinette, Wisconsin, United States, 54143
        • Aurora Bay Area Medical Group-Marinette
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Medical Center-Marshfield
      • Medford, Wisconsin, United States, 54451
        • Aspirus Medford 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
      • Minocqua, Wisconsin, United States, 54548
        • Marshfield Clinic-Minocqua Center
      • Mukwonago, Wisconsin, United States, 53149
        • ProHealth D N Greenwald Center
      • Oconomowoc, Wisconsin, United States, 53066
        • ProHealth Oconomowoc Memorial Hospital
      • 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
      • Sheboygan, Wisconsin, United States, 53081
        • Vince Lombardi Cancer Clinic-Sheboygan
      • Stevens Point, Wisconsin, United States, 54482
        • Marshfield Medical Center-River Region at Stevens Point
      • Summit, Wisconsin, United States, 53066
        • Aurora Medical Center in Summit
      • Two Rivers, Wisconsin, United States, 54241
        • Vince Lombardi Cancer Clinic-Two Rivers
      • Waukesha, Wisconsin, United States, 53188
        • UW Cancer Center at ProHealth Care
      • Waukesha, Wisconsin, United States, 53188
        • ProHealth Waukesha Memorial Hospital
      • 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
      • Wauwatosa, Wisconsin, United States, 53226
        • Ascension Medical Group Southeast Wisconsin - Mayfair Road
      • 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

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

No

Description

Inclusion Criteria:

  • ELIGIBILITY CRITERIA FOR RANDOMIZATION:
  • Patients must have a renal mass consistent with a clinical stage >= T2Nx renal cell carcinoma (RCC) or TanyN+ RCC for which radical or partial nephrectomy is planned

  • Patients must have no clinical or radiological evidence of distant metastases (M0) unless the presumed M1 disease is planned to be resected/definitively treated (e.g., thermal ablation, stereotactic radiation) at the same time or up to 12 weeks after the date of the initial procedure such that the patient is considered "no evidence of disease" (M1 NED)

    • Liver, bone, or brain metastases are not permitted
    • No more than 3 metastases are permitted, and all must be able to be removed or definitively treated within 12 weeks of the primary tumor resection

  • If histological confirmation of RCC has not been done within 12 months prior to randomization, patient must be willing to undergo a core biopsy for this purpose if randomized to Arm A

    • NOTE: This histologic confirmation can be a (1) standard of care diagnostic biopsy or (2) a research biopsy or a planned metastasectomy. Tissue must be obtained with results available prior to the neoadjuvant dose

      • Patients randomized to Arm A: core tumor biopsy must have demonstrated RCC of any histology, including sarcomatoid, unclassified, or "unknown histology" (if preoperative biopsy was uninformative) with exception below for non-diagnostic biopsies
      • If the biopsy performed following randomization clearly demonstrates a benign condition, oncocytoma or a different type of cancer that is not RCC, the patient is not eligible and must come off study
      • A non-diagnostic biopsy is considered a good faith effort and does not need to be repeated unless deemed clinically necessary by the treating investigator

  • Patient must not have any prior systemic or local anti-cancer therapy for the current RCC

    • Patient must not have undergone a partial nephrectomy for the current RCC
    • Patient must not have had a metastasectomy for the current RCC diagnosis unless performed to render patient NED (in addition to the planned nephrectomy) within 6 months prior to the current diagnosis
    • Patient must not have received current or past antineoplastic systemic therapies for RCC: i.e., chemotherapy, hormonal therapy, immunotherapy, or standard or investigational agents for treatment of RCC
    • Patient must not have received prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
  • Patient must be >= 18 years of age. Because no dosing or adverse event data are currently available on the use of nivolumab therapy in patients < 18 years of age, children are excluded from this study
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

  • Patient must not have a prior history of RCC that was treated with curative intent within the past 5 years

    • Patients with a prior RCC that was treated > 5 years before, are eligible if the current tumor is consistent with a new primary in the opinion of the treating investigator

    • Patients with bilateral synchronous RCCs are eligible if they can be resected or definitively treated at the same time or within a 12 week window from time of initial nephrectomy (partial or radical) or procedure and maintain adequate residual renal function; the patient is not eligible if both kidneys are to be completely removed and subsequent hemodialysis will be required

      • Permitted forms of local therapy for second tumor:

        • Partial or radical nephrectomy
        • If kidney tumor is =< 3 cm: thermal ablation (e.g., radiofrequency ablation, cryoablation or stereotactic radiosurgery)

  • Patients cannot have concurrent malignancies, with the following exceptions:

    • Adequately treated basal cell or squamous cell skin cancer

    • In situ cervical cancer

      • A history of superficial Ta urothelial cancer is permitted (as long as not currently undergoing treatment) whereas T1 or greater disease is excluded if < 3 years from diagnosis; concurrent persistent disease is not permitted
      • Adequately treated stage I or II cancer from which the patient is currently in complete remission
      • Any other cancer and stage from which the patient has been disease-free for at least 3 years prior to the time of randomization and as long as they are not receiving any current treatment (e.g. adjuvant or maintenance systemic or local therapy)
      • Concurrent low risk prostate cancer on active surveillance
  • Patient must not have active known or suspected autoimmune disease. The following autoimmune disorders are permitted: patients with vitiligo, type I diabetes mellitus, controlled/stable hypo or hyperthyroidism due to autoimmune or non-autoimmune conditions (hormone replacement is allowed), psoriasis not requiring systemic treatment, or other conditions not expected to recur

  • Patient must not have any ongoing condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications with the exceptions outlined below; patient must not have received any treatment with other immunosuppressive agents within 14 days prior to the first dose of study drug with the following exceptions:

    • Topical, ocular, intra-articular, intranasal, inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone or the equivalent are permitted in the absence of active autoimmune disease
    • A brief (less than 3 weeks) course of corticosteroids (any amount) for prophylaxis (for example: contrast dye allergy) or for treatment of non-autoimmune conditions (for example: nausea, delayed-type hypersensitivity reaction caused by a contact allergen) is permitted
  • Patient must not have uncontrolled adrenal insufficiency

  • Patient must not have known evidence of chronic active liver disease or evidence of acute or chronic hepatitis B Virus (HBV) or hepatitis C (HCV); HBV and HCV testing must be completed within 8 weeks prior to randomization

    • NOTE: If the patient has been treated and cured, and the HCV ribonucleic acid (RNA) is undetectable, the patient is eligible for this study
  • Patient must not have any serious intercurrent illness, including ongoing or active infection requiring parenteral antibiotics
  • Patient must not have known evidence of human immunodeficiency virus (HIV) infection, since the effects of nivolumab on anti-retroviral therapy have not been studied; HIV testing is only required if past or current history is suspected
  • Patient must not have any known medical condition (e.g. a condition associated with uncontrolled diarrhea such as ulcerative colitis or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or interfere with the interpretation of safety results
  • Patient must not have had any major surgery within 28 days prior to randomization
  • Patient must not be currently enrolled in other clinical trials testing a therapeutic intervention
  • Patient must not have any history of severe hypersensitivity to a monoclonal antibody
  • Patient must have the ability to understand and the willingness to sign a written informed consent document
  • Patients must not be pregnant or breast-feeding, as the effects of nivolumab on the developing human fetus or in the nursing infant are unknown; all patients of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy; a patient of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception, as described in the informed consent form (ICF), or by abstaining from sexual intercourse for the duration of their participation in the study; patients of childbearing potential must use adequate methods to avoid pregnancy for 5 months after the last dose of nivolumab
  • White blood cells >= 2000/uL (within 8 weeks prior to randomization)
  • Absolute neutrophil count (ANC) >= 1,500/mm^3 (within 8 weeks prior to randomization)
  • Platelet count >= 100,000/mm^3 (within 8 weeks prior to randomization)
  • Hemoglobin >= 9.0 g/dL (within 8 weeks prior to randomization)
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) or calculated creatinine clearance (CrCl) >= 40mL/min (within 8 weeks prior to randomization)
  • Total bilirubin =< 1.5 x ULN (except subjects with Gilbert syndrome, who can have total bilirubin < 3.0 x ULN) (within 8 weeks prior to randomization)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN (within 8 weeks prior to randomization)

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: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I (nivolumab, nephrectomy)

Patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 14 days for 2 cycles. Patients then undergo partial or radical nephrectomy 7-28 days later. Patients then receive nivolumab over 30 IV on day 1. Treatment repeats every 14 days for 6 cycles, and then every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

Patients enrolled after Amendment 4 receive nivolumab IV over 30 minutes on day 1. Patients then undergo partial or radical nephrectomy 7-28 days later. Patient then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 9 cycles in the absence of disease progression or unacceptable toxicity.
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
  • CMAB819
  • Nivolumab Biosimilar CMAB819
  • ABP 206
  • Nivolumab Biosimilar ABP 206
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Procedure: Nephrectomy
Undergo nephrectomy
Active Comparator: Arm II (nephrectomy)
Patients undergo partial or radical nephrectomy within 8 weeks after registration followed by observation.
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Other: Patient Observation
Undergo observation
Other Names:
  • Observation
  • Active Surveillance
  • deferred therapy
  • expectant management
  • Watchful Waiting
Procedure: Nephrectomy
Undergo nephrectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free survival (EFS)
Time Frame: Time from randomization to disease recurrence or death from any cause, assessed up to 10 years
Will be assessed among all randomized patients using a stratified log rank test, with nominal one-sided type I error of 2.5%. The type I error will be adjusted for interim analyses.
Time from randomization to disease recurrence or death from any cause, assessed up to 10 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Time from randomization to death from any cause, assessed up to 10 years
Time from randomization to death from any cause, assessed up to 10 years
RFS among patients with clear cell cancer
Time Frame: Up to 10 years
The stratified logrank test will be used.
Up to 10 years
Incidence of toxicity
Time Frame: Up to 10 years
Graded per Common Criteria for Adverse Events (CTCAE) version (v)4.0. (Starting April 1, 2018, Cancer Therapy Evaluation Program Adverse Event Reporting System [CTEP-AERS] reporting will use CTCAE v5). Adverse events will be described separately for patients treated on each arm to evaluate safety and tolerability.
Up to 10 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary tumor's expression of PD-L1
Time Frame: Baseline to up to 10 years
The percentage of cells exhibiting cell-surface staining for PD-L1 will be scored. PD-L1 positivity will be defined per specimen by a 5% expression threshold. Additional analyses will assess the 1% and 10% threshold levels. Information with respect to the relative abundance and location (peritumoral/intratumoral) of immune cell (macrophage and lymphocyte) PD-L1 staining will be captured. The expression-by-treatment interaction will be tested using a proportional hazards model. McNemar's Test will be used to explore categorical changes within each treatment group.
Baseline to up to 10 years
Expression of PD-L1 on tumor tissue at recurrence
Time Frame: Up to 10 years
Up to 10 years
Pharmacokinetic analysis of nivolumab
Time Frame: On day 1 of cycles 1-3, 5, 7 and the first 2 follow-up visits
Serum concentration analyses for nivolumab will be performed by validated bio-analytical methods for nivolumab.
On day 1 of cycles 1-3, 5, 7 and the first 2 follow-up visits
Change in patient-reported symptoms and toxicities
Time Frame: Baseline to up to 10 years
Using the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy (NCCN/FACT) Kidney Symptom Index-19 (NFKSI-19) and items from the PRO-CTCAE pool of items measuring patient-reported toxicity. We will describe the severity, interference, and (as appropriate) frequency rates, along with response rates at each time point. Change in symptoms will be tested using a two-sided Wilcoxon rank sum test with Type I error of 3%. Change in physical function will be tested using a two-sided Wilcoxon rank sum test with Type I error of 1%. Changes in NFKSI-19 and PROMIS Physical Function scores from baseline to pre-nephrectomy among patients randomized to nivolumab and will be explored using a Wilcoxon signed rank test. Differences in scores post-nephrectomy between the arms will be described and tested using a Wilcoxon rank-sum test. Differences in the pattern of change over time in NFKSI-19 and PROMIS Physical Function scores will be examined using mixed effects models.
Baseline to up to 10 years
Absolute T cell clonotype abundance
Time Frame: Up to 10 years
Will be determined by assessing the number of unique clonotypes identified. The data will be summarized descriptively and graphically.
Up to 10 years
Change in T cell repertoire
Time Frame: From diagnosis to on therapy or to time of recurrence, assessed up to 10 years
Morisita's distance will be used as utilized by Cha and colleagues. Morisita's distance ranges from 0-1. Zero indicates minimal change in T cell repertoire (TCR) repertoire size (number of unique clonotypes) and 1 indicates maximal change after treatment.
From diagnosis to on therapy or to time of recurrence, assessed up to 10 years
T cell receptor (TCR) diversity using change in repertoire size per patient
Time Frame: Baseline to up to 10 years
The top 25% of unique clonotypes will be identified by sorting for clone frequency. Fold change after recurrence will be measured and plotted on a logarithmic scale.
Baseline to up to 10 years
Change in cytokine levels in patients randomized to the nivolumab arm
Time Frame: Baseline to up to 10 years
Differences in RFS between patients with and without robust CD8 infiltration will be explored. A Cox proportional hazards model will be used to test the interaction between treatment and cytokine changes.
Baseline to up to 10 years

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

Collaborators

Canadian Cancer Trials Group

Investigators

  • Principal Investigator: Lauren Harshman, ECOG-ACRIN Cancer Research Group

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

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)

April 28, 2017

Primary Completion (Actual)

May 24, 2023

Study Completion (Estimated)

October 4, 2024

Study Registration Dates

First Submitted

February 15, 2017

First Submitted That Met QC Criteria

February 15, 2017

First Posted (Actual)

February 16, 2017

Study Record Updates

Last Update Posted (Estimated)

October 9, 2023

Last Update Submitted That Met QC Criteria

October 6, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2016-00326 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180820 (U.S. NIH Grant/Contract)
  • EA8143 (Other Identifier: CTEP)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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