A Phase 1 Study of 5-Fluorouracil in Combination With Abemaciclib in Metastatic, Refractory CRC
National Cancer Institute (NCI)
Summary
This phase I trial tests the safety, side effects, and best dose of abemaciclib in combination with 5-fluorouracil and how well it works in treating patients with colorectal cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and that has not responded to treatment (refractory). Abemaciclib, a type of cyclin-dependent kinase inhibitor, blocks certain proteins, which may help keep tumor cells from growing. 5-fluorouracil, a type of antimetabolite, stops cells from making deoxyribonucleic acid (DNA) and may kill tumor cells. Giving abemaciclib in combination with 5-fluorouracil may be safe, tolerable, and/or effective in treating patients with metastatic and refractory colorectal cancer.
Description
PRIMARY OBJECTIVE: I. To determine the safety and tolerability, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of abemaciclib in combination with 5-fluorouracil (5-FU) in patients with colorectal cancer (CRC). SECONDARY OBJECTIVES: I. To estimate the anti-tumor activity of abemaciclib in combination with 5-FU. II. To determine the pharmacodynamics (PD) of abemaciclib in combination with 5-FU (death receptor 5 \[DR5\] dynamics and apoptosis). III. To identify molecular subpopulations particularly sensitized to abemaciclib and 5-FU. IV. To determine the pharmacokinetics (P…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Patients must have histologically or cytologically confirmed microsatellite stability (MSS) metastatic colorectal cancer where patients have progressed on standard therapies which would have included 5-FU or capecitabine, oxaliplatin, and irinotecan. Patients must have had progression of disease (PD) or intolerance to bevacizumab and anti-EGFR antibodies (cetuximab or panitumumab) in patients who have left-sided and RAS-wildtype CRC * Patients must have measurable disease * Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of abem…
Interventions
- DrugAbemaciclib
Given PO
- ProcedureBiopsy Procedure
Undergo tissue biopsy
- ProcedureBiospecimen Collection
Undergo blood sample collection
- DrugFluorouracil
Given IV
- ProcedureRadiologic Imaging Procedure
Undergo radiologic imaging
Locations (8)
- UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory CareIrvine, California
- UC Irvine Health/Chao Family Comprehensive Cancer CenterOrange, California
- Montefiore Medical Center-Einstein CampusThe Bronx, New York
- Montefiore Medical Center-Weiler HospitalThe Bronx, New York
- Montefiore Medical Center - Moses CampusThe Bronx, New York
- University of Cincinnati Cancer Center-UC Medical CenterCincinnati, Ohio