Comparison of Standard of Care Treatment With a Triplet Combination of Targeted Immunotherapeutic Agents

A Randomized Phase II Trial of Triplet Therapy (A PD-L1 Inhibitor Durvalumab (MEDI4736) in Combination With Olaparib and Cediranib) Compared to Olaparib and Cediranib or Durvalumab (MEDI4736) and Cediranib or Standard of Care Chemotherapy in Women With Platinum-Resistant Recurrent Epithelial Ovarian Cancer, Primary Peritoneal or Fallopian Cancer Who Have Received Prior Bevacizumab

This phase II trial studies the possible benefits of treatment with different combinations of the drugs durvalumab, olaparib and cediranib vs. the usual treatment in patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back after a period of improvement with platinum therapy (recurrent platinum resistant). Usual treatment is the type of treatment most patients with this condition receive if they are not part of a clinical study. Combination therapies studied in this trial include MEDI4736 (durvalumab) plus olaparib and cediranib, durvalumab and cediranib, or olaparib and cediranib. Monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumors cells to grow and spread. Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Cediranib may stop the growth of tumor cells by blocking VEGF (an enzyme). needed for cell growth. Giving different combinations of durvalumab, olaparib and cediranib may work better in increasing the duration of time that the cancer does not progress compared to the usual treatment.

Study Overview

• Status: Active, not recruiting
• Conditions: Ovarian Seromucinous Carcinoma; Recurrent Ovarian High Grade Serous Adenocarcinoma; Recurrent Platinum-Resistant Ovarian Carcinoma; Fallopian Tube Mucinous Adenocarcinoma; Recurrent Fallopian Tube Clear Cell Adenocarcinoma; Recurrent Fallopian Tube Endometrioid Adenocarcinoma; Recurrent Fallopian Tube Undifferentiated Carcinoma; Recurrent Ovarian Clear Cell Adenocarcinoma; Recurrent Ovarian Endometrioid Adenocarcinoma; Recurrent Ovarian Undifferentiated Carcinoma; Recurrent Platinum-Resistant Fallopian Tube Carcinoma; Recurrent Platinum-Resistant Primary Peritoneal Carcinoma; Recurrent Primary Peritoneal Clear Cell Adenocarcinoma; Recurrent Primary Peritoneal Endometrioid Adenocarcinoma; Recurrent Primary Peritoneal Undifferentiated Carcinoma; Platinum-Refractory Fallopian Tube Carcinoma; Platinum-Refractory Ovarian Carcinoma; Platinum-Refractory Primary Peritoneal Carcinoma; Recurrent Fallopian Tube High Grade Serous Adenocarcinoma; Recurrent Fallopian Tube Mucinous Adenocarcinoma; Recurrent Fallopian Tube Transitional Cell Carcinoma; Recurrent Low Grade Fallopian Tube Serous Adenocarcinoma; Recurrent Ovarian Low Grade Serous Adenocarcinoma; Recurrent Ovarian Mucinous Adenocarcinoma; Recurrent Ovarian Seromucinous Carcinoma; Recurrent Ovarian Transitional Cell Carcinoma; Recurrent Primary Peritoneal High Grade Serous Adenocarcinoma; Recurrent Primary Peritoneal Low Grade Serous Adenocarcinoma; Recurrent Primary Peritoneal Transitional Cell Carcinoma; Refractory Fallopian Tube Clear Cell Adenocarcinoma; Refractory Fallopian Tube Endometrioid Adenocarcinoma; Refractory Fallopian Tube High Grade Serous Adenocarcinoma; Refractory Fallopian Tube Mucinous Adenocarcinoma; Refractory Fallopian Tube Transitional Cell Carcinoma; Refractory Fallopian Tube Undifferentiated Carcinoma; Refractory Low Grade Fallopian Tube Serous Adenocarcinoma; Refractory Ovarian Clear Cell Adenocarcinoma; Refractory Ovarian Endometrioid Adenocarcinoma; Refractory Ovarian High Grade Serous Adenocarcinoma; Refractory Ovarian Low Grade Serous Adenocarcinoma; Refractory Ovarian Mucinous Adenocarcinoma; Refractory Ovarian Seromucinous Carcinoma; Refractory Ovarian Transitional Cell Carcinoma; Refractory Ovarian Undifferentiated Carcinoma; Refractory Primary Peritoneal Clear Cell Adenocarcinoma; Refractory Primary Peritoneal Endometrioid Adenocarcinoma; Refractory Primary Peritoneal High Grade Serous Adenocarcinoma; Refractory Primary Peritoneal Low Grade Serous Adenocarcinoma; Refractory Primary Peritoneal Transitional Cell Carcinoma; Refractory Primary Peritoneal Undifferentiated Carcinoma
• Intervention / Treatment: Drug: Pegylated Liposomal Doxorubicin Hydrochloride; Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Drug: Paclitaxel; Procedure: Computed Tomography; Biological: Durvalumab; Drug: Olaparib; Drug: Topotecan Hydrochloride; Procedure: Computed Tomography with Contrast; Drug: Cediranib Maleate; Procedure: Echocardiography; Procedure: Multigated Acquisition Scan

Detailed Description

PRIMARY OBJECTIVE:

I. To assess the efficacy of the combinations durvalumab (MEDI4736) plus olaparib and cediranib, durvalumab (MEDI4736) plus cediranib, or olaparib and cediranib, as measured by progression-free survival (PFS), as compared to physician's choice standard of care chemotherapy, in patients with recurrent platinum-resistant ovarian, primary peritoneal or fallopian tube cancer who had prior bevacizumab.

SECONDARY OBJECTIVES:

I. To assess the efficacy of the combinations durvalumab (MEDI4736) plus olaparib and cediranib, durvalumab (MEDI4736) plus cediranib, or olaparib and cediranib, as measured by overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as compared to physician's choice standard of care chemotherapy, in patients with recurrent platinum-resistant ovarian, primary peritoneal or fallopian tube cancer who had prior bevacizumab.

II. To assess the efficacy of the combinations durvalumab (MEDI4736) plus olaparib and cediranib, durvalumab (MEDI4736) plus cediranib, or olaparib and cediranib, as measured by overall survival (OS), as compared to physician's choice standard of care chemotherapy, in patients with recurrent platinum-resistant ovarian, primary peritoneal or fallopian tube cancer who had prior bevacizumab.

OUTLINE: Patients are randomized to 1 of 4 arms.

ARM I: Patients receive paclitaxel intravenously (IV) over 60 minutes on days 1, 8, and 15, or pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8 and 15 or days 1-5 per the discretion of the treating physician. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening and as clinically indicated on study. Patients also undergo collection of blood and computed tomography (CT) with contrast during screening, and CT or magnetic resonance imaging (MRI) scans throughout the trial.

ARM II: Patients receive durvalumab IV over 60 minutes on day 1, cediranib maleate orally (PO) once daily (QD) Monday through Friday, and olaparib PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.

ARM III: Patients receive durvalumab IV over 60 minutes on day 1 and cediranib maleate PO QD Monday through Friday. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.

ARM IV: Patients receive cediranib maleate PO QD on days 1-28 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.

After completion of study treatment, patients are followed up periodically for up to 5 years.

• Study Type: Interventional
• Enrollment (Actual): 149
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • Bayamon, Puerto Rico, 00959-5060
    • Cancer Center-Metro Medical Center Bayamon
  • Caguas, Puerto Rico, 00726
    • HIMA San Pablo Oncologic Hospital
  • Manati, Puerto Rico, 00674
    • Doctors Cancer Center
  • Ponce, Puerto Rico, 00716
    • Instituto Oncologia Moderna Ponce
  • San Juan, Puerto Rico, 00917
    • San Juan Community Oncology Group
  • San Juan, Puerto Rico, 00927
    • Centro Comprensivo de Cancer de UPR
  • San Juan, Puerto Rico, 00936
    • San Juan City Hospital
• United States
  • 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
    • Goodyear, Arizona, United States, 85338
      • CTCA at Western Regional Medical Center
    • Phoenix, Arizona, United States, 85004
      • Cancer Center at Saint Joseph's
  • Arkansas
    • Fort Smith, Arkansas, United States, 72903
      • Mercy Hospital Fort Smith
    • Hot Springs, Arkansas, United States, 71913
      • CHI Saint Vincent Cancer Center Hot Springs
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Arroyo Grande, California, United States, 93420
      • Mission Hope Medical Oncology - Arroyo Grande
    • 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
    • Cameron Park, California, United States, 95682
      • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
    • Castro Valley, California, United States, 94546
      • Eden Hospital Medical Center
    • Concord, California, United States, 94520
      • John Muir Medical Center-Concord Campus
    • Davis, California, United States, 95616
      • Sutter Davis Hospital
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Fremont, California, United States, 94538
      • Palo Alto Medical Foundation-Fremont
    • Lancaster, California, United States, 93534
      • City of Hope Antelope Valley
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • Los Angeles General Medical Center
    • 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
    • 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, 94115
      • California Pacific Medical Center-Pacific Campus
    • San Luis Obispo, California, United States, 93401
      • Pacific Central Coast Health Center-San Luis Obispo
    • Santa Cruz, California, United States, 95065
      • Palo Alto Medical Foundation-Santa Cruz
    • Santa Maria, California, United States, 93444
      • Mission Hope Medical Oncology - Santa Maria
    • Santa Rosa, California, United States, 95403
      • Sutter Pacific Medical Foundation
    • South Pasadena, California, United States, 91030
      • City of Hope South Pasadena
    • Sunnyvale, California, United States, 94086
      • Palo Alto Medical Foundation-Sunnyvale
    • Upland, California, United States, 91786
      • City of Hope Upland
    • Vacaville, California, United States, 95687
      • Sutter Cancer Centers Radiation Oncology Services-Vacaville
    • Vallejo, California, United States, 94589
      • Sutter Solano Medical Center/Cancer Center
    • Walnut Creek, California, United States, 94598
      • John Muir Medical Center-Walnut Creek
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Rocky Mountain Cancer Centers-Aurora
    • Boulder, Colorado, United States, 80304
      • Rocky Mountain Cancer Centers-Boulder
    • Centennial, Colorado, United States, 80112
      • Rocky Mountain Cancer Centers - Centennial
    • 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, 80210
      • Porter Adventist Hospital
    • Durango, Colorado, United States, 81301
      • Mercy Medical Center
    • Durango, Colorado, United States, 81301
      • Southwest Oncology PC
    • Lakewood, Colorado, United States, 80228
      • Saint Anthony Hospital
    • Littleton, Colorado, United States, 80120
      • Rocky Mountain Cancer Centers-Littleton
    • Littleton, Colorado, United States, 80122
      • Littleton Adventist Hospital
    • 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
      • McKee Medical Center
    • Parker, Colorado, United States, 80138
      • Parker Adventist Hospital
    • Pueblo, Colorado, United States, 81004
      • Saint Mary Corwin Medical Center
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Danbury Hospital
    • Norwalk, Connecticut, United States, 06856
      • Norwalk Hospital
  • Florida
    • Pensacola, Florida, United States, 32504
      • Sacred Heart Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
    • Newnan, Georgia, United States, 30265
      • CTCA at Southeastern Regional Medical Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
    • Honolulu, Hawaii, United States, 96826
      • Kapiolani Medical Center for Women and Children
  • 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, 83686
      • Saint Luke's Cancer Institute - Nampa
    • Nampa, Idaho, United States, 83687
      • Saint Alphonsus Cancer Care Center-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
    • Alton, Illinois, United States, 62002
      • Saint Anthony's Health
    • Aurora, Illinois, United States, 60504
      • Rush - Copley Medical Center
    • Bloomington, Illinois, United States, 61704
      • Illinois CancerCare-Bloomington
    • Canton, Illinois, United States, 61520
      • Illinois CancerCare-Canton
    • Carbondale, Illinois, United States, 62902
      • Memorial Hospital of Carbondale
    • Carterville, Illinois, United States, 62918
      • SIH Cancer Institute
    • Carthage, Illinois, United States, 62321
      • Illinois CancerCare-Carthage
    • Centralia, Illinois, United States, 62801
      • Centralia Oncology Clinic
    • 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
      • John H Stroger Jr Hospital of Cook County
    • Danville, Illinois, United States, 61832
      • Carle at The Riverfront
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Cancer Care Specialists of Illinois - Decatur
    • Dixon, Illinois, United States, 61021
      • Illinois CancerCare-Dixon
    • Effingham, Illinois, United States, 62401
      • Crossroads Cancer Center
    • Effingham, Illinois, United States, 62401
      • Carle Physician Group-Effingham
    • Eureka, Illinois, United States, 61530
      • Illinois CancerCare-Eureka
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem-Evanston Hospital
    • Galesburg, Illinois, United States, 61401
      • Western Illinois Cancer Treatment Center
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Galesburg
    • Geneva, Illinois, United States, 60134
      • Northwestern Medicine Cancer Center Delnor
    • Glenview, Illinois, United States, 60026
      • NorthShore University HealthSystem-Glenbrook Hospital
    • Harvey, Illinois, United States, 60426
      • Ingalls Memorial 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
    • 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
    • Mount Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
    • New Lenox, Illinois, United States, 60451
      • UC Comprehensive Cancer Center at Silver Cross
    • O'Fallon, Illinois, United States, 62269
      • Cancer Care Center of O'Fallon
    • Orland Park, Illinois, United States, 60462
      • University of Chicago Medicine-Orland Park
    • Ottawa, Illinois, United States, 61350
      • Illinois CancerCare-Ottawa Clinic
    • Pekin, Illinois, United States, 61554
      • Illinois CancerCare-Pekin
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peru, Illinois, United States, 61354
      • Illinois CancerCare-Peru
    • Peru, Illinois, United States, 61354
      • Valley Radiation Oncology
    • Princeton, Illinois, United States, 61356
      • Illinois CancerCare-Princeton
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
    • 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
    • Washington, Illinois, United States, 61571
      • Illinois CancerCare - Washington
    • Yorkville, Illinois, United States, 60560
      • Rush-Copley Healthcare Center
    • Zion, Illinois, United States, 60099
      • Midwestern Regional Medical Center
  • Indiana
    • 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
    • Cedar Rapids, Iowa, United States, 52403
      • Mercy Hospital
    • Cedar Rapids, Iowa, United States, 52403
      • Oncology Associates at Mercy Medical Center
    • Clive, Iowa, United States, 50325
      • Mercy Cancer Center-West Lakes
    • Clive, Iowa, United States, 50325
      • Medical Oncology and Hematology Associates-West Des Moines
    • Council Bluffs, Iowa, United States, 51503
      • Alegent Health Mercy Hospital
    • Creston, Iowa, United States, 50801
      • Greater Regional Medical Center
    • 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
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
    • Jefferson, Iowa, United States, 50129
      • McFarland Clinic - Jefferson
    • Marshalltown, Iowa, United States, 50158
      • McFarland Clinic - Marshalltown
    • West Des Moines, Iowa, United States, 50266
      • Mercy Medical Center-West Lakes
  • Kansas
    • Garden City, Kansas, United States, 67846
      • Central Care Cancer Center - Garden City
    • Great Bend, Kansas, United States, 67530
      • Central Care Cancer Center - Great Bend
  • 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
      • 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
      • Our Lady of the Lake Medical Oncology
  • Maine
    • Augusta, Maine, United States, 04330
      • Harold Alfond Center for Cancer Care
    • Brewer, Maine, United States, 04412
      • Lafayette Family Cancer Center-EMMC
    • Scarborough, Maine, United States, 04074
      • Maine Medical Center- Scarborough Campus
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
    • Dearborn, Michigan, United States, 48124
      • Beaumont Hospital - Dearborn
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital-Royal Oak
    • Troy, Michigan, United States, 48085
      • William Beaumont Hospital - Troy
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Burnsville, Minnesota, United States, 55337
      • Minnesota Oncology - Burnsville
    • Cambridge, Minnesota, United States, 55008
      • Cambridge Medical Center
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Maple Grove, Minnesota, United States, 55369
      • Fairview Clinics and Surgery Center Maple Grove
    • Maplewood, Minnesota, United States, 55109
      • Saint John's Hospital - Healtheast
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology PA-Maplewood
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55454
      • Health Partners Inc
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota/Masonic Cancer Center
    • Monticello, Minnesota, United States, 55362
      • Monticello Cancer Center
    • New Ulm, Minnesota, United States, 56073
      • New Ulm Medical Center
    • Princeton, Minnesota, United States, 55371
      • Fairview Northland Medical Center
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Medical Health Center
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Regional Medical Center
    • Stillwater, Minnesota, United States, 55082
      • Lakeview Hospital
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Willmar, Minnesota, United States, 56201
      • Rice Memorial Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology PA-Woodbury
    • Wyoming, Minnesota, United States, 55092
      • Fairview Lakes Medical Center
  • Missouri
    • Ballwin, Missouri, United States, 63011
      • Saint Louis Cancer and Breast Institute-Ballwin
    • Bolivar, Missouri, United States, 65613
      • Central Care Cancer Center - Bolivar
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Cape Girardeau, Missouri, United States, 63703
      • Southeast Cancer Center
    • Farmington, Missouri, United States, 63640
      • Parkland Health Center - Farmington
    • Jefferson City, Missouri, United States, 65109
      • Capital Region Southwest Campus
    • Joplin, Missouri, United States, 64804
      • Freeman Health System
    • Joplin, Missouri, United States, 64804
      • Mercy Hospital Joplin
    • Rolla, Missouri, United States, 65401
      • Delbert Day Cancer Institute at PCRMC
    • Rolla, Missouri, United States, 65401
      • Mercy Clinic-Rolla-Cancer and Hematology
    • Saint Joseph, Missouri, United States, 64506
      • Heartland Regional Medical Center
    • 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 Louis, Missouri, United States, 63128
      • Mercy Hospital South
    • Saint Louis, Missouri, United States, 63109
      • Saint Louis Cancer and Breast Institute-South City
    • Sainte Genevieve, Missouri, United States, 63670
      • Sainte Genevieve County Memorial Hospital
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
    • Sullivan, Missouri, United States, 63080
      • Missouri Baptist Sullivan Hospital
    • Sunset Hills, Missouri, United States, 63127
      • BJC Outpatient Center at Sunset Hills
    • Washington, Missouri, United States, 63090
      • Mercy Hospital Washington
  • Montana
    • Anaconda, Montana, United States, 59711
      • Community Hospital of Anaconda
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Benefis Healthcare- Sletten Cancer Institute
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Missoula, Montana, United States, 59804
      • Community Medical Hospital
    • Missoula, Montana, United States, 59802
      • Saint Patrick Hospital - Community Hospital
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • CHI Health Saint Francis
    • Kearney, Nebraska, United States, 68847
      • CHI Health Good Samaritan
    • Lincoln, Nebraska, United States, 68516
      • Southeast Nebraska Cancer Center - 68th Street Place
    • Lincoln, Nebraska, United States, 68510
      • Saint Elizabeth Regional Medical Center
    • Lincoln, Nebraska, United States, 68516
      • Cancer Partners of Nebraska - Pine Lake
    • 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
    • Papillion, Nebraska, United States, 68046
      • Midlands Community Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Women's Cancer Center of Nevada
  • New Jersey
    • Neptune, New Jersey, United States, 07753
      • Jersey Shore Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Cancer Center
    • Las Cruces, New Mexico, United States, 88011
      • Memorial Medical Center - Las Cruces
    • Rio Rancho, New Mexico, United States, 87124
      • Presbyterian Rust Medical Center/Jorgensen Cancer Center
  • New York
    • Bay Shore, New York, United States, 11706
      • Northwell Health Imbert Cancer Center
    • Brightwaters, New York, United States, 11718
      • Island Gynecologic Oncology
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Lake Success, New York, United States, 11042
      • Northwell Health/Center for Advanced Medicine
    • 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
    • Clinton, North Carolina, United States, 28328
      • Southeastern Medical Oncology Center-Clinton
    • Goldsboro, North Carolina, United States, 27534
      • Southeastern Medical Oncology Center-Goldsboro
    • Jacksonville, North Carolina, United States, 28546
      • Southeastern Medical Oncology Center-Jacksonville
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Health System - Akron Campus
    • Alliance, Ohio, United States, 44601
      • Aultman Alliance Community Hospital
    • Beachwood, Ohio, United States, 44122
      • UHHS-Chagrin Highlands Medical Center
    • Belpre, Ohio, United States, 45714
      • Strecker Cancer Center-Belpre
    • Canton, Ohio, United States, 44710
      • Aultman Health Foundation
    • Centerville, Ohio, United States, 45459
      • Miami Valley Hospital South
    • Chardon, Ohio, United States, 44024
      • Geauga Hospital
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional 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, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Cancer Center/Fairview Hospital
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • Columbus, Ohio, United States, 43219
      • The Mark H Zangmeister Center
    • Columbus, Ohio, United States, 43214
      • Columbus Oncology and Hematology Associates Inc
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital
    • Columbus, Ohio, United States, 43213
      • Mount Carmel East Hospital
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health Center West
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Delaware, Ohio, United States, 43015
      • Delaware Health Center-Grady Cancer Center
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Dublin, Ohio, United States, 43016
      • Dublin Methodist Hospital
    • Gahanna, Ohio, United States, 43230
      • Central Ohio Breast and Endocrine Surgery
    • Grove City, Ohio, United States, 43123
      • Mount Carmel Grove City Hospital
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Lima, Ohio, United States, 45801
      • Saint Rita's Medical Center
    • Mansfield, Ohio, United States, 44903
      • OhioHealth Mansfield Hospital
    • Marietta, Ohio, United States, 45750
      • Marietta Memorial Hospital
    • Marion, Ohio, United States, 43302
      • OhioHealth Marion General Hospital
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Hospital Cancer Center
    • 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
    • Perrysburg, Ohio, United States, 43551
      • Mercy Health Perrysburg Cancer Center
    • Portsmouth, Ohio, United States, 45662
      • Southern Ohio Medical Center
    • Toledo, Ohio, United States, 43608
      • Saint Vincent Mercy Medical Center
    • Toledo, Ohio, United States, 43623
      • Mercy Health - Saint Anne 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
      • UH Seidman Cancer Center at Saint John Medical Center
    • Zanesville, Ohio, United States, 43701
      • Genesis Healthcare System Cancer Care Center
  • Oklahoma
    • Lawton, Oklahoma, United States, 73505
      • Cancer Centers of Southwest Oklahoma Research
    • 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 Medical 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
    • Newberg, Oregon, United States, 97132
      • Providence Newberg Medical Center
    • Ontario, Oregon, United States, 97914
      • Saint Alphonsus Medical Center-Ontario
    • 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
    • Redmond, Oregon, United States, 97756
      • Saint Charles Health System-Redmond
    • Tualatin, Oregon, United States, 97062
      • Legacy Meridian Park Hospital
  • Pennsylvania
    • Butler, Pennsylvania, United States, 16001
      • UPMC Hillman Cancer Center at Butler Health System
    • Erie, Pennsylvania, United States, 16505
      • UPMC Hillman Cancer Center Erie
    • Paoli, Pennsylvania, United States, 19301
      • Paoli Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19114
      • Jefferson Torresdale Hospital
    • Pittsburgh, Pennsylvania, United States, 15224
      • West Penn Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC-Magee Womens Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute (UPCI)
    • Pittsburgh, Pennsylvania, United States, 15237
      • UPMC-Passavant Hospital
    • Willow Grove, Pennsylvania, United States, 19090
      • Asplundh Cancer Pavilion
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women and Infants Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Greenville, South Carolina, United States, 29607
      • Saint Francis Cancer Center
    • Greenville, South Carolina, United States, 29601
      • Saint Francis Hospital
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Bristol Regional Medical Center
    • Kingsport, Tennessee, United States, 37660
      • Ballad Health Cancer Care - Kingsport
    • Kingsport, Tennessee, United States, 37660
      • Wellmont Holston Valley Hospital and Medical Center
    • Knoxville, Tennessee, United States, 37916
      • Thompson Cancer Survival Center
    • Knoxville, Tennessee, United States, 37932
      • Thompson Cancer Survival Center - West
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University/Ingram Cancer Center
    • Nashville, Tennessee, United States, 37204
      • Vanderbilt Breast Center at One Hundred Oaks
  • Texas
    • Bryan, Texas, United States, 77802
      • Saint Joseph Regional Cancer Center
    • Dallas, Texas, United States, 75235
      • Parkland Memorial Hospital
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Houston, Texas, United States, 77070
      • Methodist Willowbrook Hospital
    • Houston, Texas, United States, 77094
      • Houston Methodist West Hospital
    • Sugar Land, Texas, United States, 77479
      • Houston Methodist Sugar Land Hospital
    • The Woodlands, Texas, United States, 77385
      • Houston Methodist The Woodlands Hospital
  • Virginia
    • Bristol, Virginia, United States, 24201
      • Wellmont Medical Associates-Bristol
    • Norton, Virginia, United States, 24273
      • Southwest VA Regional Cancer Center
  • Washington
    • Aberdeen, Washington, United States, 98520
      • Providence Regional Cancer System-Aberdeen
    • Bellingham, Washington, United States, 98225
      • PeaceHealth Saint Joseph Medical Center
    • Bremerton, Washington, United States, 98310
      • Harrison 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, 98003
      • Saint Francis Hospital
    • Issaquah, Washington, United States, 98029
      • Swedish Cancer Institute-Issaquah
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • 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
    • Port Townsend, Washington, United States, 98368
      • Jefferson Healthcare
    • Seattle, Washington, United States, 98107
      • Swedish Medical Center-Ballard Campus
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center-First Hill
    • Seattle, Washington, United States, 98104
      • Pacific Gynecology Specialists
    • Seattle, Washington, United States, 98122-5711
      • Swedish Medical Center-Cherry Hill
    • Sedro-Woolley, Washington, United States, 98284
      • PeaceHealth United General Medical Center
    • Shelton, Washington, United States, 98584
      • Providence Regional Cancer System-Shelton
    • 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
    • Yelm, Washington, United States, 98597
      • Providence Regional Cancer System-Yelm
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • West Virginia University Charleston Division
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital Cancer Center Green Bay
    • Green Bay, Wisconsin, United States, 54303
      • Saint Vincent Hospital Cancer Center at Saint Mary's
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Mukwonago, Wisconsin, United States, 53149
      • ProHealth D N Greenwald Center
    • New Richmond, Wisconsin, United States, 54017
      • Cancer Center of Western Wisconsin
    • Oconomowoc, Wisconsin, United States, 53066
      • ProHealth Oconomowoc Memorial Hospital
    • Oconto Falls, Wisconsin, United States, 54154
      • Saint Vincent Hospital Cancer Center at Oconto Falls
    • Sturgeon Bay, Wisconsin, United States, 54235-1495
      • Saint Vincent Hospital Cancer Center at Sturgeon Bay
    • Waukesha, Wisconsin, United States, 53188
      • UW Cancer Center at ProHealth Care
    • Waukesha, Wisconsin, United States, 53188
      • ProHealth Waukesha Memorial Hospital
  • Wyoming
    • Cody, Wyoming, United States, 82414
      • Billings Clinic-Cody
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women with recurrent/persistent platinum-resistant ovarian, primary peritoneal, or fallopian tube cancers; platinum-resistant disease is defined as progression within < 6 months from completion of platinum based therapy. The date should be calculated from the last administered dose of platinum therapy
• Patients must have histologically or cytologically confirmed ovarian cancer, peritoneal cancer or fallopian tube cancer and must have a histological diagnosis of high grade serous, grade 3 endometrioid or clear cell carcinoma based on local histopathological findings. Patients with low grade serous, grade 1 or 2 endometrioid, mixed epithelial, undifferentiated carcinoma, or mucinous carcinoma histologies are also eligible, provided that the patient has a known deleterious BRCA1 or BRCA2 mutation identified through testing at a clinical laboratory. Histologic confirmation of the original primary tumor is required via the pathology report (upload of report required). Confirmation of BRCA1 and BRCA2 germline and/or somatic mutation status and hormone receptor (HR) status is required for all entered patients (if available) via testing report (upload of report[s] required)
• Evaluable disease - defined as RECIST 1.1 measurable disease OR non-measurable disease (defined as solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions OR ascites and/or pleural effusion that has been pathologically demonstrated to be disease-related in the setting of a CA125 >= 2 x upper limit of normal [ULN])

• Prior therapy:

  • At least two prior treatment regimens (including primary therapy) but up to 5 lines of systemic anticancer therapy. Hormonal therapy (such as tamoxifen, aromatase inhibitors) will not count as a previous treatment regimen.
  • Prior use of bevacizumab in the upfront or recurrent setting is required.
  • Prior use of PARP inhibitor is allowed.
  • Prior use of immune checkpoint blockade (e.g., a PD-L1/PD-1inhibitor or a CTLA-4 inhibitor) is allowed
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Hemoglobin > 10 g/dL
• Platelets >= 100,000/mcL
• Creatinine clearance (CrCL) or estimated glomerular filtration rate (eGFR) of > 50 mL/min estimated using either the Cockcroft-Gault equation, the Modification of Diet in Renal Disease Study, or as reported in the comprehensive metabolic panel/basic metabolic panel (eGFR)
• Urine protein: creatinine ratio (UPC) of =< 1
• Total serum bilirubin level =< 1.5 x ULN (patients with known Gilbert's disease who have bilirubin level =< 3 x ULN may be enrolled)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN
• Age >= 18 years
• Body weight > 30 kg
• Adequately controlled blood pressure (systolic blood pressure [SBP] =< 140; diastolic blood pressure [DBP] =< 90 mmHg) on a maximum of three antihypertensive medications. Patients must have a BP of =< 140/90 mmHg taken in the clinic setting by a medical professional within 2 weeks prior to study registration. It is strongly recommended that patients who are on three antihypertensive medications be followed by a cardiologist or a primary care physician for management of BP while on protocol. Patients must be willing and able to check and record daily blood pressure readings. BP cuffs will be provided to patients randomized to the cediranib-containing arms
• Adequately controlled thyroid dysfunction with no symptoms of thyroid dysfunction and normal thyroid stimulating hormone (TSH). If TSH is not within normal range despite no symptoms of thyroid dysfunction, normal free T4 level is required
• Able to swallow and retain oral medications and no gastrointestinal (GI) illnesses that would preclude absorption of olaparib and cediranib as judged by treating physician
• Toxicities of prior therapy (excepting alopecia and vitiligo), should be resolved to less than or equal to grade 1 as per Common Terminology Criteria for Adverse Events (CTCAE) v5.0

• Women of childbearing potential (WOCBP) must agree to use two forms of birth control (hormonal or barrier method of birth control; abstinence). Note: Definition of women of no longer having childbearing potential: Postmenopausal or evidence of non-childbearing status for women of childbearing potential as confirmed by a negative urine or serum pregnancy test within 7 days prior to start of study treatment. Postmenopausal is defined as: Age >= 60 years, or age < 60 with any one or more of the conditions below:

  • Amenorrhoeic for >= 1 year in the absence of chemotherapy and/or hormonal treatments,
  • Luteinizing hormone and/or follicle stimulating hormone and/or estradiol levels in the post-menopausal range,
  • Radiation-induced oophorectomy with last menses > 1 year ago,
  • Chemotherapy-induced menopause with > 1 year interval since last menses,
  • Surgical sterilization (bilateral oophorectomy or hysterectomy)
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and authorization permitting release of personal health information

Exclusion Criteria:

• Primary platinum-refractory disease defined as progression during first-line platinum-based chemotherapy
• Rising CA-125 only without RECIST 1.1 evaluable disease

• Prior therapy:

  • Patients who have had chemotherapy, investigational drugs or radiotherapy within 3 weeks prior to study registration or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier.
  • Patients may not have had hormonal therapy within 2 weeks of study registration. Patients receiving raloxifene for bone health as per Food and Drug Administration (FDA) indication may remain on raloxifene absent other drug interactions.
  • Prior use of concurrent olaparib and cediranib combination.
  • Patients who have experienced immune-mediated adverse events requiring dose modification or discontinuation.

  • For patients who have received prior PARP inhibitor:

    • Patients who have required dose modification or dose reduction of olaparib will not be eligible, as they will not be able to start this study at full dose.
    • Patients who have required dose reduction of non-olaparib PARP inhibitors for hematologic adverse events will not be eligible (Note: niraparib that is initiated at 200mg daily per weight and platelet guidelines is not considered a dose reduction).
    • Patients who required dose-reduction of non-olaparib PARP inhibitors for non-hematologic adverse events may be eligible after discussion with the Study Chair if the treating investigator feels that they could appropriately receive olaparib at full dose.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 3 months prior to study registration
• Current signs and/or symptoms of bowel obstruction or signs and/or symptoms of bowel obstruction within 3 months of study registration except temporary (< 24 hr) improved with medical management, within last 3 months
• Any prior grade >= 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE > grade 1
• Dependency on IV hydration or total parenteral nutrition (TPN)
• Pregnant women. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with these drugs, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Patients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) scans should not be included on this study, since neurologic dysfunction may confound the evaluation of neurologic and other adverse events. Patients with treated brain metastases and resolution of any associated symptoms must demonstrate stable post-therapeutic imaging for at least 6 months following therapy prior to starting study registration

• Patients who have the following clinical conditions are considered to be at increased risk for cardiac toxicities. Patients with any cardiac history of the following conditions:

  • History of myocardial infarction or myocarditis within six months of study registration
  • Unstable angina
  • Resting electrocardiogram (ECG) with clinically significant abnormal findings.
  • New York Heart Association functional classification of III or IV

• If cardiac function assessment is clinically indicated or performed: left ventricular ejection fraction (LVEF) less than normal per institutional guidelines, or < 55%, if threshold for normal not otherwise specified by institutional guidelines. Patients with the following risk factors should have a baseline cardiac function assessment:

  • Prior treatment with anthracyclines
  • Prior treatment with trastuzumab or T-DM1
  • Prior central thoracic radiation therapy (RT), including RT to the heart
  • History of myocardial infarction within 6 to 12 months (Patients with history of myocardial infarction within 6 months are excluded from the study)
  • Prior history of impaired cardiac function
• History of stroke or transient ischemic attack within six months of study registration
• Clinically significant peripheral vascular disease or vascular disease (aortic aneurysm or aortic dissection)
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study treatment. Patients must have recovered from any effects of any major surgery and surgical wound should have healed prior to starting treatment. Note: Local surgery of isolated lesions for palliative intent is acceptable
• Evidence of coagulopathy or bleeding diathesis. Therapeutic anticoagulation for prior thromboembolic events, including warfarin, is permitted. Patients receiving warfarin are recommended to have careful monitoring of international normalized ratio (INR)
• Evidence suggestive of myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) on peripheral blood smear or bone marrow biopsy, if clinically indicated. No prior allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUBCT)
• Human immunodeficiency virus (HIV) positive patients due to potential drug and drug interactions
• Patients may not use any complementary or alternative medicines including natural herbal products or folk remedies as they may interfere with the effectiveness of the study treatments
• Receipt of live attenuated vaccine within 30 days prior to the first dose of study treatment. Note: Patients, if enrolled, should not receive live vaccine whilst receiving study treatment and up to 30 days after the last dose of study treatment
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (other than atrial fibrillation with controlled ventricular rate), or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring adverse events or compromise the ability of the patient to given written informed consent
• Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4. Dihydropyridine calcium-channel blockers are permitted for management of hypertension

• Current or prior use of immunosuppressive medication within 14 days of study registration. The following are exceptions to this criterion:

  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to durvalumab, olaparib, or cediranib
• Patients with active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice), hepatitis B (known positive hepatitis B virus [HBV] surface antigen (HBsAg) result), or hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for hepatitis C virus (HCV) ribonucleic acid (RNA)
• Patients who have a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I (paclitaxel, doxorubicin, topotecan hydrochloride)); Patients receive paclitaxel IV over 60 minutes on days 1, 8, and 15, or pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8 and 15 or days 1-5 per the discretion of the treating physician. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.	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; Procedure: Biospecimen Collection; Undergo collection of blood; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Drug: Paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat; Procedure: Computed Tomography; Undergo CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Drug: Topotecan Hydrochloride; Given IV; Other Names: Hycamtin; Hycamptamine; SKF S-104864-A; Topotecan HCl; topotecan hydrochloride (oral); Potactasol; Evotopin; Topotec; Procedure: Computed Tomography with Contrast; Undergo CT with contrast; Other Names: Contrast Enhanced Computed Tomography; CONTRAST ENHANCED CT SCAN; Contrast-enhanced Computed Tomography; CT Scan With Contrast; CT with Contrast; Procedure: Echocardiography; Undergo ECHO; Other Names: EC; Procedure: Multigated Acquisition Scan; Undergo MUGA; Other Names: Blood Pool Scan; Equilibrium Radionuclide Angiography; Gated Blood Pool Imaging; MUGA; Radionuclide Ventriculography; RNVG; SYMA Scanning; Synchronized Multigated Acquisition Scanning; MUGA Scan; Multi-Gated Acquisition Scan; Radionuclide Ventriculogram Scan; Gated Heart Pool Scan
Experimental: Arm II (durvalumab, cediranib maleate, olaparib); Patients receive durvalumab IV over 60 minutes on day 1, cediranib maleate PO QD Monday through Friday, and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.	Procedure: Biospecimen Collection; Undergo collection of blood; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Computed Tomography; Undergo CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Biological: Durvalumab; Given IV; Other Names: Imfinzi; Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer; MEDI-4736; MEDI4736; Drug: Olaparib; Given PO; Other Names: Lynparza; AZD 2281; AZD-2281; AZD2281; KU-0059436; PARP Inhibitor AZD2281; Olanib; Olaparix; Procedure: Computed Tomography with Contrast; Undergo CT with contrast; Other Names: Contrast Enhanced Computed Tomography; CONTRAST ENHANCED CT SCAN; Contrast-enhanced Computed Tomography; CT Scan With Contrast; CT with Contrast; Drug: Cediranib Maleate; Given PO; Other Names: AZD2171; AZD2171 Maleate; Recentin; Procedure: Echocardiography; Undergo ECHO; Other Names: EC; Procedure: Multigated Acquisition Scan; Undergo MUGA; Other Names: Blood Pool Scan; Equilibrium Radionuclide Angiography; Gated Blood Pool Imaging; MUGA; Radionuclide Ventriculography; RNVG; SYMA Scanning; Synchronized Multigated Acquisition Scanning; MUGA Scan; Multi-Gated Acquisition Scan; Radionuclide Ventriculogram Scan; Gated Heart Pool Scan
Experimental: Arm III (durvalumab, cediranib maleate); Patients receive durvalumab IV over 60 minutes on day 1 and cediranib maleate PO QD Monday through Friday. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.	Procedure: Biospecimen Collection; Undergo collection of blood; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Computed Tomography; Undergo CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Biological: Durvalumab; Given IV; Other Names: Imfinzi; Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer; MEDI-4736; MEDI4736; Procedure: Computed Tomography with Contrast; Undergo CT with contrast; Other Names: Contrast Enhanced Computed Tomography; CONTRAST ENHANCED CT SCAN; Contrast-enhanced Computed Tomography; CT Scan With Contrast; CT with Contrast; Drug: Cediranib Maleate; Given PO; Other Names: AZD2171; AZD2171 Maleate; Recentin; Procedure: Echocardiography; Undergo ECHO; Other Names: EC; Procedure: Multigated Acquisition Scan; Undergo MUGA; Other Names: Blood Pool Scan; Equilibrium Radionuclide Angiography; Gated Blood Pool Imaging; MUGA; Radionuclide Ventriculography; RNVG; SYMA Scanning; Synchronized Multigated Acquisition Scanning; MUGA Scan; Multi-Gated Acquisition Scan; Radionuclide Ventriculogram Scan; Gated Heart Pool Scan
Experimental: Arm IV (cediranib maleate, olaparib); Patients receive cediranib maleate PO QD on days 1-28 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.	Procedure: Biospecimen Collection; Undergo collection of blood; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Computed Tomography; Undergo CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Drug: Olaparib; Given PO; Other Names: Lynparza; AZD 2281; AZD-2281; AZD2281; KU-0059436; PARP Inhibitor AZD2281; Olanib; Olaparix; Procedure: Computed Tomography with Contrast; Undergo CT with contrast; Other Names: Contrast Enhanced Computed Tomography; CONTRAST ENHANCED CT SCAN; Contrast-enhanced Computed Tomography; CT Scan With Contrast; CT with Contrast; Drug: Cediranib Maleate; Given PO; Other Names: AZD2171; AZD2171 Maleate; Recentin; Procedure: Echocardiography; Undergo ECHO; Other Names: EC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Will be presented by Kaplan Meier methods.	From study entry to time of progression or death, whichever occurs first, assessed up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	Quantified as the binomial proportion of patients with measurable disease at enrollment who have a best overall response of complete response (CR) or partial response (PR).	From the start of the treatment until disease progression/recurrence, assessed up to 5 years
Duration of response	Will be presented by Kaplan Meier methods.	From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 5 years
Overall survival	Will be presented by Kaplan Meier methods.	Time from study entry to date of death from any cause, assessed up to 5 years
Incidence of adverse events	All adverse events, including severe adverse events and treatment-related adverse events, will be categorized and graded for severity according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.	Up to 30 days post treatment

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: NRG Oncology
• Investigators: Principal Investigator: Jung-min Lee, NRG Oncology

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2021
• Primary Completion (Actual): January 26, 2023
• Study Completion (Estimated): January 8, 2025

Study Registration Dates

• First Submitted: February 4, 2021
• First Submitted That Met QC Criteria: February 4, 2021
• First Posted (Actual): February 5, 2021

Study Record Updates

• Last Update Posted (Estimated): January 11, 2024
• Last Update Submitted That Met QC Criteria: January 10, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Endocrine System Diseases; Disease Attributes; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Neoplasms, Cystic, Mucinous, and Serous; Endometrial Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Carcinoma; Recurrence; Adenocarcinoma; Ovarian Neoplasms; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial; Cystadenocarcinoma, Serous; Carcinoma, Endometrioid; Cystadenocarcinoma; Adenocarcinoma, Clear Cell; Carcinoma, Transitional Cell; Adenocarcinoma, Mucinous; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Poly(ADP-ribose) Polymerase Inhibitors; Antibiotics, Antineoplastic; Topoisomerase I Inhibitors; Paclitaxel; Olaparib; Immunoglobulins; Durvalumab; Albumin-Bound Paclitaxel; Doxorubicin; Liposomal doxorubicin; Antibodies, Monoclonal; Maleic acid; Topotecan; Immunoglobulin G; Cediranib
• Other Study ID Numbers: NCI-2021-00615 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180868 (U.S. NIH Grant/Contract); NRG-GY023 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No