A Phase 1/1b Dose Escalation Study of Abemaciclib and Olaparib for Recurrent Platinum-Resistant Ovarian Cancer
National Cancer Institute (NCI)
Summary
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.
Description
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 transc…
Eligibility
- Age range
- 18+ years
- Sex
- Female
- Healthy volunteers
- No
Inclusion Criteria: * Patients must have histologically confirmed recurrent platinum-resistant epithelial ovarian carcinoma (EOC) of any histology, as defined by progression within 6 months of the last dose of platinum-based chemotherapy. Both primary platinum resistant and acquired platinum resistant patients are allowed * High-grade serous histology is required (for the dose expansion cohort only) (data on BRCA (e.g. germline BRCA, Somatic BRCA, Neither, Unknown) and homologous recombination deficiency (HRD)/Loss of Heterozygosity (LOH) (e.g. HRD \> 42/LOH \>16%, HRD score \< 42/LOH \< 16%,…
Interventions
- DrugAbemaciclib
Given PO
- ProcedureBiopsy Procedure
Undergo tumor biopsy
- ProcedureBiospecimen Collection
Undergo collection of blood
- DrugOlaparib
Given PO
Locations (27)
- Mayo Clinic Hospital in ArizonaPhoenix, Arizona
- UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory CareIrvine, California
- Los Angeles General Medical CenterLos Angeles, California
- USC / Norris Comprehensive Cancer CenterLos Angeles, California
- UC Irvine Health/Chao Family Comprehensive Cancer CenterOrange, California
- UM Sylvester Comprehensive Cancer Center at Coral GablesCoral Gables, Florida