Georgia's Online Cancer Information Center

Find A Clinical Trial

A Randomized Phase II/III Study of the Combination of Cediranib and Olaparib Compared to Cediranib or Olaparib Alone, or Standard of Care Chemotherapy in Women with Recurrent Platinum-Resistant or -Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (COCOS)

Status
Active
Cancer Type
Ovarian Cancer
Trial Phase
Phase II
Phase III
Eligibility
18 and over, Male and Female
Study Type
Biomarker/Laboratory analysis
Treatment
NCT ID
NCT02502266
Protocol IDs
NRG-GY005 (primary)
NCI-2015-00651
Study Sponsor
National Cancer Institute

Summary

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 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. Drugs used in chemotherapy 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.

Objectives

PRIMARY OBJECTIVES:

I. To assess the efficacy and identify (in)active arm(s) of the combination of cediranib (cediranib maleate) 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 active arm(s) from Randomized Phase II, as measured by overall survival (OS), 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, as measured by objective response rate (ORR: partial or complete response) by Response Evaluation Criteria in Solid Tumors (RECIST) 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) version (v).4.0. (Phase II)

III. To assess the efficacy of active arm(s) from Randomized Phase II, as measured by ORR and PFS, 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)

TERTIARY OBJECTIVES:

I. To collect quality of life data, 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)

II. Assess the effect on quality of life, as assessed through disease-related symptoms (DRS) as measured by the DRS-related items of NCCN-FACT Ovarian Symptom Index-18 (NFOSI-18), of single agent olaparib or cediranib and combination, compared to standard chemotherapy, in the setting of recurrent platinum-resistant or-refractory ovarian, primary peritoneal or fallopian tube cancer. (Phase III)

III. To assess the effect on secondary measures of quality of life, important treatment side effects (TSE), function / well-being, and general quality of life, as measured by NFOSI-18, and FACT/Gynecological Oncology Group (GOG)-Neurotoxicity (NTX)-4, and the Euroqol EQ-5-dimension (5D), of single agent olaparib or cediranib and combination, compared to standard chemotherapy, in the setting of recurrent platinum-resistant or-refractory ovarian, primary peritoneal or fallopian tube cancer. (Phase III)

VI. To assess the relative cost-effectiveness of the active arms from randomized Phase II as assessed with the use of OS, EQ5D instrument, and healthcare resource utilization collection in women with recurrent platinum-resistant or-refractory ovarian, primary peritoneal or fallopian tube cancer. (Phase III)

V. To assess correlation of response and effect of homologous recombination deficiency (HRD) status, as assessed via BROCA-HR assay, on comparative effectiveness of active targeted therapy and reference chemotherapy regimens. (Phase III)

VI. To evaluate the prognostic and predictive role of angiogenic biomarkers, as assessed by the Duke plasma angiome and circulating endothelial cells (CEC). (Phase III)

VII. To assess exploratory biomarkers of potential HRD, including genomic scarring, breast cancer, early onset 1 (BRCA1) methylation, BRCA1 protein expression, and mutations in non-homologous end joining (NHEJ), and other genes that might modify HRD. (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) on days 1, 8, 15, and 22 every 28 days (Regimen I); pegylated liposomal doxorubicin hydrochloride IV on day 1 every 28 days (Regimen II); or topotecan hydrochloride IV 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.

ARM II (CEDIRANIB MALEATE AND OLAPARIB): Patients receive cediranib maleate orally (PO) and olaparib PO as determined from an ongoing Phase I study. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM III (CEDIRANIB): Patients receive cediranib maleate PO daily continuously. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM IV (OLAPARIB): Patients receive olaparib PO twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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.

ARM II (CEDIRANIB AND OLAPARIB): Patients receive cediranib maleate PO and olaparib PO as in Phase II Arm II.

ARM III (SINGLE AGENT): Patients receive either olaparib maleate PO or cediranib PO, as determined by the Phase II study. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 4 months for up to 3 years.

Treatment Sites in Georgia

Atlanta Cancer Care - Alpharetta


3400 C Old Milton Parkway
Suite 400
Alpharetta, GA 30005
770-777-1315
www.atlantacancercare.com

Atlanta Cancer Care - Conyers


1498 Klondike Road
Suite 106
Conyers, GA 30094
404-303-3355
www.atlantacancercare.com

Atlanta Cancer Care - Cumming


1505 Northside Boulevard
Suite 4600
Cumming, GA 30041
770-205-5292 x1041
www.atlantacancercare.com

Atlanta Cancer Care - Decatur


2545 Lawrenceville Highway
Suite 300
Decatur, GA 30033
404-303-3355
www.atlantacancercare.com

Atlanta Cancer Care - Stockbridge


7813 Spivey Station Boulevard
Suite 210
Jonesboro, GA 30236
678 466-2069
www.atlantacancercare.com

Atlanta Cancer Care - Tower


5670 Peachtree Dunwoody Road
Suite 1100
Atlanta, GA 30342
404-303-3355
www.atlantacancercare.com

Atlanta Gynecologic Oncology


980 Johnson Ferry Road
Suite 900
Atlanta, GA 30342
404-303-3355
www.geraldfeuer.com

Augusta University Medical Center


1120 15th Street
Augusta, GA 30912
706-721-4430
www.augustahealth.org

Emory University Hospital - Midtown


550 Peachtree Street NE
Atlanta, GA 30308
404-686-4411
www.emoryhealthcare.org

Georgia Cancer Specialists - Athens


125 King Avenue
Suite 200
Athens, GA 30606
www.gacancer.com

Georgia Cancer Specialists - Canton


228 Riverstone Drive
Canton, GA 30114
www.gacancer.com

Georgia Cancer Specialists - CenterPointe


1100 Johnson Ferry Road
Suite 600
Sandy Springs, GA 30342
404-256-4777 ext 9242
www.gacancer.com

Georgia Cancer Specialists - Kennestone


790 Church Street
Suite 335
Marietta, GA 30060
www.gacancer.com

Georgia Cancer Specialists - Macon-Coliseum


308 Coliseum Drive
Suite 120
Macon, GA 31217
478-745-6130 x8152
www.gacancer.com

Georgia Cancer Specialists - Stemmer


2712 Lawrenceville Highway
Decatur, GA 30033
770-496-5555
www.gacancer.com

Georgia Gynecologic Oncology


980 Johnson Ferry Road
Suite 910
Atlanta, GA 30342
404-303-3355
www.ggo-atl.com/

Northside Hospital Cancer Institute


1000 Johnson Ferry Road NE
Atlanta, GA 30342
404-303-3355
www.northside.com

Northside Hospital Cancer Institute - Forsyth


1200 Northside Forsyth Drive
Suite 140
Cumming, GA 30041
404-303-3355
www.northside.com

Piedmont Hospital - Atlanta


1968 Peachtree Road, NW
Atlanta, GA 30309
www.piedmont.org

University Gynecologic Oncology


960 Johnson Ferry Road
Suite 130
Atlanta, GA 30342
404-303-3355
www.ugynonc.com

WellStar Cobb Hospital


3950 Austell Road
Austell, GA 30106
770-793-5980
www.wellstar.org

WellStar Kennestone Hospital


677 Church Street
Marietta, GA 30060
770-793-5980
www.wellstar.org

WellStar North Fulton Hospital


3000 Hospital Boulevard
Roswell, GA 30076
770-751-2556
www.wellstar.org

Winship Cancer Institute of Emory University


1365 Clifton Road NE
Building C
Atlanta, GA 30322
404-778-5180
winshipcancer.emory.edu

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.
Georgia CORE

 

Advancing Cancer Care through Partnerships and Innovation

Georgia CORE is a statewide nonprofitthat leverages partnerships and innovation to attract more clinical trials, increase research, and promote education and early detection to improve cancer care for Georgians in rural, urban, and suburban communities across the state.