Trametinib in Treating Patients With Recurrent or Progressive Low-Grade Ovarian Cancer or Peritoneal Cavity Cancer

A Randomized Phase II/III Study to Assess the Efficacy of Trametinib (GSK 1120212) in Patients With Recurrent or Progressive Low-Grade Serous Ovarian Cancer or Peritoneal Cancer

This phase II/III trial studies how well trametinib works and compares it to standard treatment with either letrozole, tamoxifen, paclitaxel, pegylated liposomal doxorubicin, or topotecan in treating patients with low-grade ovarian cancer or peritoneal cavity cancer that has come back (recurrent), become worse (progressive), or spread to other parts of the body. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether trametinib is more effective than standard therapy in treating patients with ovarian or peritoneal cavity cancer.

Study Overview

• Status: Completed
• Conditions: Ovarian Serous Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Ovarian Low Grade Serous Adenocarcinoma; Borderline Ovarian Serous Tumor; Micropapillary Serous Carcinoma; Recurrent Primary Peritoneal Serous Adenocarcinoma
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Pegylated Liposomal Doxorubicin Hydrochloride; Drug: Trametinib Dimethyl Sulfoxide; Drug: Paclitaxel; Drug: Topotecan; Drug: Letrozole; Drug: Tamoxifen Citrate

Detailed Description

PRIMARY OBJECTIVE:

I. To estimate the progression-free survival (PFS) hazard ratio of trametinib compared to that of "commercially available therapies" consisting of one of five commercially available agents in women with recurrent low-grade serous carcinoma of the ovary or peritoneum previously treated with platinum-based chemotherapy.

SECONDARY OBJECTIVES:

I. To determine the nature, frequency and maximum degree of toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4 for each treatment arm.

II. To determine the quality of life, as assessed by the Functional Assessment of Cancer Therapy-Ovarian (FACT-O).

IIa. To compare trametinib to the control arm with regard to patients' self-reported acute (up to post-cycle 6) quality of life as measured by the FACT-O-Trial Outcome Index (TOI).

IIb. To compare trametinib to the control arm with regard to patients' self-reported acute (up to post-cycle 6) neurotoxicity as measured by the FACT-Gynecologic Oncology Group (GOG)-Neurotoxicity (NTX).

III. To estimate the objective response rate (RR) of patients in each treatment arm.

IV. To test whether high expression of pERK, as quantified by immunohistochemistry (IHC), is associated with better prognosis (RR or PFS) among patients receiving the randomized treatment.

V. To test whether genetic changes associated with MAPK pathway activation (KRAS, NRAS, HRAS, BRAF, MEK, ERBB2 or NF1) are associated with improved prognosis (RR or PFS) among patients receiving the randomized treatment.

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

ARM A: Patients receive clinician's choice of either letrozole orally (PO) once daily (QD) on days 1-28, tamoxifen citrate PO twice daily (BID) on days 1-28, paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15, pegylated liposomal doxorubicin hydrochloride (PLD) IV over 1 hour on day 1, or topotecan IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients developing progressive disease may cross over to Arm B.

ARM B: Patients receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

• Study Type: Interventional
• Enrollment (Actual): 260
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden NHS Foundation Trust-Chelsea
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham City Hospital
  • England
    • Bristol, England, United Kingdom, BS2 8ED
      • Bristol Royal Infirmary
    • Cambridge, England, United Kingdom, CB2 0QQ
      • Addenbrookes Hospital-Medical School
    • London, England, United Kingdom, EC1A 7BE
      • Saint Bartholomew's Hospital
    • London, England, United Kingdom, W12 0HS
      • Hammersmith Hospital
    • London, England, United Kingdom, WC1E 6AG
      • University College London Hospital
    • Manchester, England, United Kingdom, M20 4BX
      • Christie Hospital
    • Somerset, England, United Kingdom, TA1 5DA
      • Musgrove Park Hospital
    • West Yorkshire, England, United Kingdom, LS9 7TF
      • Saint James's University Hospital
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom, BT9 7AB
      • Belfast City Hospital
  • Scotland
    • Edinburgh, Scotland, United Kingdom, EH4 2XU
      • Western General Hospital
    • Glasgow, Scotland, United Kingdom, G12 0YN
      • Beatson Oncology Center
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35805
      • Tennessee Valley Gynecologic Oncology
  • Alaska
    • Anchorage, Alaska, United States, 98508
      • Anchorage Associates in Radiation Medicine
    • Anchorage, Alaska, United States, 99508
      • Alaska Breast Care and Surgery LLC
    • Anchorage, Alaska, United States, 99508
      • Alaska Oncology and Hematology LLC
    • Anchorage, Alaska, United States, 99508
      • Alaska Women's Cancer Care
    • Anchorage, Alaska, United States, 99508
      • Anchorage Oncology Centre
    • Anchorage, Alaska, United States, 99508
      • Katmai Oncology Group
    • Anchorage, Alaska, United States, 99508
      • Providence Alaska Medical Center
    • Anchorage, Alaska, United States, 99504
      • Anchorage Radiation Therapy Center
    • Fairbanks, Alaska, United States, 99701
      • Fairbanks Memorial Hospital
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Banner University Medical Center - Tucson
    • Tucson, Arizona, United States, 85719
      • University of Arizona Cancer Center-North Campus
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • CHI Saint Vincent Cancer Center Hot Springs
  • California
    • Auburn, California, United States, 95602
      • Sutter Auburn Faith Hospital
    • Auburn, California, United States, 95603
      • Sutter Cancer Centers Radiation Oncology Services-Auburn
    • Berkeley, California, United States, 94704
      • Alta Bates Summit Medical Center-Herrick Campus
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    • Burlingame, California, United States, 94010
      • Mills-Peninsula Medical Center
    • Cameron Park, California, United States, 95682
      • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
    • Castro Valley, California, United States, 94546
      • Eden Hospital Medical Center
    • Clovis, California, United States, 93611
      • Community Cancer Institute
    • Clovis, California, United States, 93611
      • University Oncology Associates
    • Davis, California, United States, 95616
      • Sutter Davis Hospital
    • Fremont, California, United States, 94538
      • Palo Alto Medical Foundation-Fremont
    • Modesto, California, United States, 95355
      • Memorial Medical Center
    • Mountain View, California, United States, 94040
      • Palo Alto Medical Foundation-Camino Division
    • Mountain View, California, United States, 94040
      • Palo Alto Medical Foundation-Gynecologic Oncology
    • Novato, California, United States, 94945
      • Sutter Cancer Research Consortium
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Institute Palo Alto
    • Palo Alto, California, United States, 94301
      • Palo Alto Medical Foundation Health Care
    • Roseville, California, United States, 95661
      • Sutter Cancer Centers Radiation Oncology Services-Roseville
    • Roseville, California, United States, 95661
      • Sutter Roseville Medical Center
    • Sacramento, California, United States, 95816
      • Sutter Medical Center Sacramento
    • San Francisco, California, United States, 94158
      • UCSF Medical Center-Mission Bay
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center-Pacific Campus
    • San Jose, California, United States, 95124
      • Stanford Cancer Center South Bay
    • Santa Cruz, California, United States, 95065
      • Palo Alto Medical Foundation-Santa Cruz
    • Santa Rosa, California, United States, 95403
      • Sutter Pacific Medical Foundation
    • Sunnyvale, California, United States, 94086
      • Palo Alto Medical Foundation-Sunnyvale
    • Vallejo, California, United States, 94589
      • Sutter Solano Medical Center/Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Rocky Mountain Cancer Centers-Aurora
    • Aurora, Colorado, United States, 80012
      • The Medical Center of Aurora
    • Boulder, Colorado, United States, 80303
      • Boulder Community Foothills Hospital
    • Boulder, Colorado, United States, 80304
      • Rocky Mountain Cancer Centers-Boulder
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Colorado Springs, Colorado, United States, 80907
      • Rocky Mountain Cancer Centers-Penrose
    • Denver, Colorado, United States, 80218
      • Presbyterian - Saint Lukes Medical Center - Health One
    • Denver, Colorado, United States, 80220
      • Rose Medical Center
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers-Midtown
    • Denver, Colorado, United States, 80220
      • Rocky Mountain Cancer Centers-Rose
    • Denver, Colorado, United States, 80204
      • Denver Health Medical Center
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
    • Denver, Colorado, United States, 80222
      • Western States Cancer Research NCORP
    • Denver, Colorado, United States, 80209
      • The Women's Imaging Center
    • Denver, Colorado, United States, 80206
      • National Jewish Health-Main Campus
    • Denver, Colorado, United States, 80218
      • Saint Joseph Hospital - Cancer Centers of Colorado
    • Denver, Colorado, United States, 80210
      • AdventHealth Porter
    • Durango, Colorado, United States, 81301
      • Mercy Medical Center
    • Durango, Colorado, United States, 81301
      • CommonSpirit Cancer Center Mercy
    • Englewood, Colorado, United States, 80113
      • Mountain Blue Cancer Care Center - Swedish
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
    • Golden, Colorado, United States, 80401
      • Mountain Blue Cancer Care Center
    • Golden, Colorado, United States, 80401
      • National Jewish Health-Western Hematology Oncology
    • Greeley, Colorado, United States, 80631
      • Banner North Colorado Medical Center
    • Greenwood Village, Colorado, United States, 80111
      • Rocky Mountain Cancer Centers-Greenwood Village
    • Lakewood, Colorado, United States, 80228
      • Saint Anthony Hospital
    • Lakewood, Colorado, United States, 80228
      • Rocky Mountain Cancer Centers-Lakewood
    • Littleton, Colorado, United States, 80120
      • Rocky Mountain Cancer Centers-Littleton
    • Littleton, Colorado, United States, 80122
      • AdventHealth Littleton
    • Lone Tree, Colorado, United States, 80124
      • Sky Ridge Medical Center
    • Lone Tree, Colorado, United States, 80124
      • Rocky Mountain Cancer Centers-Sky Ridge
    • Longmont, Colorado, United States, 80501
      • Longmont United Hospital
    • Longmont, Colorado, United States, 80501
      • Rocky Mountain Cancer Centers-Longmont
    • Loveland, Colorado, United States, 80539
      • Banner McKee Medical Center
    • Parker, Colorado, United States, 80138
      • Rocky Mountain Cancer Centers-Parker
    • Parker, Colorado, United States, 80138
      • AdventHealth Parker
    • Pueblo, Colorado, United States, 81004
      • Saint Mary Corwin Medical Center
    • Pueblo, Colorado, United States, 81008
      • Rocky Mountain Cancer Centers - Pueblo
    • Thornton, Colorado, United States, 80260
      • Rocky Mountain Cancer Centers-Thornton
    • Thornton, Colorado, United States, 80260
      • National Jewish Health-Northern Hematology Oncology
    • Wheat Ridge, Colorado, United States, 80401
      • Intermountain Health Lutheran Hospital
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • Smilow Cancer Hospital Care Center at Saint Francis
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
    • New Britain, Connecticut, United States, 06050
      • The Hospital of Central Connecticut
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20016
      • Sibley Memorial Hospital
  • 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
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Sylvester Cancer Center
    • Miami, Florida, United States, 33136
      • Jackson Memorial Hospital-Holtz Children's Hospital
    • Plantation, Florida, United States, 33324
      • UM Sylvester Comprehensive Cancer Center at Plantation
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
    • Columbus, Georgia, United States, 31904
      • John B Amos Cancer Center
    • Cumming, Georgia, United States, 30041
      • Northside Hospital-Forsyth
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center-Gainesville
    • Savannah, Georgia, United States, 31405
      • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
    • Boise, Idaho, United States, 83712
      • Saint Luke's Cancer Institute - Boise
    • Caldwell, Idaho, United States, 83605
      • Saint Alphonsus Cancer Care Center-Caldwell
    • Coeur d'Alene, Idaho, United States, 83814
      • Kootenai Health - Coeur d'Alene
    • Emmett, Idaho, United States, 83617
      • Walter Knox Memorial Hospital
    • Fruitland, Idaho, United States, 83619
      • Saint Luke's Cancer Institute - Fruitland
    • Meridian, Idaho, United States, 83642
      • Idaho Urologic Institute-Meridian
    • Meridian, Idaho, United States, 83642
      • Saint Luke's Cancer Institute - Meridian
    • Nampa, Idaho, United States, 83687
      • Saint Alphonsus Cancer Care Center-Nampa
    • 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
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60625
      • Swedish Covenant Hospital
    • Danville, Illinois, United States, 61832
      • Carle at The Riverfront
    • Effingham, Illinois, United States, 62401
      • Carle Physician Group-Effingham
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem-Evanston Hospital
    • Evanston, Illinois, United States, 60202
      • Saint Francis Hospital
    • 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
    • Hinsdale, Illinois, United States, 60521
      • Sudarshan K Sharma MD Limited-Gynecologic Oncology
    • Mattoon, Illinois, United States, 61938
      • Carle Physician Group-Mattoon/Charleston
    • Mount Vernon, Illinois, United States, 62864
      • SSM Health Good Samaritan
    • Skokie, Illinois, United States, 60076
      • North Shore Medical Center
    • 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
    • Crown Point, Indiana, United States, 46307
      • Michiana Hematology Oncology PC-Crown Point
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Elkhart, Indiana, United States, 46514
      • Michiana Hematology Oncology PC-Elkhart
    • Elkhart, Indiana, United States, 46514-2098
      • Elkhart Clinic
    • Evansville, Indiana, United States, 47713
      • Deaconess Clinic Downtown
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46260
      • Ascension Saint Vincent Indianapolis Hospital
    • Kokomo, Indiana, United States, 46904
      • Community Howard Regional Health
    • La Porte, Indiana, United States, 46350
      • IU Health La Porte Hospital
    • Michigan City, Indiana, United States, 46360
      • Franciscan Saint Anthony Health-Michigan City
    • Michigan City, Indiana, United States, 46360
      • Woodland Cancer Care Center
    • Mishawaka, Indiana, United States, 46545
      • Memorial Regional Cancer Center Day Road
    • Mishawaka, Indiana, United States, 46545
      • Michiana Hematology Oncology PC-Mishawaka
    • Mishawaka, Indiana, United States, 46545
      • Saint Joseph Regional Medical Center-Mishawaka
    • Newburgh, Indiana, United States, 47630
      • Chancellor Center for Oncology
    • Plymouth, Indiana, United States, 46563
      • Michiana Hematology Oncology PC-Plymouth
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46617
      • South Bend Clinic
    • Westville, Indiana, United States, 46391
      • Michiana Hematology Oncology PC-Westville
  • Iowa
    • 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
    • Council Bluffs, Iowa, United States, 51503
      • Alegent Health Mercy Hospital
    • Creston, Iowa, United States, 50801
      • Greater Regional Medical Center
    • 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, 50314
      • Broadlawns Medical Center
    • Des Moines, Iowa, United States, 50316
      • Iowa Lutheran Hospital
    • 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
    • West Des Moines, Iowa, United States, 50266-7700
      • Methodist West Hospital
    • West Des Moines, Iowa, United States, 50266
      • Mercy Medical Center-West Lakes
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Flaget Memorial Hospital
    • Corbin, Kentucky, United States, 40701
      • Commonwealth Cancer Center-Corbin
    • Lexington, Kentucky, United States, 40504
      • Saint Joseph Radiation Oncology Resource Center
    • Lexington, Kentucky, United States, 40509
      • Saint Joseph Hospital East
    • London, Kentucky, United States, 40741
      • Saint Joseph London
    • Louisville, Kentucky, United States, 40202
      • The James Graham Brown Cancer Center at University of Louisville
    • Louisville, Kentucky, United States, 40202
      • Jewish Hospital
    • Louisville, Kentucky, United States, 40245
      • UofL Health Medical Center Northeast
    • Louisville, Kentucky, United States, 40215
      • Saints Mary and Elizabeth Hospital
    • Shepherdsville, Kentucky, United States, 40165
      • Jewish Hospital Medical Center South
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70817
      • Woman's Hospital
  • Maine
    • Scarborough, Maine, United States, 04074
      • MaineHealth Maine Medical Center- Scarborough
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
    • Bethesda, Maryland, United States, 20889-5600
      • Walter Reed National Military Medical Center
  • Massachusetts
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Trinity Health Saint Joseph Mercy Hospital Ann Arbor
    • Battle Creek, Michigan, United States, 49017
      • Bronson Battle Creek
    • Brighton, Michigan, United States, 48114
      • Trinity Health IHA Medical Group Hematology Oncology - Brighton
    • Brighton, Michigan, United States, 48114
      • Trinity Health Medical Center - Brighton
    • Canton, Michigan, United States, 48188
      • Trinity Health IHA Medical Group Hematology Oncology - Canton
    • Canton, Michigan, United States, 48188
      • Trinity Health Medical Center - Canton
    • Caro, Michigan, United States, 48723
      • Caro Cancer Center
    • Chelsea, Michigan, United States, 48118
      • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
    • Chelsea, Michigan, United States, 48118
      • Chelsea Hospital
    • Clarkston, Michigan, United States, 48346
      • Hematology Oncology Consultants-Clarkston
    • Clarkston, Michigan, United States, 48346
      • Newland Medical Associates-Clarkston
    • Dearborn, Michigan, United States, 48124
      • Corewell Health Dearborn Hospital
    • Detroit, Michigan, United States, 48236
      • Henry Ford Health Saint John Hospital
    • East China Township, Michigan, United States, 48054
      • Henry Ford River District Hospital
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesee Hematology Oncology PC
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Flint, Michigan, United States, 48503
      • Cancer Hematology Centers - Flint
    • 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
    • Kalamazoo, Michigan, United States, 49048
      • Beacon Kalamazoo
    • Lansing, Michigan, United States, 48912
      • University of Michigan Health - Sparrow Lansing
    • Livonia, Michigan, United States, 48154
      • Trinity Health Saint Mary Mercy Livonia Hospital
    • Livonia, Michigan, United States, 48154
      • Hope Cancer Clinic
    • Macomb, Michigan, United States, 48044
      • Henry Ford Warren Hospital - Breast Macomb
    • Macomb, Michigan, United States, 48044
      • Henry Ford Saint John Hospital - Macomb Medical
    • Marlette, Michigan, United States, 48453
      • Saint Mary's Oncology/Hematology Associates of Marlette
    • Monroe, Michigan, United States, 48162
      • Monroe Cancer Center
    • Muskegon, Michigan, United States, 49444
      • Trinity Health Muskegon Hospital
    • Niles, Michigan, United States, 49120
      • Corewell Health Lakeland Hospitals - Niles Hospital
    • Pontiac, Michigan, United States, 48341
      • Hope Cancer Center
    • Pontiac, Michigan, United States, 48341
      • Newland Medical Associates-Pontiac
    • Pontiac, Michigan, United States, 48341
      • Trinity Health Saint Joseph Mercy Oakland Hospital
    • Pontiac, Michigan, United States, 48341
      • Michigan Healthcare Professionals Pontiac
    • Port Huron, Michigan, United States, 48060
      • Lake Huron Medical Center
    • 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, 48604
      • Oncology Hematology Associates of Saginaw Valley PC
    • Saginaw, Michigan, United States, 48601
      • MyMichigan Medical Center Saginaw
    • Saint Joseph, Michigan, United States, 49085
      • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
    • Saint Joseph, Michigan, United States, 49085
      • Corewell Health Lakeland Hospitals - Saint Joseph Hospital
    • Sterling Heights, Michigan, United States, 48312
      • Bhadresh Nayak MD PC-Sterling Heights
    • Tawas City, Michigan, United States, 48764
      • MyMichigan Medical Center Tawas
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Warren, Michigan, United States, 48088
      • Advanced Breast Care Center PLLC
    • Warren, Michigan, United States, 48093
      • Macomb Hematology Oncology PC
    • Warren, Michigan, United States, 48093
      • Henry Ford Madison Heights Hospital - Breast
    • Warren, Michigan, United States, 48093
      • Henry Ford Health Warren Hospital
    • Warren, Michigan, United States, 48093
      • Henry Ford Warren Hospital - GLCMS
    • West Branch, Michigan, United States, 48661
      • Saint Mary's Oncology/Hematology Associates of West Branch
    • Wyoming, Michigan, United States, 49519
      • University of Michigan Health - West
    • Ypsilanti, Michigan, United States, 48197
      • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
    • Ypsilanti, Michigan, United States, 48106
      • Huron Gastroenterology PC
  • Minnesota
    • Bemidji, Minnesota, United States, 56601
      • Sanford Joe Lueken Cancer Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Bolivar, Missouri, United States, 65613
      • Central Care Cancer Center - Bolivar
    • Branson, Missouri, United States, 65616
      • Cox Cancer Center Branson
    • Joplin, Missouri, United States, 64804
      • Freeman Health System
    • Joplin, Missouri, United States, 64804
      • Mercy Hospital Joplin
    • Rolla, Missouri, United States, 65401
      • Mercy Clinic-Rolla-Cancer and Hematology
    • Rolla, Missouri, United States, 65401
      • Phelps Health Delbert Day Cancer Institute
    • Saint Joseph, Missouri, United States, 64506
      • Heartland Regional Medical Center
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
    • St Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • St Louis, Missouri, United States, 63109
      • Mercy Infusion Center - Chippewa
    • St Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
  • 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
    • Kearney, Nebraska, United States, 68847
      • CHI Health Good Samaritan
    • Kearney, Nebraska, United States, 68845
      • Fred and Pamela Buffett Cancer Center - Kearney
    • Lincoln, Nebraska, United States, 68510
      • Saint Elizabeth Regional Medical Center
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
    • 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, 68122
      • Hematology and Oncology Consultants PC
    • Papillion, Nebraska, United States, 68046
      • Midlands Community Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Women's Cancer Center of Nevada
    • Reno, Nevada, United States, 89502
      • Renown Regional Medical Center
    • Reno, Nevada, United States, 89502
      • Center of Hope at Renown Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University 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
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Southwest Gynecologic Oncology Associates Inc
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Cancer Center
    • Albuquerque, New Mexico, United States, 87131
      • New Mexico Cancer Research Alliance
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10065
      • NYP/Weill Cornell Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester
    • White Plains, New York, United States, 10601
      • Dickstein Cancer Treatment Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Lineberger Comprehensive Cancer Center
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Presbyterian Medical Center
    • Charlotte, North Carolina, United States, 28207
      • Oncology Specialists of Charlotte
    • Charlotte, North Carolina, United States, 28262
      • Southern Oncology Specialists-Charlotte
    • Clinton, North Carolina, United States, 28328
      • Southeastern Medical Oncology Center-Clinton
    • Clinton, North Carolina, United States, 28328
      • Sampson Radiation Oncology
    • 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
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Radiation Oncology
    • Huntersville, North Carolina, United States, 28078
      • Novant Health Cancer Institute - Huntersville
    • Huntersville, North Carolina, United States, 28078
      • Southern Oncology Specialists-Huntersville
    • Jacksonville, North Carolina, United States, 28546
      • Southeastern Medical Oncology Center-Jacksonville
    • Jacksonville, North Carolina, United States, 28546
      • Onslow Memorial Hospital
    • Matthews, North Carolina, United States, 28105
      • Matthews Radiation Oncology Center
    • Matthews, North Carolina, United States, 28105
      • Novant Health Cancer Institute - Matthews
    • Mooresville, North Carolina, United States, 28117
      • Novant Health Cancer Institute - Mooresville
    • Raleigh, North Carolina, United States, 27607
      • Duke Women's Cancer Care Raleigh
    • Raleigh, North Carolina, United States, 27609
      • Duke Cancer Center Raleigh
  • 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
    • Beachwood, Ohio, United States, 44122
      • UHHS-Chagrin Highlands Medical Center
    • Belpre, Ohio, United States, 45714
      • Strecker Cancer Center-Belpre
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • 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
    • Cincinnati, Ohio, United States, 45247
      • TriHealth Cancer Institute-Westside
    • Cincinnati, Ohio, United States, 45255
      • TriHealth Cancer Institute-Anderson
    • 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, 43215
      • Grant Medical Center
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health Center West
    • Columbus, Ohio, United States, 43215
      • Columbus NCI Community Oncology Research Program
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Delaware, Ohio, United States, 43015
      • Delaware Health Center-Grady Cancer Center
    • Delaware, Ohio, United States, 43015
      • Delaware Radiation Oncology
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Lancaster, Ohio, United States, 43130
      • Lancaster Radiation Oncology
    • Marietta, Ohio, United States, 45750
      • Marietta Memorial Hospital
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Hospital Cancer Center
    • Mayfield Heights, Ohio, United States, 44124
      • UH Seidman Cancer Center at Landerbrook Health Center
    • Mentor, Ohio, United States, 44060
      • UH Seidman Cancer Center at Lake Health Mentor Campus
    • Mount Vernon, Ohio, United States, 43050
      • Knox Community Hospital
    • Newark, Ohio, United States, 43055
      • Licking Memorial Hospital
    • Newark, Ohio, United States, 43055
      • Newark Radiation Oncology
    • Portsmouth, Ohio, United States, 45662
      • Southern Ohio Medical Center
    • Springfield, Ohio, United States, 45504
      • Springfield Regional Medical Center
    • Sylvania, Ohio, United States, 43560
      • ProMedica Flower Hospital
    • Toledo, Ohio, United States, 43606
      • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
    • Wadsworth, Ohio, United States, 44281
      • University Hospitals Sharon Health Center
    • Westerville, Ohio, United States, 43081
      • Saint Ann's Hospital
    • Westlake, Ohio, United States, 44145
      • UHHS-Westlake Medical 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
    • Tulsa, Oklahoma, United States, 74146
      • Oklahoma Cancer Specialists and Research Institute-Tulsa
  • Oregon
    • Baker City, Oregon, United States, 97814
      • Saint Alphonsus Cancer Care Center-Baker City
    • Bend, Oregon, United States, 97701
      • Saint Charles Health System
    • Clackamas, Oregon, United States, 97015
      • Clackamas Radiation Oncology Center
    • Clackamas, Oregon, United States, 97015
      • Providence Cancer Institute Clackamas Clinic
    • Coos Bay, Oregon, United States, 97420
      • Bay Area Hospital
    • Gresham, Oregon, United States, 97030
      • Legacy Mount Hood Medical Center
    • Newberg, Oregon, United States, 97132
      • Providence Newberg Medical Center
    • Ontario, Oregon, United States, 97914
      • Saint Alphonsus Cancer Care Center-Ontario
    • Oregon City, Oregon, United States, 97045
      • Providence Willamette Falls Medical Center
    • Portland, Oregon, United States, 97210
      • Legacy Good Samaritan Hospital and Medical Center
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Jefferson Abington Hospital
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital-Cedar Crest
    • Bethlehem, Pennsylvania, United States, 18017
      • Lehigh Valley Hospital - Muhlenberg
    • Bethlehem, Pennsylvania, United States, 18015
      • Saint Luke's University Hospital-Bethlehem Campus
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Easton, Pennsylvania, United States, 18042
      • Easton Hospital
    • Hazleton, Pennsylvania, United States, 18201
      • Geisinger Medical Center-Cancer Center Hazleton
    • Kittanning, Pennsylvania, United States, 16201
      • Armstrong Center for Medicine and Health
    • Lewisburg, Pennsylvania, United States, 17837
      • Geisinger Medical Oncology-Lewisburg
    • Lewistown, Pennsylvania, United States, 17044
      • Lewistown Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania/Abramson Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15224
      • West Penn Hospital
    • Pottsville, Pennsylvania, United States, 17901
      • Geisinger Cancer Services-Pottsville
    • State College, Pennsylvania, United States, 16801
      • Geisinger Medical Group
    • West Chester, Pennsylvania, United States, 19380
      • Chester County Hospital
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley/Henry Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women and Infants Hospital
  • South Carolina
    • Gaffney, South Carolina, United States, 29341
      • Gibbs Cancer Center-Gaffney
    • Greenville, South Carolina, United States, 29607
      • Saint Francis Cancer Center
    • Greenville, South Carolina, United States, 29601
      • Saint Francis Hospital
    • Greer, South Carolina, United States, 29651
      • Gibbs Cancer Center-Pelham
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Center
    • Union, South Carolina, United States, 29379
      • SMC Center for Hematology Oncology Union
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
    • 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
    • Chattanooga, Tennessee, United States, 37404
      • Memorial Hospital
    • Hixson, Tennessee, United States, 37343
      • Pulmonary Medicine Center of Chattanooga-Hixson
    • Ooltewah, Tennessee, United States, 37363
      • Memorial GYN Plus
  • Texas
    • Bryan, Texas, United States, 77802
      • Saint Joseph Regional Cancer Center
    • Conroe, Texas, United States, 77384
      • MD Anderson in The Woodlands
    • Dallas, Texas, United States, 75235
      • Parkland Memorial Hospital
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Houston, Texas, United States, 77030
      • Memorial Hermann Texas Medical Center
    • Houston, Texas, United States, 77079
      • MD Anderson West Houston
    • League City, Texas, United States, 77573
      • MD Anderson League City
    • Sugar Land, Texas, United States, 77478
      • MD Anderson in Sugar Land
    • Sugar Land, Texas, United States, 77479
      • Houston Methodist Sugar Land Hospital
  • 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, 84106
      • Utah Cancer Specialists-Salt Lake City
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
    • St. George, Utah, United States, 84770
      • Saint George Regional Medical Center
  • Washington
    • Aberdeen, Washington, United States, 98520
      • Providence Regional Cancer System-Aberdeen
    • Anacortes, Washington, United States, 98221
      • Cancer Care Center at Island Hospital
    • Auburn, Washington, United States, 98001
      • MultiCare Auburn Medical Center
    • Bainbridge Island, Washington, United States, 98110
      • Virginia Mason Bainbridge Island Medical Center
    • Bellevue, Washington, United States, 98004
      • Overlake Medical Center
    • Bellevue, Washington, United States, 98005
      • Swedish Cancer Institute-Eastside Oncology Hematology
    • Bellingham, Washington, United States, 98225
      • PeaceHealth Saint Joseph Medical Center
    • Burien, Washington, United States, 98166
      • Highline Medical Center-Main Campus
    • Centralia, Washington, United States, 98531
      • Providence Regional Cancer System-Centralia
    • Edmonds, Washington, United States, 98026
      • Swedish Cancer Institute-Edmonds
    • Enumclaw, Washington, United States, 98022
      • Saint Elizabeth Hospital
    • Everett, Washington, United States, 98201
      • Providence Regional Cancer Partnership
    • Federal Way, Washington, United States, 98002
      • Virginia Mason Federal Way Medical Center
    • Federal Way, Washington, United States, 98003
      • Saint Francis Hospital
    • Gig Harbor, Washington, United States, 98332
      • Tacoma/Valley Radiation Oncology Centers-Gig Harbor
    • Gig Harbor, Washington, United States, 98335
      • MultiCare Gig Harbor Medical Park
    • Issaquah, Washington, United States, 98029
      • Swedish Cancer Institute-Issaquah
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • Kennewick, Washington, United States, 99336
      • Northwest Cancer Clinic
    • Lacey, Washington, United States, 98503
      • Providence Regional Cancer System-Lacey
    • Lakewood, Washington, United States, 98499
      • Saint Clare Hospital
    • Longview, Washington, United States, 98632
      • PeaceHealth Saint John Medical Center
    • Lynnwood, Washington, United States, 98036
      • Virginia Mason Lynnwood Medical Center
    • Port Townsend, Washington, United States, 98368
      • Jefferson Healthcare
    • Poulsbo, Washington, United States, 98370
      • Harrison HealthPartners Hematology and Oncology-Poulsbo
    • Poulsbo, Washington, United States, 98370
      • Peninsula Cancer Center
    • Puyallup, Washington, United States, 98372
      • MultiCare Good Samaritan Hospital
    • Puyallup, Washington, United States, 98372
      • Tacoma/Valley Radiation Oncology Centers-Puyallup
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Seattle, Washington, United States, 98107
      • Swedish Medical Center-Ballard Campus
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center-First Hill
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center - Montlake
    • Seattle, Washington, United States, 98112
      • Kaiser Permanente Washington
    • Seattle, Washington, United States, 98104
      • Minor and James Medical PLLC
    • Seattle, Washington, United States, 98104
      • Pacific Gynecology Specialists
    • Seattle, Washington, United States, 98122-5711
      • Swedish Medical Center-Cherry Hill
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center
    • Seattle, Washington, United States, 98133
      • University of Washington Medical Center - Northwest
    • Seattle, Washington, United States, 98133
      • Women's Cancer Center of Seattle
    • Shelton, Washington, United States, 98584
      • Providence Regional Cancer System-Shelton
    • Silverdale, Washington, United States, 98383
      • Saint Michael Cancer Center
    • Spokane, Washington, United States, 99204
      • MultiCare Deaconess Cancer and Blood Specialty Center - Downtown
    • Spokane, Washington, United States, 99218
      • MultiCare Deaconess Cancer and Blood Specialty Center - North
    • Spokane Valley, Washington, United States, 99216
      • MultiCare Deaconess Cancer and Blood Specialty Center - Valley
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties PLLC
    • Tacoma, Washington, United States, 98405
      • MultiCare Tacoma General Hospital
    • Tacoma, Washington, United States, 98405
      • Tacoma/Valley Radiation Oncology Centers-Saint Joe's
    • Tacoma, Washington, United States, 97405
      • Tacoma/Valley Radiation Oncology Centers-Jackson Hall
    • Tacoma, Washington, United States, 98405
      • Franciscan Research Center-Northwest Medical Plaza
    • Vancouver, Washington, United States, 98686
      • Legacy Salmon Creek Hospital
    • Vancouver, Washington, United States, 98664
      • PeaceHealth Southwest Medical Center
    • Walla Walla, Washington, United States, 99362
      • Providence Saint Mary Regional Cancer Center
    • Yakima, Washington, United States, 98902
      • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
    • Yelm, Washington, United States, 98597
      • Providence Regional Cancer System-Yelm
  • Wisconsin
    • Burlington, Wisconsin, United States, 53105
      • Aurora Cancer Care-Southern Lakes VLCC
    • Fond du Lac, Wisconsin, United States, 54937
      • Aurora Health Center-Fond du Lac
    • 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
    • Janesville, Wisconsin, United States, 53548
      • Mercyhealth Hospital and Cancer Center - Janesville
    • Kenosha, Wisconsin, United States, 53142
      • Aurora Cancer Care-Kenosha South
    • Marinette, Wisconsin, United States, 54143
      • Aurora Bay Area Medical Group-Marinette
    • 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
    • Oshkosh, Wisconsin, United States, 54904
      • Vince Lombardi Cancer Clinic - Oshkosh
    • Racine, Wisconsin, United States, 53406
      • Aurora Cancer Care-Racine
    • Sheboygan, Wisconsin, United States, 53081
      • Vince Lombardi Cancer Clinic-Sheboygan
    • 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
      • Aurora Cancer Care-Waukesha
    • Wauwatosa, Wisconsin, United States, 53226
      • Aurora Cancer Care-Milwaukee West
    • West Allis, Wisconsin, United States, 53227
      • Aurora West Allis Medical Center
  • Wyoming
    • Cheyenne, Wyoming, United States, 82001
      • Cheyenne Regional Medical Center-West
    • 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

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients age greater than 18 with the following tumors are included in the study:

  • Patients initially diagnosed with low-grade serous ovarian or peritoneal carcinoma that recur as low-grade serous carcinoma (invasive micropapillary serous carcinoma or invasive grade I serous carcinomas as defined by GOG, Federation of Obstetricians and Gynecologists [FIGO], World Health Organization [WHO] or Silverberg)
  • Patients initially diagnosed with serous borderline ovarian or peritoneal carcinoma that recur as low-grade serous carcinoma (invasive micropapillary serous carcinoma or invasive grade I serous carcinomas as defined by GOG, FIGO WHO or Silverberg)
• At least 4 weeks must have elapsed since the patient underwent any major surgery (e.g. MAJOR: laparotomy, laparoscopy, thoracotomy, VATS [video assisted thorascopic surgery]); there is no restriction on MINOR procedures: (e.g. central venous catheter placement, ureteral stent placement or exchange, tumor core or fine-needle aspirate [FNA] biopsy)
• Patients must have documented low-grade serous carcinoma; confirmation must occur by prospective pathology review prior to study entry; the prospective pathology review can be done on tissue from the recurrent carcinoma or from original diagnostic specimen
• All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one target lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI), or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI; all imaging studies must be performed within 28 days prior to registration

• Prior therapy

  • Patients must have recurred or progressed following at least one platinum-based chemotherapy regimen
  • Patients may have received an unlimited number of prior therapy regimens
  • Patients may not have received all of the five choices in the "standard therapy" arm
  • Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration
  • Any other prior therapy directed at the malignant tumor, including chemotherapy and radiation therapy, must be discontinued at least 4 weeks prior to registration; any investigational agent must be discontinued at least 28 days prior to registration

• Trametinib, can cause fetal harm when administered to a pregnant woman; women of child-bearing potential (i.e. patients whose reproductive organs remain in place and who have not passed menopause) and men must agree to use a highly effective method of contraception (e.g. hormonal, intrauterine device or; abstinence*) prior to study entry, during the study participation, and for six months after the last dose of the drug; women of child-bearing potential must have a negative serum pregnancy test within 14 days prior to randomization, cannot be breast-feeding, and must agree to use a highly effective form of contraception throughout the treatment period and for 6 months after the last dose of study treatment; 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

  • Abstinence is only acceptable when this is in line with the preferred and usual lifestyle of the patient
• Patients must have the ability to understand and sign an approved informed consent and authorization permitting release of personal health information
• Patients must have a GOG performance status of 0 or 1
• Able to swallow and retain orally-administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption, such as malabsorption syndrome, bowel obstruction, or major resection of the stomach or bowel
• All prior treatment-related toxicities must be CTCAE v4 grade =< 1 (except alopecia) at the time of randomization
• Patients must have a left ventricular ejection fraction >= lower limit of normal by echocardiogram (ECHO) or multigated acquisition scan (MUGA)
• Serum creatinine =< 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault formula) >= 50 mL/min OR 24-hour urine creatinine clearance >= 50 mL/min (within 14 days prior to treatment)
• Bilirubin =< 1.5 times upper limit of normal (within 14 days prior to treatment)
• Alanine aminotransferase (ALT) =< 2.5 times upper limit of normal (within 14 days prior to treatment)
• Aspartate aminotransferase (AST) =< 2.5 times upper limit of normal (within 14 days prior to treatment)
• Albumin >= 2.5 g/dL (within 14 days prior to treatment)
• Prothrombin time (PT) and activated partial thromboplastin time (APTT) =< 1.5 times upper limit of normal (within 14 days prior to treatment)
• Neutrophil count >= 1.5 x 10^9/L (within 14 days prior to treatment)
• Platelet count >= 100 x 10^9/L (within 14 days prior to treatment)
• Hemoglobin >= 9.0 g/dL (within 14 days prior to treatment)
• If letrozole is selected as the control therapy, patients must be postmenopausal, either following bilateral oophorectomy or at least 5 years after spontaneous menopause; patients within 5 years of spontaneous menopause or who have had a hysterectomy without bilateral oophorectomy must have postmenopausal luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels; patients on hormone replacement therapy (HRT) must agree to withdrawal of hormone therapy before letrozole is started

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Use of other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of trametinib or standard of care agent
• If patients have had a potential index lesion radiated, it must have progressed post radiation therapy to be used as a measurable eligibility lesion
• Patients may not have received prior MEK, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), or v-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor therapy

• Current use of a prohibited medication; the following medications or non-drug therapies are prohibited:

  • Patients may not be receiving any other anti-cancer or investigational agents
  • Because the composition, PK, and metabolism of many herbal supplements are unknown, the concurrent use of all herbal supplements is prohibited during the study (including, but not limited to St. John's wort, kava, ephedra [ma huang], gingko biloba, dehydroepiandrosterone [DHEA], yohimbe, saw palmetto, or ginseng)
• Patients with known leptomeningeal or brain metastases or spinal cord compression should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• Patients with a bowel obstruction or any other gastrointestinal condition that might affect absorption of the oral drug should be excluded; this would include patients with inability to swallow and retain orally-administered medication, malabsorption syndrome, or those with a major resection of the stomach or bowels
• Patients with a history of interstitial lung disease or pneumonitis

• Patients with a previous or current malignancy at other sites should be excluded, with the exception of:

  • Curatively treated local tumors such as carcinoma-in-situ of the cervix, basal or squamous cell carcinoma of the skin
  • Tumors for which no relapse has been observed within 5 years
• Known hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (patients with chronic or cleared HBV and HCV infection are eligible); patients with human immunodeficiency virus (HIV) are not eligible if on anti-retroviral medications
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib, or excipients, or to dimethyl sulfoxide (DMSO), or to Cremophor EL (polyoxyethylated castor oil); please note, exclusion for Cremophor is unnecessary unless paclitaxel is the only agent available and the patient randomizes to the conventional therapy option

• Patients with a history or evidence of cardiovascular risk, including any of the following:

  • Left ventricular ejection fraction (LVEF) < lower limit of normal (LLN)
  • Bazett's corrected QT (QTcB) >= 480 msec
  • History or evidence of current clinically significant uncontrolled arrhythmias
  • Exception: Subjects with controlled atrial fibrillation for > 30 days prior to randomization are eligible
  • History of (within 6 months prior to randomization) acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting
  • History or evidence of current >= class II congestive heart failure as defined by New York Heart Association (NYHA)
  • Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy
  • Patients with intra-cardiac defibrillators or permanent pacemakers
  • Known cardiac metastases
• Patients with a history or current evidence/risk of retinal vein occlusion (RVO)
• Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures
• Patients who require use of a concomitant medication that can prolong the QT interval
• Animal reproductive studies have not been conducted with trametinib; therefore, the study drug must not be administered to pregnant women or nursing mothers; women of childbearing potential should be advised to avoid pregnancy and use effective methods of contraception; if a female patient or a female partner of a patient becomes pregnant while the patient receives trametinib, the potential hazard to the fetus should be explained to the patient and partner (as applicable)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A (letrozole, tamoxifen, paclitaxel, PLD, topotecan); Patients receive clinician's choice of either letrozole PO QD on days 1-28, tamoxifen citrate PO BID on days 1-28, paclitaxel IV over 1 hour on days 1, 8, and 15, pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 1, or topotecan IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients developing progressive disease may cross over to Arm B.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Drug: Pegylated Liposomal Doxorubicin Hydrochloride; Given IV; Other Names: ATI-0918; Caelyx; Doxil; Doxilen; Doxorubicin HCl Liposome; Duomeisu; Evacet; LipoDox; Liposomal Adriamycin; Liposomal-Encapsulated Doxorubicin; Pegylated Doxorubicin HCl Liposome; S-Liposomal Doxorubicin; Stealth Liposomal Doxorubicin; TLC D-99; Dox-SL; Doxorubicin HCl Liposomal; Doxorubicin Hydrochloride Liposome; Lipodox 50; Liposomal Doxorubicin Hydrochloride; Pegylated Liposomal Doxorubicin; Drug: Paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat; Drug: Topotecan; Given IV; Other Names: Hycamptamine; Topotecan Lactone; Drug: Letrozole; Given PO; Other Names: CGS 20267; Femara; Fempro; CGS-20267; CGS20267; Drug: Tamoxifen Citrate; Given PO; Other Names: Nolvadex; TAM; Soltamox; Apo-Tamox; Clonoxifen; Dignotamoxi; Ebefen; Emblon; Estroxyn; Fentamox; Gen-Tamoxifen; Genox; ICI 46,474; ICI-46474; Jenoxifen; Kessar; Ledertam; Lesporene; Nolgen; Noltam; Nolvadex-D; Nourytam; Novo-Tamoxifen; Novofen; Noxitem; Oestrifen; Oncotam; PMS-Tamoxifen; Tamax; Tamaxin; Tamifen; Tamizam; Tamofen; Tamoxasta; Tamoxifeni Citras; Zemide; ICI 46474; ICI46474
Experimental: Arm B (trametinib); Patients receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Drug: Trametinib Dimethyl Sulfoxide; Given PO; Other Names: Mekinist; Meqsel; Spexotras

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	Progression free survival (PFS) was defined as the number of months between study enrollment and documentation of disease progression (RECIST 1.1) or death from any cause. Patients still alive and disease free at the last followup were censored on the date of last CT Scan.Participants were analyzed based on their group of assignment. Patients on Arm A who progressed were permitted to receive Arm B treatment. Study time for Arm A patients who crossed over was not included in the PFS endpoint definition.	Time from study entry to time of progression or death, an average of 7 months for arm A and 13 months for arm B

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (AEs)	Number of treated patients with Adverse Events (grade 3 or higher) observed while receiving randomized therapy. Excludes AEs observed among control patients treated with trametinib after crossover.Participants were analyzed based on their group of assignment. Patients on Arm A who progressed were permitted to receive Arm B treatment. Study time for Arm A patients who crossed over was not included in the AE endpoint definition.	During treatment period and up to 100 days after stopping the study treatment
Overall Survival	Overall survival (OS) was defined as the number of months between study enrollment and death from any cause. Patients still alive at the last follow-up were censored on the date of last contact. Patients with disease progression on the Control arm were allowed to cross over to the trametinib arm. Per the protocol, the intent-to-treat OS analysis was not adjusted for crossover.	Time from study entry to time of death or date of last contact, an average of 29 months for arm A and 37 months for arm B
Objective Tumor Response Rate (Complete Response and Partial Response)	The Response Rates were estimated as the binomial proportion of patients with Best Overall Response of Complete or Partial response according to RECIST 1.1 criteria.	Time from study entry to time of progression or death, an average of 7 months for arm A and 13 months for arm B
Patients Reported Acute Quality of Life	Patient reported quality of life was measured with the Treatment Outcome Index (TOI) of the Functional Assessment of Cancer Therapy for ovarian cancer (FACT-O TOI). The FACT-O TOI is a scale for assessing general QOL of ovarian cancer patients. It consists of three subscales: Physical Well Being (7 items), Functional Well Being (7 items), and Ovarian Cancer subscale (11 items). . The FACT-O TOI score is calculated as the sum of the subscale scores if more than 80% of the FACT-O TOI items provide valid answers and all of the component subscales have valid scores. The FACT-O TOI score ranges 0-100 with a large score suggesting better QOL. Participants were analyzed based on their group of assignment. Patients on Arm A who progressed were permitted to receive Arm B treatment. Study time for Arm A patients who crossed over was not included in the quality of life endpoint definition	1. baseline (prior to cycle 1), 12 weeks (prior to cycle 4), 24 weeks (4 weeks post cycle 6), 36 weeks post cycle 1, 52 weeks post cycle 1.
Patient Reported Acute Peripheral Neuropathy Symptoms	Patient reported peripheral neuropathy symptoms was measured with the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - neurotoxicity subscale (short version) (FACT/GOG-Ntx subscale). The FACT/GOG-Ntx subscale contains 4 items. Each item was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). According to the FACIT measurement system, the Ntx score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the scale. The Ntx score ranges 0-16 with a large score suggesting less peripheral neuropathy symptoms	Up to 52 weeks
Progression Free Survival	Progression free survival (PFS) was defined as the number of months between study enrollment and documentation of disease progression (RECIST 1.1) or death from any cause. Patients still alive and disease free at the last followup were censored on the date of last CT Scan. RECIST v1.1 defines progression as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.	Time from study entry to time of progression or death, an average of 7 months for SOC and 13 months for the treatment (Trametinib) arm.
pERK Expression	Will be quantified using the H-score derived from the immunohistochemistry analysis of patient tumor tissue and is expected to present as a continuous measure. will consider the prognostic and predictive abilities of pERK relative to objective response rate (ORR) or PFS. Analysis of the dichotomous markers will be supported by Kaplan Meier plots, and forest plots of the odds-ratio and hazard ratio estimates. Duration of response will be depicted using swimmer plots, with median duration estimated using Kaplan Meier methods. The multivariable models will include covariate adjustment for geographic region, performance status and number of prior regimens, presented using effect coding. The adjusted hazard- and odds- ratio estimates from the multivariable models will be supported by nominal p-values and 2-sided, 95% confidence intervals. Confidence intervals will be interpreted as the plausible range of values for the true (unobserved) ratio that is supported by the data.	Baseline

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: NRG Oncology
• Investigators: Principal Investigator: David M Gershenson, NRG Oncology

Publications and helpful links

General Publications

• Gershenson DM, Miller A, Brady WE, Paul J, Carty K, Rodgers W, Millan D, Coleman RL, Moore KN, Banerjee S, Connolly K, Secord AA, O'Malley DM, Dorigo O, Gaillard S, Gabra H, Slomovitz B, Hanjani P, Farley J, Churchman M, Ewing A, Hollis RL, Herrington CS, Huang HQ, Wenzel L, Gourley C. Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial. Lancet. 2022 Feb 5;399(10324):541-553. doi: 10.1016/S0140-6736(21)02175-9.

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2014
• Primary Completion (Actual): April 4, 2019
• Study Completion (Actual): October 27, 2025

Study Registration Dates

• First Submitted: March 28, 2014
• First Submitted That Met QC Criteria: March 28, 2014
• First Posted (Estimated): April 2, 2014

Study Record Updates

• Last Update Posted (Estimated): November 13, 2025
• Last Update Submitted That Met QC Criteria: October 29, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Cystadenocarcinoma; Neoplasms, Cystic, Mucinous, and Serous; Cystadenocarcinoma, Serous; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Carbohydrates; Camptothecin; Alkaloids; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Taxoids; Cyclodecanes; Diterpenes; Benzene Derivatives; Health Care Economics and Organizations; Nitriles; Anthracyclines; Naphthacenes; Aminoglycosides; Daunorubicin; Triazoles; Stilbenes; Benzylidene Compounds; Economics; Letrozole; Doxorubicin; Paclitaxel; Tamoxifen; Topotecan; trametinib; liposomal doxorubicin; Taxes
• Other Study ID Numbers: NCI-2014-00629 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180868 (U.S. NIH Grant/Contract); P50CA083639 (U.S. NIH Grant/Contract); GOG-0281 (Other Identifier: CTEP)