Trial of 5-Fluorouracil (5FU)-Based Therapy in Combination With Fruquintinib in Patients With Locally Advanced Unresectable or Metastatic Colorectal Cancer

NCT07042685 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PRO00039815 (HMCC-GI25-001)
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase II clinical trial at Houston Methodist Neal Cancer Center is evaluating the safety and efficacy of combining 5-Fluorouracil (5FU) -based chemotherapy (either FOLFIRI: folinic acid, 5FU, irinotecan; or mFOLFOX6: folinic acid, 5FU, oxaliplatin) with fruquintinib as a first-line treatment for patients with locally advanced unresectable or metastatic colorectal cancer. Fifty patients will receive treatment in 28-day cycles, with fruquintinib initially dosed at 4 mg daily and potentially increased to 5 mg if no significant toxicities are observed. After six months, patients showing stable disease or better will transition to a maintenance phase with 5FU and fruquintinib, continuing until disease progression or other discontinuation criteria are met. The primary endpoint is time to progression based on RECIST v1.1 criteria, while secondary endpoints include safety, tolerability, and duration of response. The trial is being conducted across multiple Houston Methodist hospitals and is currently the only first-line CRC trial available in the system. If successful, it could offer a new therapeutic option and inform future treatment guidelines for advanced colorectal cancer.

Conditions

Metastatic Colorectal Cancer (CRC)

Keywords

first line; CRC; metastatic

Outcome Measures

Primary Outcomes (1)

• Time to Progression of 5FU in combination with fruquintinib in first-line metastatic colorectal cancer patients

  To assess the time to progression (TTP) of patients with locally advanced unresectable or metastatic colorectal cancer (mCRC) treated with 5-Fluorouracil (5FU)-based therapy in combination with fruquintinib, according to RECIST v1.1 criteria.

  From date of initial treatment until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws, whichever comes first, assessed up to 24 months.

Secondary Outcomes (2)

• Incidence of toxicity of 5FU in combination with fruquintinib in first-line metastatic colorectal cancer patients

  From date of initial treatment until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws from the study, whichever came first, assessed up to 13 months.

• Duration of the response of 5FU in combination with fruquintinib in first-line metastatic colorectal cancer patients

  From date of initial treatment until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws, whichever comes first, assessed up to 24 months.

Other Outcomes (4)

• Overall Survival rate of first-line metastatic colorectal cancer patients with 5FU in combination with fruquintinib

  From date of initial treatment, 6 and 12 months, assessed up to 24 months until death.

• Overall Response Rate of first-line metastatic colorectal cancer patients with 5FU in combination with fruquintinib

  From date of initial treatment until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws, whichever comes first, assessed up to 24 months.

• Changes in health-related quality of life for first-line metastatic colorectal cancer patients with 5FU in combination with fruquintinib

  From baseline to months 6 and 12

Study Arms (1)

5FU-based chemotherapy (FOLFIRI or mFOLFOX6) with fruquintinib

EXPERIMENTAL

The trial includes a single treatment arm in which all enrolled patients receive a combination of 5-Fluorouracil (5FU)-based chemotherapy and fruquintinib. Patients are treated with either the FOLFIRI or mFOLFOX6 (FOLFIRI: folinic acid, 5FU, irinotecan; or mFOLFOX6: folinic acid, 5FU, oxaliplatin) regimen, both of which include 5-fluorouracil (5FU), leucovorin (LV), and either irinotecan or oxaliplatin, respectively. Fruquintinib is administered orally once daily for 21 days of each 28-day cycle. The initial three patients receive 4 mg of fruquintinib daily to assess safety; if no dose-limiting toxicities are observed, the dose is increased to 5 mg for subsequent patients. Treatment continues until disease progression, unacceptable toxicity, or patient withdrawal. After six months, patients with stable disease or better transition to a maintenance phase with 5FU and fruquintinib alone.

Drug: Fruquintinib Combined With Chemotherapy

Interventions

Fruquintinib Combined With Chemotherapy DRUG

The intervention in this trial involves administering a combination of 5FU-based chemotherapy and fruquintinib to patients with locally advanced unresectable or metastatic colorectal cancer. Patients receive either the FOLFIRI or mFOLFOX6 regimen, both of which include 5-fluorouracil (5FU), leucovorin (LV), and either irinotecan (FOLFIRI) or oxaliplatin (mFOLFOX6). Fruquintinib is given orally once daily for 21 days in each 28-day cycle. The initial dose of fruquintinib is 4 mg daily for the first three patients to assess safety; if no dose-limiting toxicities are observed, the dose is increased to 5 mg daily for subsequent participants. Treatment continues until disease progression, unacceptable toxicity, or patient withdrawal. After six months, patients with stable disease or better transition to a maintenance phase with 5FU and fruquintinib alone.

Also known as: Fruquintinib

5FU-based chemotherapy (FOLFIRI or mFOLFOX6) with fruquintinib

Eligibility Criteria

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

You may qualify if:

• Male or female ≥18 years of age.
• Written informed consent is required before performing any trial-specific tests or procedures. Signing of the informed consent form can occur outside the 28-day screening period.
• Histopathologically or cytologically confirmed locally advanced unresectable or metastatic colorectal cancer. The study will include an all-comer population, meaning that patients will not be excluded based on specific molecular markers such as microsatellite instability-high (MSI-H) or B-Raf proto-oncogene mutations (BRAF mutations). However, as part of the Standard of Care, comprehensive molecular testing will be performed to assess MSI status, and other relevant biomarkers. For patients with MSI-H or BRAF mutations confirmed, treatment may be adjusted per Standard of Care practices.
• Measurable disease per RECISTv1.1.
• No prior systemic treatment. Patients with resected disease who later develop unresectable recurrence without prior systemic therapy remain eligible.
• ECOG performance status of 0 or 1.
• Life expectancy ≥6 months per treating physician's assessment.
• Patients of childbearing potential must agree to use an adequate method of contraception during the study and for 30 days after the last dose of study treatment.
• Patients must be able to swallow oral tablets.

You may not qualify if:

• Hematology laboratory values of:
• Absolute neutrophil count ≤1500 cells/mm3
• Platelets ≤100,000 cells/mm3
• Hemoglobin ≤9 g/dL
• White blood count ≤3000 cells/mm3.
• Hepatic laboratory values of aspartate transaminase (AST) or alanine aminotransferase (ALT):
• \>5 × upper limits of normal (ULN) if the documented history of hepatic metastases; or
• \>2.5 × ULN if no liver metastases are present.
• Serum albumin \<2.8 g/dL.
• Total bilirubin \>1.7 mg/dL × ULN.
• Prothrombin time (PT) or international normalized ratio (INR) \>1.5 × ULN. Note: Patients receiving therapeutic doses of anticoagulant therapy may be considered eligible if PT and INR are within the acceptable institutional therapeutic limits.
• Serum creatinine or serum urea \>1.5 × ULN.
• Estimated glomerular filtration rate \<50 mL/min.
• Urine dipstick or urinalysis with protein ≥2+ or 24-hour urine protein ≥1.0 g/24-h. Subjects with 1+ proteinuria must undergo a 24-hour urine collection to assess urine protein level.
• Positive pregnancy test, pregnant, or breastfeeding for all women of child-bearing potential.

Sponsors & Collaborators

• Takeda Development Center Americas, Inc.: collaborator
• The Methodist Hospital Research Institute: lead

Study Sites (1)

Houston Methodist Neal Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Publications (16)

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MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis

Interventions

Drug Therapy; HMPL-013

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Maen Abdelrahim, MD, PhD, Pharm D

  The Methodist Hospital Research Institute

  PRINCIPAL INVESTIGATOR

• Abdullah Esmail, MD

  Houston Methodist Neal Cancer Center

  STUDY DIRECTOR

Central Study Contacts

Safiya Joseph

CONTACT

3462382420; sdjoseph@houstonmethodist.org

Titilayo Olubajo

CONTACT

7133639803; tolubajo@houstonmethodist.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2025
• First Posted: June 29, 2025
• Study Start: January 27, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR

Locations

US (1)