Cediranib Maleate and Olaparib in Treating Patients With Recurrent Ovarian, Fallopian Tube, Peritoneal Cancer, or Triple-Negative Breast Cancer
There are two parts to this study. The first part of this research study has the purpose of determining the safety of the combination of the two drugs cediranib maleate and olaparib and the highest doses of these two drugs that can be given in combination to people safely. Cediranib maleate is a drug that may help keep cancer cells from growing by affecting their blood supply. Olaparib is a drug that may stop cancer cells from growing abnormally. These drugs have been used in other research studies in ovarian and breast cancer, and information from those other research studies suggest that these may help to keep cancer from growing in this research study. This study is now entering the second part of the study, where we are comparing the effects of the combination of olaparib and cediranib maleate to that of olaparib only in women with certain types of recurrent ovarian, fallopian tube, or primary peritoneal cancers.
Estrogen Receptor-negative Breast Cancer
HER2-negative Breast Cancer
Ovarian Endometrioid Adenocarcinoma
Ovarian Papillary Serous Carcinoma
Ovarian Serous Cystadenocarcinoma
Progesterone Receptor-negative Breast Cancer
Recurrent Breast Cancer
Recurrent Fallopian Tube Cancer
Recurrent Ovarian Epithelial Cancer
Recurrent Primary Peritoneal Cavity Cancer
Triple-negative Breast Cancer
Drug: cediranib maleate
Other: laboratory biomarker analysis
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Cediranib and Olaparib in Combination for Treatment of Recurrent Papillary-Serous Ovarian, Fallopian Tube, or Peritoneal Cancer or for Treatment of Recurrent Triple-Negative Breast Cancer|
- Dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of cediranib maleate in combination with olaparib (Phase I) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
- Progression-free survival at the MTD/recommended phase 2 dose (RP2D) of cediranib maleate with olaparib compared to that of olaparib alone (Phase II) [ Time Frame: The duration of time from start of treatment to time of objective disease progression, assessed up to 3 years ] [ Designated as safety issue: No ]Will be evaluated by Kaplan-Meier analysis and log-rank test for between group comparison, and median survival times reported.
- Toxicities of the combination of cediranib maleate and olaparib (Phase I) [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
- Tumor response rate (Phase II) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
- Clinical benefit rate defined as response or stable disease x 16 weeks, as determined by RECIST 1.1 criteria (Phase II) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
- Overall survival (Phase II) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]Will also be evaluated by Kaplan-Meier analysis and log-rank test for between-group comparison, and median survival time will be reported.
|Study Start Date:||March 2010|
|Estimated Primary Completion Date:||May 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm I (cediranib maleate and olaparib)
Patients receive cediranib maleate PO once daily and olaparib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other Names:Drug: cediranib maleate
Other Names:Other: laboratory biomarker analysis
Experimental: Arm II (olaparib)
Patients receive olaparib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other Names:Other: laboratory biomarker analysis
Hide Detailed Description
I. Assess the maximum tolerated dose (MTD) of cediranib (cediranib maleate) in combination with olaparib in the treatment of recurrent ovarian, fallopian tube, or peritoneal cancer or metastatic triple-negative breast cancer. (Phase I) II. Assess the efficacy (as measured by progression-free survival [PFS]) of the combination of cediranib and olaparib compared to olaparib alone in recurrent grade 2 or 3 platinum-sensitive papillary-serous or endometrioid ovarian, fallopian tube, or peritoneal cancer. (Phase II)
I. Assess the toxicities of the combination of cediranib and olaparib in the treatment of recurrent ovarian, fallopian tube, or peritoneal cancer or metastatic triple-negative breast cancer. (Phase I) II. Assess clinical benefit, progression-free survival, and overall survival for patients treated with cediranib and olaparib. (Phase I) III. Assess tumor response, clinical response benefit (response or stable disease as defined by Response Evaluation Criteria in Solid Tumors [RECIST] response criteria x 16 weeks), and overall survival (OS) for patients treated with cediranib and olaparib at the recommended phase II dose (RP2D) as compared with patients receiving olaparib alone. (Phase II)
I. To evaluate the prognostic and predictive role of measured changes in functional vascular imaging using delayed contrast-enhanced (DCE)-magnetic resonance imaging (MRI) between pre-study and day 3. (Phase II) II. To evaluate in an exploratory fashion the predictive or prognostic value of single nucleotide polymorphisms (SNPs) in key genes involved in angiogenesis and deoxyribonucleic acid (DNA) repair. (Phase II) III. To evaluate the predictive value of baseline peripheral blood mononuclear cells (PBMC) polyadenine diphosphate (ADP) ribose (PAR) incorporation on response to therapy. (Phase II) IV. To measure early changes in vascular cytokine production and evaluate in an exploratory fashion that these changes may be predictive or prognostic, or differentially affected by the combination of agents. (Phase II) V. To evaluate early changes to circulating endothelial cells and if these changes are predictive or prognostic. (Phase II) VI. To assess changes in measures of DNA damage and repair and angiogenesis in tumor cells (tissue and/or malignant effusions) and correlate to drug/drug/combination. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of cediranib maleate and olaparib followed by a randomized phase II study.
ARM I: Patients receive cediranib maleate orally (PO) once daily and olaparib PO twice daily (BID) on days 1-28.
ARM II: Patients receive olaparib PO BID on days 1-28.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for up to 3 years.
In the first part of the study, since we were looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects, not everyone who participated in this part of the research study received the same dose of the study drug. This portion of the study has now completed.
In the second portion of the study, participants will be randomized to receive either the combination of cediranib maleate and olaparib or to receive olaparib alone. Participants will know which arm they have been randomized to, but do not have any control over which arm it will be.
Each cycle lasts four weeks (28 days), and participants will be taking the study drugs for the entire four weeks. Participants will take drugs orally as specified in the given treatment arm. Cediranib maleate tablets will be taken once in the morning and olaparib capsules will be taken twice a day.
Participants will be asked to monitor their blood pressure on a twice daily basis at home and keep a blood pressure diary. The following tests and procedures will be performed at specific time intervals while the participant is on the study: physical exam, vital signs, blood tests, computed tomography (CT) scan/MRI, urine test and electrocardiogram (ECG).
|United States, California|
|Cedars-Sinai Medical Center|
|Los Angeles, California, United States, 90048|
|United States, Illinois|
|University of Chicago Comprehensive Cancer Center|
|Chicago, Illinois, United States, 60637-1470|
|Kellogg Cancer Center - Evanston Hospital|
|Evanston, Illinois, United States, 60201|
|United States, Indiana|
|Fort Wayne Medical Oncology and Hematology Inc - State Boulevard|
|Fort Wayne, Indiana, United States, 46845|
|United States, Maryland|
|Johns Hopkins University|
|Baltimore, Maryland, United States, 21287-8936|
|National Cancer Institute|
|Rockville, Maryland, United States, 20850|
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|Massachusetts General Hospital Cancer Center|
|Boston, Massachusetts, United States, 02114|
|Newton, Massachusetts, United States, 02462|
|United States, Michigan|
|University of Michigan|
|Ann Arbor, Michigan, United States, 48109|
|Principal Investigator:||Joyce Liu||Dana-Farber Cancer Institute|