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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.
I. To determine the objective response rate (ORR) of cediranib (cediranib maleate) plus olaparib in combination in patients with advanced or metastatic solid tumors of the following tumor types: non-small cell lung cancer (NSCLC), germline breast cancer, early onset 1/2 (BRCA1/2) wild type (wt) triple negative breast cancer (TNBC), pancreatic ductal adenocarcinoma (PDAC), and small cell lung cancer (SCLC). The responses will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
I. To assess the safety and tolerability of oral administration of cediranib in combination with olaparib in patients with select advanced solid tumors.
II. To determine progression free survival (PFS) in each tumor cohort.
I. In the NSCLC cohort of the study, to determine changes in tumor hypoxia on cediranib treatment compared to baseline by positron emission tomography (PET) imaging using [F-18] fluoromisonidazole (F-MISO) as a tracer.
II. To correlate ORR with hypoxia levels at baseline and changes from baseline. III. To determine in tumor tissue, if the BRCA1 gene is repressed or silenced by cediranib treatment and correlate with ORR.
IV. To determine changes in other markers of hypoxia in tumor tissue, correlate with BRCA1 expression and ORR.
V. To correlate hypoxia levels determined by PET imaging with BRCA1 gene expression and hypoxia markers.
VI. To determine baseline levels and changes in angiogenesis markers in plasma, including plasma vascular endothelial growth factor (VEGF) and correlate with ORR and other correlative markers in patients where tissue is available as well as hypoxia levels measured by PET imaging.
VII. To determine changes in microribonucleic acids (miRNAs) related to hypoxia and correlate with ORR and other correlative markers in patients where tissue is available as well as hypoxia levels determined by PET imaging.
VIII. To assess gene variants and mutations in tumors (NSCLC and breast cancer [BC] cohorts) using the BROCA panel to explore, if any variants in genes involved in deoxyribonucleic acid (DNA) damage repair or hypoxia pathways predict ORR and explore correlation with any of the other biomarkers measured in the study.
Patients receive cediranib maleate orally (PO) once daily (QD) for 3-4 days and then undergo biopsy. After biopsy, patients continue to receive cediranib maleate PO QD and begin olaparib PO twice daily (BID) beginning on the day after the post-dose biopsy (days 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.
After completion of study treatment, patients are followed up for 4 weeks.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Estrogen Receptor Negative
18F-Fluoromisonidazole, Cediranib Maleate, Laboratory Biomarker Analysis, Olaparib, Positron Emission Tomography
Yale University Cancer Center LAO
Not yet recruiting
National Cancer Institute (NCI)
Published on BioPortfolio: 2015-07-16T11:08:23-0400
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