GA NCORP

NCORP Trials

Testing the Combination of Cediranib and Olaparib in Comparison to Each Drug Alone or Other Chemotherapy in Recurrent Platinum-Resistant Ovarian Cancer

Status
Closed
Cancer Type
Gynecologic Cancers
Ovarian Cancer
Primary Peritoneal Cancer
Trial Phase
Phase II
Phase III
Eligibility
18 Years and older, Female
Study Type
Treatment
NCD ID
NCT02502266
Protocol IDs
NRG-GY005 (primary)
NCI-2015-00651
Study Sponsor
NRG Oncology

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 (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.

Objectives

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) 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. No modification of the assigned regimens, such as additional drugs (gemcitabine, or bevacizumab) is allowed. (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.

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

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. (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. (12/05/2016)

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 cediranib maleate PO as determined by the Phase II study. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Treatment Sites


Atlanta Cancer Care - Alpharetta
3400 C Old Milton Parkway
Suite 400
Alpharetta, GA 30005
Kristin Sieverding
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
Renee Gaiter
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
Andrena Jefferson
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
Jen Cuvo
404-303-3355
www.geraldfeuer.com

Georgia Cancer Specialists - Athens
125 King Avenue
Suite 200
Athens, GA 30606
Cynthia Pirkle
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
Anila Lokhandwala
404-256-4777 ext 9242
www.gacancer.com

Georgia Cancer Specialists - Kennestone
790 Church Street
Suite 335
Marietta, GA 30060
Greta Dudley
www.gacancer.com

Georgia Cancer Specialists - Macon-Coliseum
308 Coliseum Drive
Suite 120
Macon, GA 31217
Sonia Hernandez
478-745-6130 x8152
www.gacancer.com

Georgia Cancer Specialists - Stemmer
2712 Lawrenceville Highway
Decatur, GA 30033
Nina Patel
770-496-5555
www.gacancer.com

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

Northside Hospital Cancer Institute
1000 Johnson Ferry Road NE
Atlanta, GA 30342
Northside Hospital Central Research Department
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

University Gynecologic Oncology
960 Johnson Ferry Road
Suite 130
Atlanta, GA 30342
Jen Cuvo
404-303-3355
www.ugynonc.com

 
For a complete listing of all trial sites in Georgia, please visit GeorgiaCancerInfo.org