A Phase 1B Study of Combination ATR (M1774) and BET Inhibition (ZEN003694) to Exploit ARID1A Loss in Recurrent Ovarian and Endometrial Cancer
National Cancer Institute (NCI)
Summary
This phase Ib trial tests the safety, side effects, and best dose of M1774 when given with ZEN-3694 in treating patients with ovarian and endometrial cancer that has come back (recurrent). M1774 and ZEN-3694 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. M1774 and ZEN-3694 combined together has demonstrated to be better than either drug alone in killing ovarian tumor cells.
Description
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) for combination of tuvusertib (ATR inhibitor \[M1774\]) and BET bromodomain inhibitor ZEN-3694 (BET inhibitor \[ZEN003694\]) in women with recurrent clear cell, endometrioid, and platinum resistant high grade serous ovarian carcinoma (HGSOC) and clear cell and endometrioid endometrial carcinoma irrespective of ARID1A status (PART I). II. To determine safety and tolerability in ARID1A pathogenic alteration (ARID1A\^MUTATION \[MUT\]) and ARID1A wildtype (ARID1A\^WT) cohorts (ARID1A is a…
Eligibility
- Age range
- 18+ years
- Sex
- Female
- Healthy volunteers
- No
Inclusion Criteria: * Patients must have pathologically confirmed: * PART I: Recurrent clear cell or endometrioid ovarian carcinoma (at least 50% morphology of clear cell and endometrioid required), recurrent clear cell and low grade endometrioid endometrial carcinoma (The International Federation of Gynecology and Obstetrics \[FIGO\] grade 1), or recurrent platinum resistant high grade serous ovarian carcinoma * NOTE: platinum-resistant disease is defined as progression within \< 6 months from completion of platinum-based therapy. The date should be calculated from the last administered…
Interventions
- DrugBET Bromodomain Inhibitor ZEN-3694
Given PO
- ProcedureBiopsy Procedure
Undergo biopsy
- ProcedureBiospecimen Collection
Undergo collection of blood samples
- ProcedureComputed Tomography
Undergo CT
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- DrugTuvusertib
Given PO
- ProcedureX-Ray Imaging
Undergo x-ray
Locations (14)
- Augusta University Medical CenterAugusta, Georgia
- University of Chicago Comprehensive Cancer CenterChicago, Illinois
- University of Iowa/Holden Comprehensive Cancer CenterIowa City, Iowa
- Wayne State University/Karmanos Cancer InstituteDetroit, Michigan
- University of New Mexico Cancer CenterAlbuquerque, New Mexico
- Case Western Reserve UniversityCleveland, Ohio