A Randomized Trial of Selumetinib and Olaparib or Selumetinib Alone in Patients With Recurrent or Persistent RAS Pathway Mutant Ovarian and Endometrial Cancers: A ComboMATCH Treatment Trial
National Cancer Institute (NCI)
Summary
This phase II ComboMATCH treatment trial compares selumetinib plus olaparib to selumetinib alone in women with endometrial or ovarian (fallopian tube and primary peritoneal) cancer that has come back (recurrent) or that remains despite treatment (persistent) and harbors a mutation in the RAS pathway. Selumetinib 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. The addition of olaparib to selumetinib could increase the percentage of tumors that shrink as well as lengthen the time that the tumors remain stable (without progression) as compared to selumetinib alone.
Description
PRIMARY OBJECTIVES: I. Compare progression free survival of combination of olaparib and selumetinib sulfate (selumetinib) to selumetinib alone in patients with RAS mutant ovarian cancer. (Cohort 1) II. Compare progression free survival of combination of olaparib and selumetinib to selumetinib alone in patients with RAS mutant endometrial cancer. (Cohort 2) SECONDARY OBJECTIVES: I. Determine safety of both arms per Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. II. Compare objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 between t…
Eligibility
- Age range
- 18+ years
- Sex
- Female
- Healthy volunteers
- No
Inclusion Criteria: * Patient must have enrolled onto EAY191 and must have been given a treatment assignment to ComboMATCH to EAY191-N4 based on the presence of an actionable mutation as defined in EAY191 * Patients must be enrolled on the ComboMATCH Master Registration Trial EAY191 * Patients must have RAS pathway mutations as determined by the ComboMATCH screening assessment * Cohort 1: Patients with histologically confirmed RAS pathway mutant ovarian, primary peritoneal, or fallopian tube ("ovarian") cancer (activating mutations in KRAS, NRAS, HRAS, BRAF, MEK1, MEK2, or inactivating mut…
Interventions
- ProcedureBiopsy Procedure
Undergo tumor biopsy
- ProcedureBiospecimen Collection
Undergo blood collection
- ProcedureBone Marrow Aspiration and Biopsy
Undergo bone marrow aspiration or biopsy
- ProcedureComputed Tomography
Undergo CT scan
- ProcedureEchocardiography Test
Undergo ECHO
- ProcedureMultigated Acquisition Scan
Undergo MUGA
- DrugOlaparib
Locations (296)
- University of Alabama at Birmingham Cancer CenterBirmingham, Alabama
- University of South Alabama Mitchell Cancer InstituteMobile, Alabama
- Alaska Women's Cancer CareAnchorage, Alaska
- CTCA at Western Regional Medical CenterGoodyear, Arizona
- Kingman Regional Medical CenterKingman, Arizona
- PCR OncologyArroyo Grande, California