NCT06654037

Testing the Addition of an Anti-Cancer Drug, Abemaciclib, to the Usual Chemotherapy Treatment (5-Fluorouracil) for Metastatic, Refractory Colorectal Cancer

A Phase 1 Study of 5-Fluorouracil in Combination With Abemaciclib in Metastatic, Refractory CRC

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 39 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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 (PK) of abemaciclib and 5-FU. EXPLORATORY OBJECTIVES: I. To explore exposure-response relationships for abemaciclib and 5-FU. II. To evaluate circulating tumor DNA (ctDNA) as a predictor for treatment response to therapy. OUTLINE: This is a dose-escalation study of abemaciclib in combination with 5-FU followed by a dose-expansion study. Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-28 and 5-FU intravenously (IV) over 46 hours on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and radiologic imaging throughout the study and may additionally undergo a tissue biopsy before treatment and on cycle 1 day 16. After completion of study treatment, patients are followed up every 3 months for 6 months.

Conditions

• Metastatic Microsatellite Stable Colorectal Carcinoma
• Refractory Microsatellite Stable Colorectal Carcinoma
• Stage IV Colorectal Cancer AJCC v8

Interventions

Type	Name	Description
DRUG	Abemaciclib	Given PO
PROCEDURE	Biopsy Procedure	Undergo tissue biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
DRUG	Fluorouracil	Given IV
PROCEDURE	Radiologic Imaging Procedure	Undergo radiologic imaging

Timeline

• Start date: 2025-04-18
• Primary completion: 2027-04-01
• Completion: 2027-04-01
• First posted: 2024-10-23
• Last updated: 2026-04-14

Locations

8 sites across 1 country: United States

Regulatory

• FDA-regulated drug study