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

NCT06654037 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: NCI-2024-0869110670UM1CA186690
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• Dose-limiting toxicity (DLT)

  Will be tabulated using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 for each dose level.

  Within first cycle (cycle length = 28 days)

• Maximum tolerated dose (MTD)

  MTD will be the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate.

  Up to completion of dose-escalation phase

• Incidence of adverse events

  Will be evaluated using CTCAE v 5.0 and will be tabulated for each dose level.

  Up to 30 days after last dose of study treatment

Secondary Outcomes (8)

• Objective response rate (ORR)

  Up to 6 months post-treatment

• Clinical benefit rate

  Up to 6 months post-treatment

• Progression free survival (PFS)

  From the start of treatment to time of progression or death, assessed up to 6 months post-treatment

• Ribonucleic acid sequencing of death receptor 5

  At pre-treatment on cycle 1 day 16

• Apoptosis by Pharmacodynamics Assay Development & Implementation Section lab

  At pre-treatment cycle 1 day 16

Other Outcomes (2)

• Abemaciclib AUC and trough levels 5-FU AUC

  At cycle1 day 1 pre-dose and cycle 1 day 2 (22-26 hours post start of 5-FU infusion)

• Change in variant allele frequencies (VAF) of tumor mutations in circulating tumor DNA

  At baseline and at start of cycle 3 (cycle length = 28 days)

Study Arms (1)

Treatment (abemaciclib, 5-FU)

EXPERIMENTAL

Patients receive abemaciclib PO BID on days 1-28 and 5-FU 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.

Drug: Abemaciclib; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Fluorouracil; Procedure: Radiologic Imaging Procedure

Interventions

Radiologic Imaging Procedure PROCEDURE

Undergo radiologic imaging

Treatment (abemaciclib, 5-FU)

Abemaciclib DRUG

Given PO

Also known as: LY 2835219, LY-2835219, LY2835219, Verzenio

Treatment (abemaciclib, 5-FU)

Biopsy Procedure PROCEDURE

Undergo tissue biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (abemaciclib, 5-FU)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (abemaciclib, 5-FU)

Fluorouracil DRUG

Given IV

Also known as: 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-Fu, 5FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Treatment (abemaciclib, 5-FU)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 abemaciclib in combination with 5-FU in patients \< 18 years of age, children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
• Hemoglobin ≥ 8 g/dL
• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN for patients who do not have liver metastases, and ≤ 5 x institutional ULN for patients with liver metastases
• Glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m\^2
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

You may not qualify if:

• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia or grade 2 peripheral neuropathy. Patients who are experiencing immune related adverse events (AEs) which are adequately treated with hormone replacement therapy, including diabetes on insulin regimen, hypothyroidism on levothyroxine, and adrenal insufficiency on steroid replacement will also be eligible
• Patients who are receiving any other investigational agents. There is to be a washout period of two weeks or five half-lives, whichever is shorter, for all investigational agents prior to treatment initiation on this study. Individual cases can be discussed with the national PI
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to abemaciclib or other agents (5-FU) used in study such as a previous intolerance to 5-FU or capecitabine, including patients with known or suspected dihydropyrimidine dehydrogenase deficiency
• Patients who have received previous treatment with a CDK4/6 inhibitor
• Patients with a gastrointestinal pathology or history that adversely impacts the ability to take or absorb oral medication
• Patients with peritoneal metastases complicated by ascites which are refractory to diuretic therapy and requires therapeutic paracenteses more than once every 2 weeks
• Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A enzymes before enrollment or while on protocol therapy are ineligible. Patients receiving moderate CYP3A inhibitors or inducers will be monitored. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
• Pregnant women are excluded from this study because abemaciclib is a CDK-inhibiting agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with abemaciclib, breastfeeding should be discontinued if the mother is treated with abemaciclib. These potential risks may also apply to other agents used in this study

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (8)

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California, 92612, United States

RECRUITING

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

RECRUITING

Montefiore Medical Center-Einstein Campus

The Bronx, New York, 10461, United States

RECRUITING

Montefiore Medical Center-Weiler Hospital

The Bronx, New York, 10461, United States

RECRUITING

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467, United States

RECRUITING

University of Cincinnati Cancer Center-UC Medical Center

Cincinnati, Ohio, 45219, United States

RECRUITING

University of Cincinnati Cancer Center-West Chester

West Chester, Ohio, 45069, United States

RECRUITING

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

abemaciclib; Biopsy; Specimen Handling; Fluorouracil; dehydroftorafur

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Janie Y Zhang

  UPMC Hillman Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2024
• First Posted: October 23, 2024
• Study Start: April 18, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (8)