Cediranib Maleate and Olaparib in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery
This phase II trial studies cediranib maleate in combination with olaparib in treating patients with solid tumors that have spread to other parts of the body or cannot be removed by surgery, including breast cancer, non-small cell lung cancer, small cell lung cancer, and pancreatic cancer. Cediranib maleate and olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Cediranib maleate may also block the flow of oxygen to the tumor, and may help make the tumor more sensitive to olaparib.
Estrogen Receptor Negative
Metastatic Pancreatic Adenocarcinoma
Progesterone Receptor Negative
Recurrent Breast Carcinoma
Recurrent Non-Small Cell Lung Carcinoma
Recurrent Pancreatic Carcinoma
Recurrent Small Cell Lung Carcinoma
Stage III Pancreatic Cancer
Stage IIIA Breast Cancer
Stage IIIA Non-Small Cell Lung Cancer
Stage IIIA Small Cell Lung Carcinoma
Stage IIIB Non-Small Cell Lung Cancer
Stage IIIB Small Cell Lung Carcinoma
Stage IIIC Breast Cancer
Stage IV Breast Cancer
Stage IV Non-Small Cell Lung Cancer
Stage IV Small Cell Lung Carcinoma
Stage IVA Pancreatic Cancer
Stage IVB Pancreatic Cancer
Triple-Negative Breast Carcinoma
Drug: Cediranib Maleate
Other: Laboratory Biomarker Analysis
Procedure: Positron Emission Tomography
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Study of Cediranib in Combination With Olaparib in Advanced Solid Tumors|
- ORR, measured by RECIST v 1.1 [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: No ]The exact two-sided 95% confidence interval for the ORR will be reported.
- Incidence of toxicity, graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: Yes ]Adverse medical events will be tabulated. NCI toxicity grade 3 and grade 4 laboratory abnormalities will be listed.
- PFS [ Time Frame: The duration of time from start of treatment to time of progression or death, whichever occurs first, assessed up to 4 weeks after completion of study treatment ] [ Designated as safety issue: No ]Estimated using the Kaplan-Meier method with the 95% confidence intervals (CIs). The Rothman CI, CI based on the Greenwoods variance, Thomas and Grunkemeier CI and the simultaneous confidence bands by Nair and Hall and Wellner will be reported. The possible risk factors will be compared for survival with log-rank test. For multivariate analysis, the proportional hazards Cox model will be applied to investigate potential prognostic factors, such as age and stage of disease on the survival data. The adjusted p-values of the hazard ratios and the adjusted 95% confidence interval will be reported.
- Biomarker data [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: No ]The biomarker data analysis including miRNAs data will be completed using the Lasso based elastic net method. The penalty parameter that controls the shrinkage of fixed terms and the variable selection will be determined by k-fold cross validation. Due to the limited sample size, the biomarker data analysis is for the exploratory research only.
- PET imaging data [ Time Frame: Up to day 4 ] [ Designated as safety issue: No ]The general non-linear and generalized non-liner model will be used to analyze PET imaging data.
|Study Start Date:||January 2016|
|Estimated Primary Completion Date:||June 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (cediranib maleate, olaparib)
Patients receive cediranib maleate PO QD for 3-4 days and then undergo biopsy. After biopsy, patients continue to receive cediranib maleate PO QD and begin olaparib PO BID on the day after the post-dose biopsy (day 4-7) or by day 8 of course 1 (biopsy cohorts-NSCLC and TNBC) or day 4 of course 1 (non-biopsy cohorts-PDAC and SCLC). Courses repeat every 28 days (35 days for course 1) in the absence of disease progression or unacceptable toxicity.
Other Names:Drug: Cediranib Maleate
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Olaparib
Other Names:Procedure: Positron Emission Tomography
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT02498613
|United States, Connecticut|
|Yale University Cancer Center LAO||Not yet recruiting|
|New Haven, Connecticut, United States, 06520|
|Contact: Joseph W. Kim 203-737-6467 email@example.com|
|Principal Investigator: Joseph W. Kim|
|Principal Investigator:||Joseph Kim||Yale University Cancer Center LAO|