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Testování kombinace Cediranibu a Olaparibu ve srovnání s každým lékem samotným nebo jinou chemoterapií u recidivujícího karcinomu vaječníků rezistentního na platinu

30. září 2026 aktualizováno: National Cancer Institute (NCI)

Randomizovaná studie fáze II/III kombinace cediranibu a olaparibu ve srovnání s cediranibem nebo olaparibem samotným nebo standardní chemoterapií u žen s recidivující platinou rezistentní nebo refrakterní rakovinou vaječníků, vejcovodů nebo primárním karcinomem peritonea (COCOS)

This randomized phase II/III trial studies how well cediranib maleate and olaparib work when given together or separately, and compares them to standard chemotherapy in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has returned (recurrent) after receiving chemotherapy with drugs that contain platinum (platinum-resistant) or continued to grow while being treated with platinum-based chemotherapy drugs (platinum-refractory). Cediranib maleate and olaparib may stop the growth of tumor cells by blocking enzymes needed for cell growth. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving cediranib maleate and olaparib together may cause more damage to cancer cells when compared to either drug alone or standard chemotherapy.

Přehled studie

Postavení

Aktivní, ne nábor

Podmínky

Intervence / Léčba

Detailní popis

PRIMARY OBJECTIVES:

I. To assess the efficacy and identify (in)active arm(s) of the combination of cediranib maleate (cediranib) and olaparib, cediranib alone, olaparib alone, and physician's choice standard of care chemotherapy, as measured by progression-free survival (PFS) in the setting of recurrent platinum-resistant or-refractory ovarian, primary peritoneal or fallopian tube cancer. (Phase II) II. To assess the efficacy of the combination of cediranib and olaparib, and cediranib monotherapy, as measured by overall survival (OS) and PFS, as compared to physician's choice standard of care chemotherapy in women with recurrent platinum-resistant or-refractory ovarian, primary peritoneal or fallopian tube cancer. (Phase III)

SECONDARY OBJECTIVES:

I. To assess the efficacy of the combination of cediranib and olaparib, cediranib alone, olaparib alone, and physician's choice standard of care chemotherapy, as measured by objective response rate (ORR: partial or complete response) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, in the setting of recurrent platinum-resistant or-refractory ovarian, primary peritoneal or fallopian tube cancer. (Phase II) II. To assess safety endpoints, as measured by frequency and severity of adverse events by Common Terminology Criteria for Adverse Events (CTCAE). (Phase II and Phase III) III. To assess the efficacy of the combination of cediranib and olaparib, and cediranib monotherapy, as measured by ORR as compared to physician's choice standard of care chemotherapy in the setting of recurrent platinum-resistant or-refractory ovarian, primary peritoneal or fallopian tube cancer. (Phase III)

OBJECTIVES WITH INTEGRATED BIOMARKERS:

I. To assess correlation of homologous recombination deficiency (HRD) status, as assessed via BROCA-HR assay with response, as measured by PFS and ORR. (Phase II) II. To evaluate the prognostic and predictive role of circulating endothelial cells (CEC) on comparative effectiveness of targeted therapies and reference chemotherapy. (Phase II) III. To evaluate quality of life data compliance, as measured by the 9-item Disease Related Symptoms (DRS-9) subscale of the National Comprehensive Cancer Network (NCCN)-Functional Assessment of Cancer Therapy (FACT) Ovarian Symptom Index (NFOSI) for utilization and analysis in the Phase III study. (Phase II) IV. To assess correlation of HRD status, as assessed via BROCA-HR assay with response, as measured by OS, PFS and ORR. (Phase III) V. To evaluate the prognostic and predictive role of circulating endothelial cells (CEC) on comparative effectiveness of targeted therapies and reference chemotherapy. (Phase III) VI. To assess the effect on disease-related symptoms (DRS) as measured by the 9-item DRS-P subscale of the NCCN-FACT Ovarian Symptom Index-18 (NFOSI-18), of single agent cediranib and cediranib/olaparib combination, compared to standard chemotherapy, in the setting of recurrent platinum-resistant or-refractory ovarian, primary peritoneal or fallopian tube cancer. (Phase III)

EXPLORATORY OBJECTIVES:

I. To assess exploratory biomarkers of potential HRD, including genomic scarring, BRCA1 methylation, BRCA1 protein expression, and mutations in NHEJ, and other genes that might modify HRD. (Phase II and Phase III) II. To evaluate the prognostic and predictive role of angiogenic biomarkers, as assessed by the Duke plasma angiome. (Phase II and Phase III) III. To assess the effect on secondary measures of quality of life, as assessed by the treatment side effects (TSE) and function/well-being (F/WB) subscales of the NFOSI-18, sensory neuropathy as measured by the FACT/GOG-Ntx-4, and health utility as measured by the EQ-5D, of single agent cediranib and cediranib/olaparib combination, compared to standard chemotherapy, in the setting of recurrent platinum-resistant or-refractory ovarian, primary peritoneal or fallopian tube cancer. (Phase III)

OUTLINE:

PHASE II: Patients are randomized to 1 of 4 treatment arms.

ARM I (REFERENCE REGIMEN): Patients undergo physician's choice of standard of care chemotherapy, comprising either paclitaxel intravenously (IV) over 60 minutes on days 1, 8, 15, and 22 every 28 days (Regimen I); pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1 every 28 days (Regimen II); or topotecan hydrochloride IV over 30 minutes on days 1, 8, and 15 every 28 days or days 1-5 every 21 days (Regimen III). Treatment continues in the absence of disease progression or unacceptable toxicity. No modification of the assigned regimens, such as additional drugs (gemcitabine, or bevacizumab) is allowed. Patients also undergo computed tomography (CT) and magnetic resonance imaging (MRI) throughout the study. (12/05/2016)

ARM II (CEDIRANIB MALEATE AND OLAPARIB): Patients receive cediranib maleate orally (PO) once daily (QD) and olaparib PO twice daily (BID). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout the study.

ARM III (CEDIRANIB): Patients receive cediranib maleate PO daily continuously. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout the study.

ARM IV (OLAPARIB): Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout the study. (In July 2018, the Data Monitoring Committee voted to exclude the olaparib alone regimen).

PHASE III: Patients are randomized to 1 of 3 treatment arms.

ARM I (REFERENCE REGIMEN): Patients undergo physician's choice standard of care chemotherapy as in Phase II Arm I. No modification of the assigned regimens, such as additional drugs (gemcitabine or bevacizumab) is allowed. Patients also undergo CT and MRI throughout the study. (12/05/2016)

ARM II (CEDIRANIB AND OLAPARIB): Patients receive cediranib maleate PO and olaparib PO as in Phase II Arm II. Patients also undergo CT and MRI throughout the study.

ARM III (SINGLE AGENT): Patients receive cediranib maleate PO as determined by the Phase II study. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout the study.

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

Typ studie

Intervenční

Zápis (Aktuální)

582

Fáze

Fáze 2
Fáze 3

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

Japonsko
- - Osaka, Japonsko, 589 8511
    - Kindai University
  - Saitama, Japonsko, 350-1298
    - Saitama Medical University International Medical Center
  - Tokyo, Japonsko, 104 0045
    - National Cancer Center Hospital
- Ehime
  - Tōon, Ehime, Japonsko, 791-0295
    - Ehime University Hospital
- Hokkaido
  - Sapporo, Hokkaido, Japonsko, 060-8648
    - Hokkaido University Hospital
- Kagoshima-ken
  - Kagoshima, Kagoshima-ken, Japonsko, 890-8760
    - Kagoshima City Hospital
- Tokyo
  - Koto-ku, Tokyo, Japonsko, 135-8550
    - The Cancer Institute Hospital Of JFCR
Jižní Korea
- - Incheon, Jižní Korea, 405-760
    - Gachon University Gil Hospital
  - Seoul, Jižní Korea, 05505
    - Asan Medical Center
  - Seoul, Jižní Korea, 06273
    - Gangnam Severance Hospital
  - Seoul, Jižní Korea, 134-727
    - Kyung Hee University Hospital at Gangdong
  - Seoul, Jižní Korea, 139-706
    - Korea Cancer Center Hospital
- Daegu
  - Dalseo-gu, Daegu, Jižní Korea, 42601
    - Keimyung University-Dongsan Medical Center
- Kyeonggi-do
  - Seongnam, Kyeonggi-do, Jižní Korea, 463-707
    - Seoul National University Bundang Hospital
Kanada
- Alberta
  - Calgary, Alberta, Kanada, T2N 5G2
    - Arthur J E Child Comprehensive Cancer Centre
  - Edmonton, Alberta, Kanada, T6G 1Z2
    - Cross Cancer Institute
- Ontario
  - Barrie, Ontario, Kanada, L4M 6M2
    - Royal Victoria Regional Health Centre
  - Hamilton, Ontario, Kanada, L8V 5C2
    - Juravinski Cancer Centre at Hamilton Health Sciences
  - Kingston, Ontario, Kanada, K7L 2V7
    - Kingston Health Sciences Centre
  - London, Ontario, Kanada, N6A 4L6
    - London Regional Cancer Program
  - Sault Ste. Marie, Ontario, Kanada, P6B 0A8
    - Algoma District Cancer Program Sault Area Hospital
  - Toronto, Ontario, Kanada, M5G 2M9
    - University Health Network-Princess Margaret Hospital
  - Toronto, Ontario, Kanada, M4N 3M5
    - Odette Cancer Centre- Sunnybrook Health Sciences Centre
- Quebec
  - Montreal, Quebec, Kanada, H3T 1E2
    - Jewish General Hospital
  - Montreal, Quebec, Kanada, H2X 3E4
    - CHUM - Centre Hospitalier de l'Universite de Montreal
  - Montreal, Quebec, Kanada, H1T 2M4
    - CIUSSSEMTL-Hopital Maisonneuve-Rosemont
  - Québec, Quebec, Kanada, G1R 2J6
    - CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
Portoriko
- - San Juan, Portoriko, 00927
    - Centro Comprensivo de Cancer de UPR
Spojené státy
- Alabama
  - Birmingham, Alabama, Spojené státy, 35233
    - University of Alabama at Birmingham Cancer Center
- Alaska
  - Anchorage, Alaska, Spojené státy, 99508
    - Alaska Women's Cancer Care
  - Anchorage, Alaska, Spojené státy, 99508
    - Providence Alaska Medical Center
- Arkansas
  - Little Rock, Arkansas, Spojené státy, 72205
    - University of Arkansas for Medical Sciences
- California
  - Auburn, California, Spojené státy, 95602
    - Sutter Auburn Faith Hospital
  - Berkeley, California, Spojené státy, 94704
    - Alta Bates Summit Medical Center-Herrick Campus
  - Carmichael, California, Spojené státy, 95608
    - Mercy San Juan Medical Center
  - Elk Grove, California, Spojené státy, 95758
    - Mercy Cancer Center - Elk Grove
  - Greenbrae, California, Spojené státy, 94904
    - Marin Cancer Care Inc
  - La Jolla, California, Spojené státy, 92093
    - UC San Diego Moores Cancer Center
  - Mountain View, California, Spojené státy, 94040
    - Palo Alto Medical Foundation-Camino Division
  - Mountain View, California, Spojené státy, 94040
    - Palo Alto Medical Foundation-Gynecologic Oncology
  - Oakland, California, Spojené státy, 94611
    - Kaiser Permanente-Oakland
  - Palo Alto, California, Spojené státy, 94301
    - Palo Alto Medical Foundation Health Care
  - Rocklin, California, Spojené státy, 95765
    - Mercy Cancer Center - Rocklin
  - Roseville, California, Spojené státy, 95661
    - Sutter Roseville Medical Center
  - Sacramento, California, Spojené státy, 95816
    - Sutter Medical Center Sacramento
  - Sacramento, California, Spojené státy, 95817
    - University of California Davis Comprehensive Cancer Center
  - Sacramento, California, Spojené státy, 95814
    - Kaiser Permanente Downtown Commons
  - Sacramento, California, Spojené státy, 95825
    - Kaiser Permanente Sacramento Medical Center
  - Sacramento, California, Spojené státy, 95816
    - Mercy Cancer Center - Sacramento
  - San Francisco, California, Spojené státy, 94115
    - Kaiser Permanente-San Francisco
  - San Francisco, California, Spojené státy, 94158
    - UCSF Medical Center-Mission Bay
  - San Francisco, California, Spojené státy, 94115
    - California Pacific Medical Center-Pacific Campus
  - San Luis Obispo, California, Spojené státy, 93401
    - Pacific Central Coast Health Center-San Luis Obispo
  - Santa Clara, California, Spojené státy, 95051
    - Kaiser Permanente Medical Center - Santa Clara
  - Santa Cruz, California, Spojené státy, 95065
    - Palo Alto Medical Foundation-Santa Cruz
  - Santa Rosa, California, Spojené státy, 95403
    - Sutter Pacific Medical Foundation
  - Sunnyvale, California, Spojené státy, 94086
    - Palo Alto Medical Foundation-Sunnyvale
  - Vallejo, California, Spojené státy, 94589
    - Kaiser Permanente-Vallejo
  - Walnut Creek, California, Spojené státy, 94596
    - Kaiser Permanente-Walnut Creek
  - Woodland, California, Spojené státy, 95695
    - Woodland Memorial Hospital
- Colorado
  - Aurora, Colorado, Spojené státy, 80045
    - UCHealth University of Colorado Hospital
  - Colorado Springs, Colorado, Spojené státy, 80907
    - Penrose-Saint Francis Healthcare
  - Colorado Springs, Colorado, Spojené státy, 80909
    - UCHealth Memorial Hospital Central
  - Denver, Colorado, Spojené státy, 80205
    - Kaiser Permanente-Franklin
  - Denver, Colorado, Spojené státy, 80220
    - Rocky Mountain Cancer Centers-Rose
  - Fort Collins, Colorado, Spojené státy, 80524
    - Poudre Valley Hospital
  - Highlands Ranch, Colorado, Spojené státy, 80129
    - UCHealth Highlands Ranch Hospital
  - Lafayette, Colorado, Spojené státy, 80026
    - Kaiser Permanente-Rock Creek
  - Lone Tree, Colorado, Spojené státy, 80124
    - Kaiser Permanente-Lone Tree
- Connecticut
  - Danbury, Connecticut, Spojené státy, 06810
    - Danbury Hospital
  - Fairfield, Connecticut, Spojené státy, 06824
    - Smilow Cancer Hospital Care Center-Fairfield
  - Hartford, Connecticut, Spojené státy, 06105
    - Smilow Cancer Hospital Care Center at Saint Francis
  - Hartford, Connecticut, Spojené státy, 06102
    - Hartford Hospital
  - Middletown, Connecticut, Spojené státy, 06457
    - Middlesex Hospital
  - New Britain, Connecticut, Spojené státy, 06050
    - The Hospital of Central Connecticut
  - New Haven, Connecticut, Spojené státy, 06520
    - Yale University
  - Norwalk, Connecticut, Spojené státy, 06856
    - Norwalk Hospital
  - Trumbull, Connecticut, Spojené státy, 06611
    - Smilow Cancer Hospital Care Center-Trumbull
- Delaware
  - Newark, Delaware, Spojené státy, 19713
    - Helen F Graham Cancer Center
  - Newark, Delaware, Spojené státy, 19713
    - Medical Oncology Hematology Consultants PA
  - Newark, Delaware, Spojené státy, 19718
    - Christiana Care Health System-Christiana Hospital
- District of Columbia
  - Washington D.C., District of Columbia, Spojené státy, 20016
    - Sibley Memorial Hospital
- Florida
  - Gainesville, Florida, Spojené státy, 32610
    - UF Health Cancer Institute - Gainesville
  - Miami Beach, Florida, Spojené státy, 33140
    - Mount Sinai Medical Center
  - Orlando, Florida, Spojené státy, 32806
    - Orlando Health Cancer Institute
  - Sarasota, Florida, Spojené státy, 34239
    - Sarasota Memorial Hospital
- Georgia
  - Atlanta, Georgia, Spojené státy, 30308
    - Emory University Hospital Midtown
  - Atlanta, Georgia, Spojené státy, 30322
    - Emory University Hospital/Winship Cancer Institute
  - Atlanta, Georgia, Spojené státy, 30309
    - Piedmont Hospital
  - Atlanta, Georgia, Spojené státy, 30342
    - Northside Hospital
  - Augusta, Georgia, Spojené státy, 30912
    - Augusta University Medical Center
  - Austell, Georgia, Spojené státy, 30106
    - WellStar Cobb Hospital
  - Marietta, Georgia, Spojené státy, 30060
    - Wellstar Kennestone Hospital
  - Marietta, Georgia, Spojené státy, 30060
    - WellStar Health System Inc
  - Roswell, Georgia, Spojené státy, 30076
    - WellStar North Fulton Hospital
  - Savannah, Georgia, Spojené státy, 31405
    - Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
  - Savannah, Georgia, Spojené státy, 31404
    - Memorial Health University Medical Center
  - Smyrna, Georgia, Spojené státy, 30080
    - WellStar Vinings Health Park
- Hawaii
  - Honolulu, Hawaii, Spojené státy, 96813
    - Queen's Medical Center
  - Honolulu, Hawaii, Spojené státy, 96826
    - Kapiolani Medical Center for Women and Children
- Idaho
  - Boise, Idaho, Spojené státy, 83706
    - Saint Alphonsus Cancer Care Center-Boise
  - Boise, Idaho, Spojené státy, 83712
    - Saint Luke's Cancer Institute - Boise
  - Fruitland, Idaho, Spojené státy, 83619
    - Saint Luke's Cancer Institute - Fruitland
  - Meridian, Idaho, Spojené státy, 83642
    - Saint Luke's Cancer Institute - Meridian
  - Nampa, Idaho, Spojené státy, 83687
    - Saint Luke's Cancer Institute - Nampa
- Illinois
  - Aurora, Illinois, Spojené státy, 60504
    - Rush-Copley Medical Center
  - Bloomington, Illinois, Spojené státy, 61704
    - Illinois CancerCare-Bloomington
  - Canton, Illinois, Spojené státy, 61520
    - Illinois CancerCare-Canton
  - Carthage, Illinois, Spojené státy, 62321
    - Illinois CancerCare-Carthage
  - Centralia, Illinois, Spojené státy, 62801
    - Centralia Oncology Clinic
  - Chicago, Illinois, Spojené státy, 60611
    - Northwestern University
  - Chicago, Illinois, Spojené státy, 60612
    - John H Stroger Jr Hospital of Cook County
  - Chicago, Illinois, Spojené státy, 60657
    - UChicago Medicine Comprehensive Cancer Center - Saint Joseph Hospital
  - Chicago, Illinois, Spojené státy, 60612
    - Rush MD Anderson Cancer Center
  - Decatur, Illinois, Spojené státy, 62526
    - Decatur Memorial Hospital
  - Decatur, Illinois, Spojené státy, 62526
    - Cancer Care Specialists of Illinois - Decatur
  - Effingham, Illinois, Spojené státy, 62401
    - Crossroads Cancer Center
  - Eureka, Illinois, Spojené státy, 61530
    - Illinois CancerCare-Eureka
  - Evanston, Illinois, Spojené státy, 60201
    - NorthShore University HealthSystem-Evanston Hospital
  - Galesburg, Illinois, Spojené státy, 61401
    - Illinois CancerCare-Galesburg
  - Geneva, Illinois, Spojené státy, 60134
    - Northwestern Medicine Cancer Center Delnor
  - Glenview, Illinois, Spojené státy, 60026
    - NorthShore University HealthSystem-Glenbrook Hospital
  - Highland Park, Illinois, Spojené státy, 60035
    - NorthShore University HealthSystem-Highland Park Hospital
  - Hinsdale, Illinois, Spojené státy, 60521
    - Sudarshan K Sharma MD Limited-Gynecologic Oncology
  - Kewanee, Illinois, Spojené státy, 61443
    - Illinois CancerCare-Kewanee Clinic
  - Macomb, Illinois, Spojené státy, 61455
    - Illinois CancerCare-Macomb
  - O'Fallon, Illinois, Spojené státy, 62269
    - Cancer Care Center of O'Fallon
  - Ottawa, Illinois, Spojené státy, 61350
    - Illinois CancerCare-Ottawa Clinic
  - Pekin, Illinois, Spojené státy, 61554
    - Illinois CancerCare-Pekin
  - Peoria, Illinois, Spojené státy, 61615
    - Illinois CancerCare-Peoria
  - Peru, Illinois, Spojené státy, 61354
    - Illinois CancerCare-Peru
  - Princeton, Illinois, Spojené státy, 61356
    - Illinois CancerCare-Princeton
  - Springfield, Illinois, Spojené státy, 62702
    - Springfield Clinic
  - Springfield, Illinois, Spojené státy, 62781
    - Springfield Memorial Hospital
  - Warrenville, Illinois, Spojené státy, 60555
    - Northwestern Medicine Cancer Center Warrenville
  - Zion, Illinois, Spojené státy, 60099
    - Midwestern Regional Medical Center
- Indiana
  - Fort Wayne, Indiana, Spojené státy, 46845
    - Parkview Regional Medical Center
  - Indianapolis, Indiana, Spojené státy, 46202
    - Indiana University/Melvin and Bren Simon Cancer Center
  - Indianapolis, Indiana, Spojené státy, 46260
    - Ascension Saint Vincent Indianapolis Hospital
  - Richmond, Indiana, Spojené státy, 47374
    - Reid Health
  - South Bend, Indiana, Spojené státy, 46601
    - Memorial Hospital of South Bend
- Iowa
  - Clive, Iowa, Spojené státy, 50325
    - Mercy Cancer Center-West Lakes
  - Clive, Iowa, Spojené státy, 50325
    - UI Health Care Mission Cancer and Blood - West Des Moines Clinic
  - Des Moines, Iowa, Spojené státy, 50309
    - Iowa Methodist Medical Center
  - Des Moines, Iowa, Spojené státy, 50314
    - Mercy Medical Center - Des Moines
  - Des Moines, Iowa, Spojené státy, 50309
    - UI Health Care Mission Cancer and Blood - Des Moines Clinic
  - Des Moines, Iowa, Spojené státy, 50314
    - UI Health Care Mission Cancer and Blood - Laurel Clinic
  - Iowa City, Iowa, Spojené státy, 52242
    - University of Iowa/Holden Comprehensive Cancer Center
  - Sioux City, Iowa, Spojené státy, 51101
    - Siouxland Regional Cancer Center
  - West Des Moines, Iowa, Spojené státy, 50266
    - Mercy Medical Center-West Lakes
- Kansas
  - Wichita, Kansas, Spojené státy, 67214
    - Ascension Via Christi Hospitals Wichita
  - Wichita, Kansas, Spojené státy, 67208
    - Associates In Womens Health
- Kentucky
  - Edgewood, Kentucky, Spojené státy, 41017
    - Saint Elizabeth Healthcare Edgewood
  - Lexington, Kentucky, Spojené státy, 40536
    - University of Kentucky/Markey Cancer Center
- Louisiana
  - Baton Rouge, Louisiana, Spojené státy, 70809
    - Mary Bird Perkins Cancer Center
  - Baton Rouge, Louisiana, Spojené státy, 70809
    - Hematology/Oncology Clinic PLLC
  - Baton Rouge, Louisiana, Spojené státy, 70817
    - Woman's Hospital
  - Covington, Louisiana, Spojené státy, 70433
    - Women's Cancer Care-Covington
  - New Orleans, Louisiana, Spojené státy, 70121
    - Ochsner Medical Center Jefferson
- Maine
  - Bangor, Maine, Spojené státy, 04401
    - Eastern Maine Medical Center
  - Brewer, Maine, Spojené státy, 04412
    - Lafayette Family Cancer Center-EMMC
  - Scarborough, Maine, Spojené státy, 04074
    - MaineHealth Maine Medical Center- Scarborough
- Maryland
  - Baltimore, Maryland, Spojené státy, 21237
    - MedStar Franklin Square Medical Center/Weinberg Cancer Institute
  - Baltimore, Maryland, Spojené státy, 21287
    - Johns Hopkins University/Sidney Kimmel Cancer Center
  - Baltimore, Maryland, Spojené státy, 21204
    - Greater Baltimore Medical Center
  - Bel Air, Maryland, Spojené státy, 21014
    - UM Upper Chesapeake Medical Center
  - Bethesda, Maryland, Spojené státy, 20892
    - National Institutes of Health Clinical Center
  - Ocean Pines, Maryland, Spojené státy, 21811
    - TidalHealth Richard A Henson Cancer Institute
  - Salisbury, Maryland, Spojené státy, 21801
    - TidalHealth Peninsula Regional
- Massachusetts
  - Boston, Massachusetts, Spojené státy, 02215
    - Dana-Farber Cancer Institute
  - Boston, Massachusetts, Spojené státy, 02115
    - Brigham and Women's Hospital
  - Worcester, Massachusetts, Spojené státy, 01605
    - UMass Memorial Medical Center - Memorial Division
- Michigan
  - Ann Arbor, Michigan, Spojené státy, 48109
    - University of Michigan Rogel Cancer Center
  - Ann Arbor, Michigan, Spojené státy, 48106
    - Trinity Health Saint Joseph Mercy Hospital Ann Arbor
  - Brownstown, Michigan, Spojené státy, 48183
    - Henry Ford Cancer Institute-Downriver
  - Clinton Township, Michigan, Spojené státy, 48038
    - Henry Ford Macomb Hospital-Clinton Township
  - Detroit, Michigan, Spojené státy, 48202
    - Henry Ford Hospital
  - Detroit, Michigan, Spojené státy, 48201
    - Wayne State University/Karmanos Cancer Institute
  - Escanaba, Michigan, Spojené státy, 49829
    - OSF Saint Francis Hospital and Medical Group
  - Farmington Hills, Michigan, Spojené státy, 48334
    - Weisberg Cancer Treatment Center
  - Grand Rapids, Michigan, Spojené státy, 49503
    - Corewell Health Grand Rapids Hospitals - Butterworth Hospital
  - Kalamazoo, Michigan, Spojené státy, 49007
    - West Michigan Cancer Center
  - Lansing, Michigan, Spojené státy, 48912
    - University of Michigan Health - Sparrow Lansing
  - Pontiac, Michigan, Spojené státy, 48341
    - Trinity Health Saint Joseph Mercy Oakland Hospital
  - Traverse City, Michigan, Spojené státy, 49684
    - Munson Medical Center
  - West Bloomfield, Michigan, Spojené státy, 48322
    - Henry Ford West Bloomfield Hospital
- Minnesota
  - Bemidji, Minnesota, Spojené státy, 56601
    - Sanford Joe Lueken Cancer Center
  - Burnsville, Minnesota, Spojené státy, 55337
    - Fairview Ridges Hospital
  - Coon Rapids, Minnesota, Spojené státy, 55433
    - Mercy Hospital
  - Edina, Minnesota, Spojené státy, 55435
    - Fairview Southdale Hospital
  - Mankato, Minnesota, Spojené státy, 56001
    - Mayo Clinic Health Systems-Mankato
  - Maple Grove, Minnesota, Spojené státy, 55369
    - Fairview Clinics and Surgery Center Maple Grove
  - Maplewood, Minnesota, Spojené státy, 55109
    - Saint John's Hospital - Healtheast
  - Minneapolis, Minnesota, Spojené státy, 55407
    - Abbott-Northwestern Hospital
  - Minneapolis, Minnesota, Spojené státy, 55455
    - University of Minnesota/Masonic Cancer Center
  - Rochester, Minnesota, Spojené státy, 55905
    - Mayo Clinic in Rochester
  - Saint Louis Park, Minnesota, Spojené státy, 55416
    - Park Nicollet Clinic - Saint Louis Park
  - Saint Paul, Minnesota, Spojené státy, 55101
    - Regions Hospital
  - Saint Paul, Minnesota, Spojené státy, 55102
    - United Hospital
  - Shakopee, Minnesota, Spojené státy, 55379
    - Saint Francis Regional Medical Center
  - Woodbury, Minnesota, Spojené státy, 55125
    - Minnesota Oncology Hematology PA-Woodbury
- Mississippi
  - Jackson, Mississippi, Spojené státy, 39216
    - University of Mississippi Medical Center
- Missouri
  - Cape Girardeau, Missouri, Spojené státy, 63703
    - Saint Francis Medical Center
  - Columbia, Missouri, Spojené státy, 65212
    - MU Health - University Hospital/Ellis Fischel Cancer Center
  - Joplin, Missouri, Spojené státy, 64804
    - Mercy Hospital Joplin
  - Springfield, Missouri, Spojené státy, 65807
    - CoxHealth South Hospital
  - Springfield, Missouri, Spojené státy, 65804
    - Mercy Hospital Springfield
  - St Louis, Missouri, Spojené státy, 63110
    - Barnes-Jewish Hospital
  - St Louis, Missouri, Spojené státy, 63110
    - Washington University School of Medicine
- Montana
  - Billings, Montana, Spojené státy, 59101
    - Billings Clinic Cancer Center
  - Bozeman, Montana, Spojené státy, 59715
    - Bozeman Health Deaconess Hospital
  - Great Falls, Montana, Spojené státy, 59405
    - Benefis Sletten Cancer Institute
- Nebraska
  - Grand Island, Nebraska, Spojené státy, 68803
    - Nebraska Cancer Specialists/Oncology Hematology West PC
  - Kearney, Nebraska, Spojené státy, 68847
    - CHI Health Good Samaritan
  - Omaha, Nebraska, Spojené státy, 68114
    - Nebraska Methodist Hospital
  - Omaha, Nebraska, Spojené státy, 68124
    - Alegent Health Bergan Mercy Medical Center
  - Omaha, Nebraska, Spojené státy, 68130
    - Alegent Health Lakeside Hospital
- Nevada
  - Las Vegas, Nevada, Spojené státy, 89106
    - Women's Cancer Center of Nevada
- New Hampshire
  - Lebanon, New Hampshire, Spojené státy, 03756
    - Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
  - Nashua, New Hampshire, Spojené státy, 03063
    - Dartmouth Cancer Center - Nashua
- New Jersey
  - Camden, New Jersey, Spojené státy, 08103
    - Cooper Hospital University Medical Center
  - Hackensack, New Jersey, Spojené státy, 07601
    - Hackensack University Medical Center
  - Hamilton, New Jersey, Spojené státy, 08690
    - The Cancer Institute of New Jersey Hamilton
  - Morristown, New Jersey, Spojené státy, 07960
    - Morristown Medical Center
  - Neptune City, New Jersey, Spojené státy, 07753
    - Jersey Shore Medical Center
  - New Brunswick, New Jersey, Spojené státy, 08903
    - Rutgers Cancer Institute of New Jersey
  - Somerville, New Jersey, Spojené státy, 08876
    - Robert Wood Johnson University Hospital Somerset
  - Summit, New Jersey, Spojené státy, 07902
    - Overlook Hospital
  - Voorhees Township, New Jersey, Spojené státy, 08043
    - MD Anderson Cancer Center at Cooper-Voorhees
- New Mexico
  - Albuquerque, New Mexico, Spojené státy, 87106
    - Southwest Gynecologic Oncology Associates Inc
  - Albuquerque, New Mexico, Spojené státy, 87106
    - University of New Mexico Cancer Center
  - Las Cruces, New Mexico, Spojené státy, 88011
    - Memorial Medical Center-Las Cruces
- New York
  - Albany, New York, Spojené státy, 12208
    - Women's Cancer Care Associates LLC
  - Brooklyn, New York, Spojené státy, 11203
    - State University of New York Downstate Medical Center
  - Buffalo, New York, Spojené státy, 14263
    - Roswell Park Cancer Institute
  - New York, New York, Spojené státy, 10016
    - Laura and Isaac Perlmutter Cancer Center at NYU Langone
  - Rochester, New York, Spojené státy, 14642
    - University of Rochester
  - Stony Brook, New York, Spojené státy, 11794
    - Stony Brook University Medical Center
  - Syracuse, New York, Spojené státy, 13210
    - State University of New York Upstate Medical University
  - The Bronx, New York, Spojené státy, 10461
    - Montefiore Medical Center-Einstein Campus
  - White Plains, New York, Spojené státy, 10601
    - Dickstein Cancer Treatment Center
- North Carolina
  - Asheville, North Carolina, Spojené státy, 28803
    - AdventHealth Infusion Center Asheville
  - Chapel Hill, North Carolina, Spojené státy, 27599
    - UNC Lineberger Comprehensive Cancer Center
  - Clyde, North Carolina, Spojené státy, 28721
    - AdventHealth Infusion Center Haywood
  - Durham, North Carolina, Spojené státy, 27710
    - Duke University Medical Center
  - Goldsboro, North Carolina, Spojené státy, 27534
    - Southeastern Medical Oncology Center-Goldsboro
  - Hendersonville, North Carolina, Spojené státy, 28791
    - Margaret R Pardee Memorial Hospital
  - Hendersonville, North Carolina, Spojené státy, 28792
    - AdventHealth Hendersonville
  - Jacksonville, North Carolina, Spojené státy, 28546
    - Southeastern Medical Oncology Center-Jacksonville
  - Pinehurst, North Carolina, Spojené státy, 28374
    - FirstHealth of the Carolinas-Moore Regional Hospital
  - Raleigh, North Carolina, Spojené státy, 27609
    - Duke Cancer Center Raleigh
  - Wilmington, North Carolina, Spojené státy, 28401
    - Novant Health New Hanover Regional Medical Center
  - Winston-Salem, North Carolina, Spojené státy, 27157
    - Wake Forest University Health Sciences
- North Dakota
  - Bismarck, North Dakota, Spojené státy, 58501
    - Sanford Bismarck Medical Center
  - Fargo, North Dakota, Spojené státy, 58122
    - Sanford Roger Maris Cancer Center
  - Fargo, North Dakota, Spojené státy, 58122
    - Sanford Broadway Medical Center
- Ohio
  - Akron, Ohio, Spojené státy, 44307
    - Cleveland Clinic Akron General
  - Canton, Ohio, Spojené státy, 44710
    - Aultman Health Foundation
  - Centerville, Ohio, Spojené státy, 45459
    - Miami Valley Hospital South
  - Cincinnati, Ohio, Spojené státy, 45219
    - University of Cincinnati Cancer Center-UC Medical Center
  - Cincinnati, Ohio, Spojené státy, 45220
    - Good Samaritan Hospital - Cincinnati
  - Cincinnati, Ohio, Spojené státy, 45247
    - TriHealth Cancer Institute-Westside
  - Cleveland, Ohio, Spojené státy, 44109
    - MetroHealth Medical Center
  - Cleveland, Ohio, Spojené státy, 44195
    - Cleveland Clinic Foundation
  - Cleveland, Ohio, Spojené státy, 44111
    - Cleveland Clinic Cancer Center/Fairview Hospital
  - Columbus, Ohio, Spojené státy, 43214
    - Riverside Methodist Hospital
  - Columbus, Ohio, Spojené státy, 43210
    - Ohio State University Comprehensive Cancer Center
  - Columbus, Ohio, Spojené státy, 43219
    - The Mark H Zangmeister Center
  - Dayton, Ohio, Spojené státy, 45405
    - Grandview Hospital
  - Findlay, Ohio, Spojené státy, 45840
    - Orion Cancer Care
  - Mayfield Heights, Ohio, Spojené státy, 44124
    - Hillcrest Hospital Cancer Center
  - Sylvania, Ohio, Spojené státy, 43560
    - ProMedica Flower Hospital
  - Toledo, Ohio, Spojené státy, 43606
    - ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
  - West Chester, Ohio, Spojené státy, 45069
    - University of Cincinnati Cancer Center-West Chester
  - Wright-Patterson Air Force Base, Ohio, Spojené státy, 45433
    - Wright-Patterson Medical Center
- Oklahoma
  - Oklahoma City, Oklahoma, Spojené státy, 73104
    - University of Oklahoma Health Sciences Center
  - Tulsa, Oklahoma, Spojené státy, 74146
    - Oklahoma Cancer Specialists and Research Institute-Tulsa
  - Tulsa, Oklahoma, Spojené státy, 74133
    - Cancer Treatment Centers of America
- Oregon
  - Bend, Oregon, Spojené státy, 97701
    - Saint Charles Health System
  - Gresham, Oregon, Spojené státy, 97030
    - Legacy Mount Hood Medical Center
  - Portland, Oregon, Spojené státy, 97210
    - Legacy Good Samaritan Hospital and Medical Center
  - Tualatin, Oregon, Spojené státy, 97062
    - Legacy Meridian Park Hospital
- Pennsylvania
  - Abington, Pennsylvania, Spojené státy, 19001
    - Jefferson Abington Hospital
  - Bethlehem, Pennsylvania, Spojené státy, 18015
    - Saint Luke's University Hospital-Bethlehem Campus
  - Bryn Mawr, Pennsylvania, Spojené státy, 19010
    - Bryn Mawr Hospital
  - Danville, Pennsylvania, Spojené státy, 17822
    - Geisinger Medical Center
  - Ephrata, Pennsylvania, Spojené státy, 17522
    - Ephrata Cancer Center
  - Ephrata, Pennsylvania, Spojené státy, 17522
    - Ephrata Community Hospital
  - Gettysburg, Pennsylvania, Spojené státy, 17325
    - Adams Cancer Center
  - Hanover, Pennsylvania, Spojené státy, 17331
    - WellSpan Medical Oncology and Hematology
  - Harrisburg, Pennsylvania, Spojené státy, 17109
    - UPMC Pinnacle Cancer Center/Community Osteopathic Campus
  - Lebanon, Pennsylvania, Spojené státy, 17042
    - Sechler Family Cancer Center
  - Lewisburg, Pennsylvania, Spojené státy, 17837
    - Geisinger Medical Oncology-Lewisburg
  - Paoli, Pennsylvania, Spojené státy, 19301
    - Paoli Memorial Hospital
  - Philadelphia, Pennsylvania, Spojené státy, 19104
    - University of Pennsylvania/Abramson Cancer Center
  - Pittsburgh, Pennsylvania, Spojené státy, 15224
    - West Penn Hospital
  - Sayre, Pennsylvania, Spojené státy, 18840
    - Guthrie Medical Group PC-Robert Packer Hospital
  - West Reading, Pennsylvania, Spojené státy, 19611
    - Reading Hospital
  - Wexford, Pennsylvania, Spojené státy, 15090
    - Wexford Health and Wellness Pavilion
  - Williamsport, Pennsylvania, Spojené státy, 17701
    - UPMC Susquehanna
  - Willow Grove, Pennsylvania, Spojené státy, 19090
    - Asplundh Cancer Pavilion
  - Wynnewood, Pennsylvania, Spojené státy, 19096
    - Lankenau Medical Center
  - York, Pennsylvania, Spojené státy, 17403
    - WellSpan Health-York Hospital
- Rhode Island
  - Providence, Rhode Island, Spojené státy, 02905
    - Women and Infants Hospital
- South Carolina
  - Anderson, South Carolina, Spojené státy, 29621
    - AnMed Health Cancer Center
  - Gaffney, South Carolina, Spojené státy, 29341
    - Gibbs Cancer Center-Gaffney
  - Greenville, South Carolina, Spojené státy, 29607
    - Saint Francis Cancer Center
  - Greenville, South Carolina, Spojené státy, 29601
    - Saint Francis Hospital
  - Greer, South Carolina, Spojené státy, 29651
    - Gibbs Cancer Center-Pelham
  - Hilton Head Island, South Carolina, Spojené státy, 29926-3827
    - South Carolina Cancer Specialists PC
  - Spartanburg, South Carolina, Spojené státy, 29303
    - Spartanburg Medical Center
  - Union, South Carolina, Spojené státy, 29379
    - SMC Center for Hematology Oncology Union
- South Dakota
  - Rapid City, South Dakota, Spojené státy, 57701
    - Rapid City Regional Hospital
  - Sioux Falls, South Dakota, Spojené státy, 57105
    - Avera Cancer Institute
  - Sioux Falls, South Dakota, Spojené státy, 57117-5134
    - Sanford USD Medical Center - Sioux Falls
  - Sioux Falls, South Dakota, Spojené státy, 57104
    - Sanford Cancer Center Oncology Clinic
- Tennessee
  - Kingsport, Tennessee, Spojené státy, 37660
    - Ballad Health Cancer Care - Kingsport
  - Kingsport, Tennessee, Spojené státy, 37660
    - Wellmont Holston Valley Hospital and Medical Center
  - Knoxville, Tennessee, Spojené státy, 37916
    - Covenant Health Cancer Centers
  - Knoxville, Tennessee, Spojené státy, 37932
    - Covenant Health Cancer Centers - West
  - Nashville, Tennessee, Spojené státy, 37232
    - Vanderbilt University/Ingram Cancer Center
- Texas
  - Dallas, Texas, Spojené státy, 75235
    - Parkland Memorial Hospital
  - Dallas, Texas, Spojené státy, 75390
    - UT Southwestern/Simmons Cancer Center-Dallas
  - Houston, Texas, Spojené státy, 77030
    - Houston Methodist Hospital
  - Houston, Texas, Spojené státy, 77070
    - Methodist Willowbrook Hospital
  - Sugar Land, Texas, Spojené státy, 77479
    - Houston Methodist Sugar Land Hospital
- Utah
  - Murray, Utah, Spojené státy, 84107
    - Intermountain Medical Center
  - Salt Lake City, Utah, Spojené státy, 84112
    - Huntsman Cancer Institute/University of Utah
  - Salt Lake City, Utah, Spojené státy, 84106
    - Utah Cancer Specialists-Salt Lake City
  - South Jordan, Utah, Spojené státy, 84009
    - South Jordan Health Center
  - St. George, Utah, Spojené státy, 84770
    - Saint George Regional Medical Center
- Vermont
  - Berlin Corners, Vermont, Spojené státy, 05602
    - Central Vermont Medical Center/National Life Cancer Treatment
  - Burlington, Vermont, Spojené státy, 05401
    - University of Vermont Medical Center
  - Burlington, Vermont, Spojené státy, 05405
    - University of Vermont and State Agricultural College
- Virginia
  - Charlottesville, Virginia, Spojené státy, 22908
    - University of Virginia Cancer Center
  - Richmond, Virginia, Spojené státy, 23235
    - VCU Massey Cancer Center at Stony Point
  - Richmond, Virginia, Spojené státy, 23298
    - VCU Massey Comprehensive Cancer Center
- Washington
  - Bellingham, Washington, Spojené státy, 98225
    - PeaceHealth Saint Joseph Medical Center
  - Edmonds, Washington, Spojené státy, 98026
    - Swedish Cancer Institute-Edmonds
  - Kennewick, Washington, Spojené státy, 99336
    - Kadlec Clinic Hematology and Oncology
  - Mount Vernon, Washington, Spojené státy, 98274
    - Skagit Valley Hospital
  - Mount Vernon, Washington, Spojené státy, 98274
    - Skagit Regional Health Cancer Care Center
  - Seattle, Washington, Spojené státy, 98122
    - Swedish Medical Center-First Hill
  - Seattle, Washington, Spojené státy, 98195
    - University of Washington Medical Center - Montlake
  - Seattle, Washington, Spojené státy, 98104
    - Pacific Gynecology Specialists
  - Seattle, Washington, Spojené státy, 98109
    - Fred Hutchinson Cancer Center
  - Seattle, Washington, Spojené státy, 98133
    - University of Washington Medical Center - Northwest
  - Seattle, Washington, Spojené státy, 98133
    - Women's Cancer Center of Seattle
  - Vancouver, Washington, Spojené státy, 98686
    - Legacy Salmon Creek Hospital
  - Wenatchee, Washington, Spojené státy, 98801
    - Wenatchee Valley Hospital and Clinics
- West Virginia
  - Charleston, West Virginia, Spojené státy, 25304
    - Vandalia Health/CAMC Institute for Academic Medicine
  - Huntington, West Virginia, Spojené státy, 25701
    - Edwards Comprehensive Cancer Center
  - Morgantown, West Virginia, Spojené státy, 26506
    - West Virginia University Healthcare
  - Morgantown, West Virginia, Spojené státy, 26505
    - Monongalia Hospital
- Wisconsin
  - Appleton, Wisconsin, Spojené státy, 54915
    - Ascension Northeast Wisconsin-Saint Elizabeth Cancer Center-Appleton
  - Burlington, Wisconsin, Spojené státy, 53105
    - Aurora Cancer Care-Southern Lakes VLCC
  - Chippewa Falls, Wisconsin, Spojené státy, 54729
    - Marshfield Clinic-Chippewa Center
  - Eau Claire, Wisconsin, Spojené státy, 54701
    - Marshfield Clinic Cancer Center at Sacred Heart
  - Fond du Lac, Wisconsin, Spojené státy, 54937
    - Aurora Health Center-Fond du Lac
  - Germantown, Wisconsin, Spojené státy, 53022
    - Aurora Health Care Germantown Health Center
  - Grafton, Wisconsin, Spojené státy, 53024
    - Aurora Cancer Care-Grafton
  - Green Bay, Wisconsin, Spojené státy, 54311
    - Aurora BayCare Medical Center
  - Green Bay, Wisconsin, Spojené státy, 54301
    - Saint Vincent Hospital Cancer Center Green Bay
  - Green Bay, Wisconsin, Spojené státy, 54303
    - Saint Vincent Hospital Cancer Center at Saint Mary's
  - Kenosha, Wisconsin, Spojené státy, 53142
    - Aurora Cancer Care-Kenosha South
  - La Crosse, Wisconsin, Spojené státy, 54601
    - Gundersen Lutheran Medical Center
  - Ladysmith, Wisconsin, Spojené státy, 54848
    - Marshfield Medical Center - Ladysmith
  - Madison, Wisconsin, Spojené státy, 53792
    - University of Wisconsin Carbone Cancer Center - University Hospital
  - Marinette, Wisconsin, Spojené státy, 54143
    - Aurora Bay Area Medical Group-Marinette
  - Marinette, Wisconsin, Spojené státy, 54143
    - Saint Vincent Hospital Cancer Center at Marinette
  - Marshfield, Wisconsin, Spojené státy, 54449
    - Marshfield Medical Center-Marshfield
  - Mequon, Wisconsin, Spojené státy, 53097
    - Ascension Columbia Saint Mary's Hospital-Ozaukee Campus-Mequon
  - Milwaukee, Wisconsin, Spojené státy, 53226
    - Medical College of Wisconsin
  - Milwaukee, Wisconsin, Spojené státy, 53209
    - Aurora Cancer Care-Milwaukee
  - Milwaukee, Wisconsin, Spojené státy, 53215
    - Aurora Saint Luke's Medical Center
  - Milwaukee, Wisconsin, Spojené státy, 53233
    - Aurora Sinai Medical Center
  - Milwaukee, Wisconsin, Spojené státy, 53211
    - Ascension Columbia Saint Mary's Hospital-Milwaukee Campus
  - Minocqua, Wisconsin, Spojené státy, 54548
    - Marshfield Medical Center - Minocqua
  - Mukwonago, Wisconsin, Spojené státy, 53149
    - ProHealth D N Greenwald Center
  - Oconomowoc, Wisconsin, Spojené státy, 53066
    - ProHealth Oconomowoc Memorial Hospital
  - Oconto Falls, Wisconsin, Spojené státy, 54154
    - Saint Vincent Hospital Cancer Center at Oconto Falls
  - Oshkosh, Wisconsin, Spojené státy, 54904
    - Vince Lombardi Cancer Clinic - Oshkosh
  - Oshkosh, Wisconsin, Spojené státy, 54904
    - Ascension Northeast Wisconsin-Mercy Hospital-Oshkosh
  - Racine, Wisconsin, Spojené státy, 53406
    - Aurora Cancer Care-Racine
  - Rice Lake, Wisconsin, Spojené státy, 54868
    - Marshfield Medical Center-Rice Lake
  - Sheboygan, Wisconsin, Spojené státy, 53081
    - Vince Lombardi Cancer Clinic-Sheboygan
  - Stevens Point, Wisconsin, Spojené státy, 54482
    - Marshfield Medical Center-River Region at Stevens Point
  - Stevens Point, Wisconsin, Spojené státy, 54481
    - Aspirus Cancer Care - Stevens Point
  - Sturgeon Bay, Wisconsin, Spojené státy, 54235-1495
    - Saint Vincent Hospital Cancer Center at Sturgeon Bay
  - Summit, Wisconsin, Spojené státy, 53066
    - Aurora Medical Center in Summit
  - Two Rivers, Wisconsin, Spojené státy, 54241
    - Vince Lombardi Cancer Clinic-Two Rivers
  - Waukesha, Wisconsin, Spojené státy, 53188
    - UW Cancer Center at ProHealth Care
  - Waukesha, Wisconsin, Spojené státy, 53188
    - ProHealth Waukesha Memorial Hospital
  - Wausau, Wisconsin, Spojené státy, 54401
    - Marshfield Clinic-Wausau Center
  - Wauwatosa, Wisconsin, Spojené státy, 53226
    - Aurora Cancer Care-Milwaukee West
  - West Allis, Wisconsin, Spojené státy, 53227
    - Aurora West Allis Medical Center
  - Weston, Wisconsin, Spojené státy, 54476
    - Marshfield Medical Center - Weston
  - Wisconsin Rapids, Wisconsin, Spojené státy, 54494
    - Marshfield Clinic - Wisconsin Rapids Center

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

18 let a starší (Dospělý, Starší dospělý)

Přijímá zdravé dobrovolníky

Pohlaví způsobilá ke studiu

Ženský

Popis

Inclusion Criteria:

Patients must have histologically or cytologically confirmed ovarian cancer, peritoneal cancer or fallopian tube cancer and must have a histological diagnosis of either serous or endometrioid cancer based on local histopathological findings; both endometrioid and serous histology should be high-grade for eligibility of non-mutation carriers; patients with clear cell, mixed epithelial, undifferentiated carcinoma, or transitional cell carcinoma histologies are also eligible, provided that the patient has a known deleterious germline BRCA1 or BRCA2 mutation identified through testing at a clinical laboratory
- Note: Due to the long acceptance of BRCA testing through Myriad, Myriad testing will be accepted; if testing for BRCA is done by other organizations, documentation from a qualified medical professional (e.g., ovarian cancer specialty physician involved in the field, high risk genetics physician, genetics counselor) listing the mutation and confirming that the laboratory results showed a recognized germ line deleterious BRCA 1 or BRCA 2 mutation or BRCA rearrangement is required (12/05/2016); a copy of Myriad or other BRCA mutational analysis (positive or variants of unknown significance [VUS] or negative) reports will be requested but not required for study enrollment
Patients should have recurrent platinum-resistant or- refractory disease - defined as disease that has progressed by imaging while receiving platinum or had recurrence within 6 months of the last receipt of platinum-based chemotherapy; rising CA125 only is not considered as platinum-resistant or refractory disease (12/05/2016)
Phase II study: measurable disease by RECIST 1.1 criteria; if archival tumor sample is not available tumor sample from fresh biopsy is acceptable (12/05/2016)
Phase III study: 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 cancer antigen [CA]125 >= 2 x upper limit of normal [ULN])
No more than 3 prior treatment regimens (including primary therapy; no more than 1 prior non-platinum based therapy in the platinum-resistant/-refractory setting); hormonal therapies used as single agents (i.e. tamoxifen, aromatase inhibitors) will not count towards this line limit (12/05/2016)
Patients may not have had a prior anti-angiogenic agent in the recurrent setting; prior use of bevacizumab in the upfront or upfront maintenance setting is allowed
Patients may not have previously received a PARP-inhibitor
Patient must have provided study specific informed consent prior to study entry
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 or 2
Absolute neutrophil count >= 1,500/mcL (12/05/2016)
Platelets >= 100,000/mcL (12/05/2016)
Hemoglobin >= 10 g/dL (12/05/2016)
Total bilirubin within =< 1.5 times the upper limit of normal (ULN) institutional limits (12/05/2016)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN; if intrahepatic liver metastases are present, AST and ALT must be =< 5 times institutional ULN (12/05/2016)
Creatinine =< 1.5 x the institutional ULN (12/05/2016)
Urine protein: creatinine ratio urine protein creatinine (UPC) of =< 1 OR less than or equal to 2+ proteinuria on two consecutive dipsticks taken no less than 1 week apart; UPC is the preferred test; patients with 2+ proteinuria on dipstick must also have a 24-hour urine collection demonstrating protein of =< 500 mg over 24 hours (12/05/2016)
Toxicities of prior therapy (excepting alopecia) should be resolved to less than or equal to grade 1 as per CTCAE; patients with long-standing stable grade 2 neuropathy may be considered after discussion with the study chair.
Adequately controlled blood pressure (systolic blood pressure [SBP] =< 140; diastolic blood pressure [DBP] =< 90 mmHg) on 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 starting study; 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; blood pressure cuffs will be provided to patients randomized to cediranib alone and the combination of olaparib and cediranib arms (12/05/2016)
Adequately controlled thyroid function, with no symptoms of thyroid dysfunction and thyroid-stimulating hormone (TSH) within normal limits (12/05/2016)
Able to swallow and retain oral medications and without gastrointestinal (GI) illnesses that would preclude absorption of cediranib or olaparib
Age >= 18 years
Cediranib has been shown to terminate fetal development in the rat, as expected for a process dependent on VEGF signaling; for this reason, women of child-bearing potential must have a negative pregnancy test prior to study entry; women of child-bearing potential must agree to use two reliable forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 weeks after cediranib discontinuation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Olaparib adversely affects embryofetal survival and development in the rat; for this reason, women of child-bearing potential must have a negative pregnancy test prior to study entry; women of child-bearing potential must agree to use must agree to use two reliable forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 3 months after the last dose of olaparib; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

Exclusion Criteria:

Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) of starting treatment or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; patients may not have had hormonal therapy within 2 weeks prior to entering the study; patients receiving raloxifene for bone health as per Food and Drug Administration (FDA) indication may remain on raloxifene absent other drug interactions (12/05/2016)
Any other investigational agents within the past 4 weeks
Prior treatment affecting the VEGF/VEGFR pathway or the angiopoietin pathway in the recurrent setting, including but not limited to thalidomide, bevacizumab, sunitinib, sorafenib, pazopanib, cediranib, nintedanib, and trebananib; bevacizumab used in the upfront setting in conjunction with chemotherapy and/or as maintenance to treat newly diagnosed disease will be allowed
Prior use of PARP-inhibitors
CA-125 only disease without Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 measurable or otherwise evaluable disease
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to starting cediranib
Current signs and/or symptoms of bowel obstruction or signs and/or symptoms of bowel obstruction within 3 months prior to starting study drugs
History of intra-abdominal abscess within the past 3 months
History of gastrointestinal perforation; patients with a history of abdominal fistula will be considered eligible if the fistula was surgically repaired or has healed, there has been no evidence of fistula for at least 6 months, and patient is deemed to be at low risk of recurrent fistula (12/05/2016)
Dependency on IV hydration or total parenteral nutrition (TPN)
Any concomitant or prior invasive malignancies with the following curatively treated exceptions:
- Treated limited stage basal cell or squamous cell carcinoma of the skin
- Carcinoma in situ of the breast or cervix
- Primary endometrial cancer meeting the following conditions: stage not greater than IA, grade 1 or 2, no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous/serous, clear cell, or other Federation of Gynecology and Obstetrics (FIGO) grade 3 lesions (12/05/2016)
- Prior cancer treated with a curative intent with no evidence of recurrent disease 5 years following diagnosis and judged by the investigator to be at low risk of recurrence
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 drug
Patients with any of the following:
- History of myocardial infarction within six months
- 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
  - 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
Clinical significant peripheral vascular disease or vascular disease (aortic aneurysm or aortic dissection)
Evidence of coagulopathy or bleeding diathesis; therapeutic anticoagulation for prior thromboembolic events is permitted
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)
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
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 (12/05/2016)
Known human immunodeficiency virus (HIV)-positive individuals are ineligible because of the potential for pharmacokinetic interactions with cediranib or olaparib; in addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy
Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible
- Strong inhibitors and inducers of UGT/PgP should be used with caution (12/05/2016)
Pregnant women are excluded from this study because cediranib and olaparib are agents with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with cediranib and olaparib, breastfeeding should be discontinued if the mother is treated with cediranib or olaparib; these potential risks may also apply to other agents used in this study

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

Primární účel: Léčba
Přidělení: Randomizované
Intervenční model: Paralelní přiřazení
Maskování: Žádné (otevřený štítek)

Počet zbraní

Zbraně a zásahy

Skupina účastníků / Arm	Intervence / Léčba
Aktivní komparátor: Phase II Arm I (reference regimen) Patients undergo physician's choice of standard of care chemotherapy, comprising either paclitaxel IV over 60 minutes on days 1, 8, 15, and 22 every 28 days (Regimen I); pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1 every 28 days (Regimen II); or topotecan hydrochloride IV over 30 minutes on days 1, 8, and 15 every 28 days or days 1-5 every 21 days (Regimen III). Treatment continues in the absence of disease progression or unacceptable toxicity. No modification of the assigned regimens, such as additional drugs (gemcitabine, or bevacizumab) is allowed. Patients also undergo CT and MRI throughout the study. (12/05/2016)	Lék: Paclitaxel Given IV Ostatní jména: Taxol Anzatax Asotax Bristaxol Praxel Taxol Konzentrat Postup: Computed Tomography Undergo CT Ostatní jména: ČT KOČKA CAT skenování Počítačová axiální tomografie Počítačová tomografie CT vyšetření tomografie Počítačová axiální tomografie (postup) Počítačová tomografie (CT). Diagnostické skenování CAT Typ služby diagnostického skenování CAT Postup: Magnetic Resonance Imaging Undergo MRI Ostatní jména: MRI Magnetická rezonance Skenování magnetickou rezonancí Lékařské zobrazování, magnetická rezonance / nukleární magnetická rezonance PAN MR zobrazování MRI skenování NMR zobrazování NMRI Nukleární magnetická rezonance Zobrazování magnetickou rezonancí (MRI) sMRI Magnetická rezonance (postup) Strukturální MRI Jiný: Questionnaire Administration Ancillary studies Lék: Pegylated Liposomal Doxorubicin Hydrochloride Given IV Ostatní jména: ATI-0918 Caelyx Doxil Doxilen Lipozom doxorubicin HCl Duomeisu Evacet LipoDox Liposomální adriamycin Liposomálně zapouzdřený doxorubicin Pegylovaný doxorubicin HCl liposom S-liposomální doxorubicin Stealth liposomální doxorubicin TLC D-99 Dox-SL Lipozomální doxorubicin HCl Lipozom doxorubicin hydrochlorid Lipodox 50 Liposomální doxorubicin hydrochlorid Pegylovaný liposomální doxorubicin Doxorubicin lipozomální Lék: Topotecan Given IV Ostatní jména: Hycamptamin Topotekan lakton Lék: Topotecan Hydrochloride Given IV Ostatní jména: Hycamtin Hycamptamin SKF S-104864-A Topotekan HCl topotekan hydrochlorid (perorální) Potactasol Evotopin Topotec Nogitecan hydrochlorid SKF S 104864 A SKF S104864A
Experimentální: Phase II Arm II (cediranib maleate, olaparib) Patients receive cediranib maleate PO QD and olaparib PO BID. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout the study.	Postup: Computed Tomography Undergo CT Ostatní jména: ČT KOČKA CAT skenování Počítačová axiální tomografie Počítačová tomografie CT vyšetření tomografie Počítačová axiální tomografie (postup) Počítačová tomografie (CT). Diagnostické skenování CAT Typ služby diagnostického skenování CAT Postup: Magnetic Resonance Imaging Undergo MRI Ostatní jména: MRI Magnetická rezonance Skenování magnetickou rezonancí Lékařské zobrazování, magnetická rezonance / nukleární magnetická rezonance PAN MR zobrazování MRI skenování NMR zobrazování NMRI Nukleární magnetická rezonance Zobrazování magnetickou rezonancí (MRI) sMRI Magnetická rezonance (postup) Strukturální MRI Jiný: Questionnaire Administration Ancillary studies Lék: Cediranib Maleate Given PO Ostatní jména: AZD2171 AZD2171 maleát Recentin Lék: Olaparib Given PO Ostatní jména: Lynparza AZD 2281 AZD-2281 AZD2281 KU-0059436 Inhibitor PARP AZD2281 KU0059436 Olanib Olaparix KU 0059436 Lék: Cediranib Given PO Ostatní jména: AZD2171 AZ-D2171 AZD 2171
Experimentální: Phase II Arm III (cediranib maleate) Patients receive cediranib maleate PO daily continuously. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout the study.	Postup: Computed Tomography Undergo CT Ostatní jména: ČT KOČKA CAT skenování Počítačová axiální tomografie Počítačová tomografie CT vyšetření tomografie Počítačová axiální tomografie (postup) Počítačová tomografie (CT). Diagnostické skenování CAT Typ služby diagnostického skenování CAT Postup: Magnetic Resonance Imaging Undergo MRI Ostatní jména: MRI Magnetická rezonance Skenování magnetickou rezonancí Lékařské zobrazování, magnetická rezonance / nukleární magnetická rezonance PAN MR zobrazování MRI skenování NMR zobrazování NMRI Nukleární magnetická rezonance Zobrazování magnetickou rezonancí (MRI) sMRI Magnetická rezonance (postup) Strukturální MRI Jiný: Questionnaire Administration Ancillary studies Lék: Cediranib Maleate Given PO Ostatní jména: AZD2171 AZD2171 maleát Recentin Lék: Cediranib Given PO Ostatní jména: AZD2171 AZ-D2171 AZD 2171
Experimentální: Phase II Arm IV (olaparib) Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout the study. (In July 2018, the Data Monitoring Committee voted to exclude the olaparib alone regimen).	Postup: Computed Tomography Undergo CT Ostatní jména: ČT KOČKA CAT skenování Počítačová axiální tomografie Počítačová tomografie CT vyšetření tomografie Počítačová axiální tomografie (postup) Počítačová tomografie (CT). Diagnostické skenování CAT Typ služby diagnostického skenování CAT Postup: Magnetic Resonance Imaging Undergo MRI Ostatní jména: MRI Magnetická rezonance Skenování magnetickou rezonancí Lékařské zobrazování, magnetická rezonance / nukleární magnetická rezonance PAN MR zobrazování MRI skenování NMR zobrazování NMRI Nukleární magnetická rezonance Zobrazování magnetickou rezonancí (MRI) sMRI Magnetická rezonance (postup) Strukturální MRI Jiný: Questionnaire Administration Ancillary studies Lék: Olaparib Given PO Ostatní jména: Lynparza AZD 2281 AZD-2281 AZD2281 KU-0059436 Inhibitor PARP AZD2281 KU0059436 Olanib Olaparix KU 0059436
Aktivní komparátor: Phase III Arm I (reference regimen) Patients undergo physician's choice standard of care chemotherapy as in Phase II Arm I. No modification of the assigned regimens, such as additional drugs (gemcitabine or bevacizumab) is allowed. Patients also undergo CT and MRI throughout the study. (12/05/2016)	Lék: Paclitaxel Given IV Ostatní jména: Taxol Anzatax Asotax Bristaxol Praxel Taxol Konzentrat Postup: Computed Tomography Undergo CT Ostatní jména: ČT KOČKA CAT skenování Počítačová axiální tomografie Počítačová tomografie CT vyšetření tomografie Počítačová axiální tomografie (postup) Počítačová tomografie (CT). Diagnostické skenování CAT Typ služby diagnostického skenování CAT Postup: Magnetic Resonance Imaging Undergo MRI Ostatní jména: MRI Magnetická rezonance Skenování magnetickou rezonancí Lékařské zobrazování, magnetická rezonance / nukleární magnetická rezonance PAN MR zobrazování MRI skenování NMR zobrazování NMRI Nukleární magnetická rezonance Zobrazování magnetickou rezonancí (MRI) sMRI Magnetická rezonance (postup) Strukturální MRI Jiný: Questionnaire Administration Ancillary studies Lék: Pegylated Liposomal Doxorubicin Hydrochloride Given IV Ostatní jména: ATI-0918 Caelyx Doxil Doxilen Lipozom doxorubicin HCl Duomeisu Evacet LipoDox Liposomální adriamycin Liposomálně zapouzdřený doxorubicin Pegylovaný doxorubicin HCl liposom S-liposomální doxorubicin Stealth liposomální doxorubicin TLC D-99 Dox-SL Lipozomální doxorubicin HCl Lipozom doxorubicin hydrochlorid Lipodox 50 Liposomální doxorubicin hydrochlorid Pegylovaný liposomální doxorubicin Doxorubicin lipozomální Lék: Topotecan Given IV Ostatní jména: Hycamptamin Topotekan lakton Lék: Topotecan Hydrochloride Given IV Ostatní jména: Hycamtin Hycamptamin SKF S-104864-A Topotekan HCl topotekan hydrochlorid (perorální) Potactasol Evotopin Topotec Nogitecan hydrochlorid SKF S 104864 A SKF S104864A
Experimentální: Phase III Arm II (cediranib maleate, olaparib) Patients receive cediranib maleate PO and olaparib PO as in Phase II Arm II. Patients also undergo CT and MRI throughout the study.	Postup: Computed Tomography Undergo CT Ostatní jména: ČT KOČKA CAT skenování Počítačová axiální tomografie Počítačová tomografie CT vyšetření tomografie Počítačová axiální tomografie (postup) Počítačová tomografie (CT). Diagnostické skenování CAT Typ služby diagnostického skenování CAT Postup: Magnetic Resonance Imaging Undergo MRI Ostatní jména: MRI Magnetická rezonance Skenování magnetickou rezonancí Lékařské zobrazování, magnetická rezonance / nukleární magnetická rezonance PAN MR zobrazování MRI skenování NMR zobrazování NMRI Nukleární magnetická rezonance Zobrazování magnetickou rezonancí (MRI) sMRI Magnetická rezonance (postup) Strukturální MRI Jiný: Questionnaire Administration Ancillary studies Lék: Cediranib Maleate Given PO Ostatní jména: AZD2171 AZD2171 maleát Recentin Lék: Olaparib Given PO Ostatní jména: Lynparza AZD 2281 AZD-2281 AZD2281 KU-0059436 Inhibitor PARP AZD2281 KU0059436 Olanib Olaparix KU 0059436 Lék: Cediranib Given PO Ostatní jména: AZD2171 AZ-D2171 AZD 2171
Experimentální: Phase III Arm III (single-agent cediranib maleate) Patients receive cediranib maleate PO as determined by the Phase II study. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout the study.	Postup: Computed Tomography Undergo CT Ostatní jména: ČT KOČKA CAT skenování Počítačová axiální tomografie Počítačová tomografie CT vyšetření tomografie Počítačová axiální tomografie (postup) Počítačová tomografie (CT). Diagnostické skenování CAT Typ služby diagnostického skenování CAT Postup: Magnetic Resonance Imaging Undergo MRI Ostatní jména: MRI Magnetická rezonance Skenování magnetickou rezonancí Lékařské zobrazování, magnetická rezonance / nukleární magnetická rezonance PAN MR zobrazování MRI skenování NMR zobrazování NMRI Nukleární magnetická rezonance Zobrazování magnetickou rezonancí (MRI) sMRI Magnetická rezonance (postup) Strukturální MRI Jiný: Questionnaire Administration Ancillary studies Lék: Cediranib Maleate Given PO Ostatní jména: AZD2171 AZD2171 maleát Recentin Lék: Cediranib Given PO Ostatní jména: AZD2171 AZ-D2171 AZD 2171

Co je měření studie?

Primární výstupní opatření

Měření výsledku	Popis opatření	Časové okno
Progression-free Survival (PFS) (Phase II Only) Časové okno: The protocol required lesion assessments every 9 weeks from cycle 1, day 1 for the first year, then every 12 weeks thereafter until disease progression. Approximately 42 months.	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 follow-up were censored on the date of last CT Scan, or the CT Scan date prior to two missed assessments. Disease progression is defined 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. (Note: the appearance of one or more new lesions is also considered progression).	The protocol required lesion assessments every 9 weeks from cycle 1, day 1 for the first year, then every 12 weeks thereafter until disease progression. Approximately 42 months.
Progression-free Survival (PFS) (Phase III Only) Časové okno: The protocol required lesion assessments every 9 weeks from cycle 1, day 1 for the first year, then every 12 weeks thereafter until disease progression. Approximately 42 months.	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 follow-up were censored on the date of last CT Scan, or the CT Scan date prior to two missed assessments. Disease progression is defined 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. (Note: the appearance of one or more new lesions is also considered progression).	The protocol required lesion assessments every 9 weeks from cycle 1, day 1 for the first year, then every 12 weeks thereafter until disease progression. Approximately 42 months.
Overall Survival (OS) (Phase III Only) Časové okno: Time from study enrollment to death due to any cause, assessed up to 5 years	Overall survival will be evaluated. To allow for better understanding of time to subsequent therapy and OS, patients on experimental study drug(s) or standard chemotherapy arm will be followed after progression, with data capture to include the date of initiation of the subsequent therapy, detailed information on the type of subsequent therapy received, and time to progression on the subsequent therapy.	Time from study enrollment to death due to any cause, assessed up to 5 years

Sekundární výstupní opatření

Měření výsledku	Popis opatření	Časové okno
Objective Response Rate (Complete Response and Partial Response) (Phase II Only) Časové okno: Up to 5 years	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. A Complete response (CR) is defined as the complete disappearance of all target lesions, while a Partial response (PR) is defined as at least a 30% decrease in the sum of the longest diameters of target lesions compared to the baseline measurement; essentially, the tumor shrinks significantly but does not completely disappear. Overall response (OR) = CR + PR.	Up to 5 years
Objective Response Rate (Complete Response and Partial Response for Phase III Only) Časové okno: Up to 5 years	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. A Complete response (CR) is defined as the complete disappearance of all target lesions, while a Partial response (PR) is defined as at least a 30% decrease in the sum of the longest diameters of target lesions compared to the baseline measurement; essentially, the tumor shrinks significantly but does not completely disappear. Overall response (OR) = CR + PR.	Up to 5 years
Incidence of Grade 3 (or Higher) Adverse Events Časové okno: Up to 5 years	Adverse events will be categorized by CTCAE V4.0. This outcome will report the count of participants who experienced a grade 3 (or higher) adverse event.	Up to 5 years

Další výstupní opatření

Měření výsledku	Popis opatření	Časové okno
Patient-reported Scores of Disease-related Symptoms Časové okno: Up to 5 years	Measured by the 9-item Disease Related Symptoms (DRS-9) subscale of the National Comprehensive Cancer Network (NCCN)-Functional Assessment of Cancer Therapy (FACT) Ovarian Symptom Index (NFOSI-18).	Up to 5 years
Gene Mutations Assessed BROCA-HR Časové okno: Up to 5 years	A single proportional hazards model will be used to estimate the treatment hazard ratios (and variances) for each of the experimental treatments selected for phase III evaluation relative to the reference treatment (chemotherapy) group. The model will include adjustments for prior platinum-free interval, prior bevacizumab treatment, age at study enrollment, randomly assigned study treatment and BROCA-HR status. The estimated hazard ratio(s) for BROCA-HR and the corresponding confidence intervals will be depicted with a forest plot, and assessed for qualitative interaction(s).	Up to 5 years
Change in Circulating Endothelial Cell Levels Časové okno: Baseline up to 5 years	A proportional hazards model will be used to assess a linear association between the change in circulating endothelial cell values and the log relative hazard of death within each treatment group. Sensitivity analyses will include known prognostic factors in the model. A plot of the martingale residuals or estimated relative hazards by change in circulating endothelial cell quintiles will be used to qualitatively assess the assumption of a linear relationship between the change in circulating endothelial cell values and the log relative hazard.	Baseline up to 5 years
Biomarkers in Plasma Angiome Časové okno: Up to 5 years	A proportional hazards model will be used to assess whether the pretreatment values of any of these analytes have a prognostic association with overall survival. The model will include clinical covariates: age, performance status, and the randomly assigned study treatment. Proportional hazards models will be used to assess the relationship between patients' analyte values and log hazard. A proportional hazards model will be used to assess the potential predictive associations between analytes, treatment and survival.	Up to 5 years

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

National Cancer Institute (NCI)

Spolupracovníci

NRG Oncology

Canadian Cancer Trials Group

Vyšetřovatelé

Vrchní vyšetřovatel: Jung-min Lee, NRG Oncology

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Lee JM, Brady MF, Miller A, Moore RG, MacKay H, McNally L, Lea J, Street D, Lheureux S, McDonald ME, Duska LR, Cantuaria G, Kavecansky J, Leath CA 3rd, Powell M, Cadungog MG, Rose PG, Kim YM, Huang HQ, Provencher M, Wenzel LB, Bookman MA, Kohn EC, Secord AA. Cediranib and Olaparib Combination Compared With Cediranib or Olaparib Alone, or Chemotherapy in Platinum-Resistant or Primary Platinum-Refractory Ovarian Cancer: NRG-GY005. J Clin Oncol. 2024 Dec 20;42(36):4305-4316. doi: 10.1200/JCO.24.00683. Epub 2024 Oct 3.

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Aktuální)

3. května 2016

Primární dokončení (Aktuální)

12. června 2023

Dokončení studie (Odhadovaný)

4. března 2027

Termíny zápisu do studia

První předloženo

17. července 2015

První předloženo, které splnilo kritéria kontroly kvality

17. července 2015

První zveřejněno (Odhadovaný)

20. července 2015

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

1. října 2026

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

30. září 2026

Naposledy ověřeno

1. září 2026

Více informací

Termíny související s touto studií

Další relevantní podmínky MeSH

Další identifikační čísla studie

NCI-2015-00651
U10CA180868 (Grant/smlouva NIH USA)
NCI-2015-00651 (Identifikátor registru: CTRP (Clinical Trial Reporting Program))
NRG-GY005 (Jiný identifikátor: CTEP)
s16-01681
NRG-GY005
NRG-GY005 (Jiný identifikátor: NRG Oncology)

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

Testování kombinace Cediranibu a Olaparibu ve srovnání s každým lékem samotným nebo jinou chemoterapií u recidivujícího karcinomu vaječníků rezistentního na platinu

Randomizovaná studie fáze II/III kombinace cediranibu a olaparibu ve srovnání s cediranibem nebo olaparibem samotným nebo standardní chemoterapií u žen s recidivující platinou rezistentní nebo refrakterní rakovinou vaječníků, vejcovodů nebo primárním karcinomem peritonea (COCOS)

Přehled studie

Postavení

Podmínky

Intervence / Léčba

Detailní popis

Typ studie

Zápis (Aktuální)

Fáze

Kontakty a umístění

Studijní místa

Kritéria účasti

Kritéria způsobilosti

Věk způsobilý ke studiu

Přijímá zdravé dobrovolníky

Pohlaví způsobilá ke studiu

Popis

Studijní plán

Jak je studie koncipována?

Detaily designu

Počet zbraní

Zbraně a zásahy

Skupina účastníků / Arm

Intervence / Léčba

Co je měření studie?

Primární výstupní opatření

Měření výsledku

Popis opatření

Časové okno

Sekundární výstupní opatření

Měření výsledku

Popis opatření

Časové okno

Další výstupní opatření

Měření výsledku

Popis opatření

Časové okno

Spolupracovníci a vyšetřovatelé

Sponzor

Spolupracovníci

Vyšetřovatelé

Publikace a užitečné odkazy

Obecné publikace

Termíny studijních záznamů

Hlavní termíny studia

Začátek studia (Aktuální)

Primární dokončení (Aktuální)

Dokončení studie (Odhadovaný)

Termíny zápisu do studia

První předloženo

První předloženo, které splnilo kritéria kontroly kvality

První zveřejněno (Odhadovaný)

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

Naposledy ověřeno

Více informací

Termíny související s touto studií

Další relevantní podmínky MeSH

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