EAY191-N4: A Randomized Trial of Selumetinib and Olaparib or Selumetinib Alone in Patients With Recurrent or Persistent RAS Pathway Mutant Ovarian and Endometrial Cancers
About
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 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.
Arm 1: selumetinib 75mg + olaparib 300mg taken orally twice daily
Arm 2: selumetinib 75mg taken orally twice daily
Eligibility Criteria
Inclusion Criteria
- Must be enrolled on the ComboMATCH Master Registration Trial EAY191
- Cohort 1: Must have histologically confirmed RAS pathway mutant ovarian, primary peritoneal or fallopian tube (“ovarian”) cancer (activating mutations in KRAS, NRAS, HRAS, BRAF, MEK1, MEK2 or inactivating mutations in NF1)
- Cohort 2: Must have histologically confirmed RAS pathway mutant endometrial cancer (activating mutations in KRAS, NRAS, HRAS, BRAF, MEK1, MEK2 or inactivating mutations in NF1)
- Must have progressed after first-line treatment for recurrent or persistent disease and may have received unlimited prior therapy
- Ovarian cancer: should not be eligible for further platinum-based therapy
- Endometrial cancer: must have received or been offered an immune oncology agent (alone or in combination with lenvatinib) unless there are existing contraindications for immune oncology agents or lenvatinib
- Must have measurable (defined by RECIST 1.1) and biopsiable disease
- Patients with known history or current symptoms of cardiac disease must have NYHA functional classification class 2B or better
Exclusion Criteria
- Prior use of MEK inhibitors or progression while receiving a PARP inhibitor
- ≥ Grade 2 neuropathy within 14 days of registration or severe (Child-Pugh C) liver dysfunction
- Prior use of CYP3A and CYP2C19 inhibitors or CYP3A inducers
- Known MDS/AML or with features suggestive of MDS/AML, or ophthalmological conditions
- Prior organ transplant, allogenic bone marrow transplant or double umbilical cord blood transplantation, or whole blood transfusion within 28 days prior to registration
- History of confirmed pneumonitis, uncontrolled hypertension (BP ≥ 150/90 mmHg), acute coronary syndrome within 6 months prior to registration, uncontrolled atrial fibrillation or known family history of long QT syndrome
Primary Investigator
Erin J. Saks is a board-certified gynecologic oncologist. She completed her residency at Brown University Alpert Medical School and Gynecologic Oncology fellowship at the University of Virginia. Dr. Saks joined the faculty of the Department of Obstetrics and Gynecology in 2018 and is an assistant professor at the Virginia Tech Carilion School of Medicine.
Contact Information
Katie Church, MS, MA
Clinical Research Coordinator
