Return to Clinical Trials Search Results

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)

Phase II Study Primary Objective: To assess the efficacy and identify (in)active arm(s) of the combination of cediranib and olaparib, cediranib alone, olaparib alone, and physician's choice standard of care chemotherapy, as measured by PFS in the setting of recurrent platinum-resistant or-refractory ovarian, primary peritoneal or fallopian tube cancer. Phase II Study Secondary Objectives: 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 RECIST criteria, in the setting of recurrent platinum-resistant or-refractory ovarian, primary peritoneal or fallopian tube cancer. To assess safety endpoints, as measured by frequency and severity of adverse events by Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. Phase II Study Objectives with Integrated Biomarkers: To assess correlation of homologous recombination deficiency (HRD) status, as assessed via BROCA-HR assay with response, as measured by PFS and ORR. To evaluate the prognostic and predictive role of circulating endothelial cells (CEC) on comparative effectiveness of targeted therapies and reference chemotherapy. To evaluate quality of life data compliance, as measured by the 9-item Disease Related Symptoms (DRS-P) subscale of the NCCN-FACT Ovarian Symptom Index (NFOSI) for utilization and analysis in the Phase III study. Additional QOL/PRO items will be collected, as proposed in 1.8.2. Phase II Study Exploratory Objectives: 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. To evaluate the prognostic and predictive role of angiogenic biomarkers, as assessed by the Duke plasma angiome. Phase III Study Primary Objective: To assess the efficacy of the combination of cediranib and olaparib, and active monotherapy experimental arm(s) from Randomized Phase II, as measured by 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 Study Secondary Objectives: To assess the efficacy of the combination of cediranib and olaparib, and active monotherapy experimental arm(s) from Randomized Phase II, 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. To assess safety endpoints, as measured by frequency and severity of adverse events by Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. Phase III Study Objectives with Integrated Biomarkers: To assess correlation of HRD status, as assessed via BROCA-HR assay with response, as measured by OS, PFS and ORR. To evaluate the prognostic and predictive role of circulating endothelial cells (CEC) on comparative effectiveness of targeted therapies and reference chemotherapy. 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 or olaparib and combination, compared to standard chemotherapy, in the setting of recurrent platinum-resistant or-refractory ovarian, primary peritoneal or fallopian tube cancer. Please see protocol for Phase III Trial Exploratory Objectives.

Phase II Study Primary Objective: To assess the efficacy and identify (in)active arm(s) of the combination of cediranib and olaparib, cediranib alone, olaparib alone, and physician's choice standard of care chemotherapy, as measured by PFS in the setting of recurrent platinum-resistant or-refractory ovarian, primary peritoneal or fallopian tube cancer. Phase II Study Secondary Objectives: 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 RECIST criteria, in the setting of recurrent platinum-resistant or-refractory ovarian, primary peritoneal or fallopian tube cancer. To assess safety endpoints, as measured by frequency and severity of adverse events by Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. Phase II Study Objectives with Integrated Biomarkers: To assess correlation of homologous recombination deficiency (HRD) status, as assessed via BROCA-HR assay with response, as measured by PFS and ORR. To evaluate the prognostic and predictive role of circulating endothelial cells (CEC) on comparative effectiveness of targeted therapies and reference chemotherapy. To evaluate quality of life data compliance, as measured by the 9-item Disease Related Symptoms (DRS-P) subscale of the NCCN-FACT Ovarian Symptom Index (NFOSI) for utilization and analysis in the Phase III study. Additional QOL/PRO items will be collected, as proposed in 1.8.2. Phase II Study Exploratory Objectives: 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. To evaluate the prognostic and predictive role of angiogenic biomarkers, as assessed by the Duke plasma angiome. Phase III Study Primary Objective: To assess the efficacy of the combination of cediranib and olaparib, and active monotherapy experimental arm(s) from Randomized Phase II, as measured by 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 Study Secondary Objectives: To assess the efficacy of the combination of cediranib and olaparib, and active monotherapy experimental arm(s) from Randomized Phase II, 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. To assess safety endpoints, as measured by frequency and severity of adverse events by Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. Phase III Study Objectives with Integrated Biomarkers: To assess correlation of HRD status, as assessed via BROCA-HR assay with response, as measured by OS, PFS and ORR. To evaluate the prognostic and predictive role of circulating endothelial cells (CEC) on comparative effectiveness of targeted therapies and reference chemotherapy. 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 or olaparib and combination, compared to standard chemotherapy, in the setting of recurrent platinum-resistant or-refractory ovarian, primary peritoneal or fallopian tube cancer. Please see protocol for Phase III Trial Exploratory Objectives.