Recurrent Platinum-Resistant Ovarian Carcinoma Clinical Trial
Official title:
A Phase 1/1b Dose Escalation Study of Abemaciclib and Olaparib for Recurrent Platinum-Resistant Ovarian Cancer
This phase I/Ib trial identifies the side effects and best dose of abemaciclib when given together with olaparib in treating patients with ovarian cancer that responds at first to treatment with drugs that contain the metal platinum but then comes back within a certain period (recurrent platinum-resistant). Abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep tumor cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Adding abemaciclib to olaparib may work better to treat recurrent platinum-resistant ovarian cancer.
PRIMARY OBJECTIVE: I. To assess the safety of abemaciclib plus olaparib in patients with platinum-resistant ovarian cancer by determining the maximum tolerated dose and recommended phase 2 dose. SECONDARY OBJECTIVE: I. To observe and record anti-tumor activity using overall response rate (ORR) and duration of response (DoR) with abemaciclib and olaparib, given in combination, in patients with platinum-resistant ovarian cancer. EXPLORATORY OBJECTIVES: I. To assess proof of mechanism (RB, phosphoRB, cleaved caspase 3, Ki67, geminin, gamma-H2AX, RAD51 nuclear foci, pNBS multiplex, Myc transcriptional targets ODC1 and LDHA, homologous recombination genes BRCA1, BRCA2, RAD51, serum thymidine kinase), plasma and tumor pharmacokinetics, and subgroups of response (immunohistochemistry [IHC] for Myc, cyclin E; next generation sequencing [NGS]/whole exome sequencing [WES] for DCAF, hormone receptor [HR] repair gene alterations, Myc, and CCNE1; ribonucleic acid sequencing [RNAseq] for Myc and CCNE1). II. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data, including presentation, diagnosis, staging, summary treatment, and if possible, outcome. III. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood (for cell-free DNA analysis), and nucleic acids obtained from patients at the Experimental Therapeutics Clinical Trials Network (EET) Biobank at Nationwide Children's Hospital. OUTLINE: This is a dose-escalation study of abemaciclib. Patients receive olaparib orally (PO) twice daily (BID) on days 1-28 and abemaciclib PO BID on days 8-28 of cycle 1 and days 1-28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and undergo tumor biopsy on study. After completion of study treatment, patients are followed up at 30 days. ;
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