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.
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.
Absolute neutrophil count ≤1500 cells/mm3
Platelets ≤100,000 cells/mm3
Hemoglobin ≤9 g/dL
White blood count ≤3000 cells/mm3.
Single group
Fruquintinib Combined With Chemotherapy
DrugThe 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.
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.
Incidence of toxicity of 5FU in combination with fruquintinib in first-line metastatic colorectal cancer patients
To assess the safety profile, toxicity (all grades of adverse event rates) of 5-Fluorouracil (5FU)-based therapy in combination with fruquintinib in patients with locally advanced unresectable or metastatic colorectal cancer (mCRC) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.
Duration of the response of 5FU in combination with fruquintinib in first-line metastatic colorectal cancer patients
To evaluate the duration of the response of 5-Fluorouracil (5FU)-based therapy in combination with fruquintinib in the first-line setting for locally advanced unresectable or metastatic colorectal cancer (mCRC) patients from onset of response to progression or death, whichever occurs earlier according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria and investigator's tumor assessment.
Overall Survival rate of first-line metastatic colorectal cancer patients with 5FU in combination with fruquintinib
To evaluate the overall survival (OS) rate of patients with locally advanced unresectable or metastatic colorectal cancer (mCRC) treated with 5-Fluorouracil (5FU)-based therapy in combination with fruquintinib at 6 and 12 months.
Overall Response Rate of first-line metastatic colorectal cancer patients with 5FU in combination with fruquintinib
To evaluate the overall response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) of patients with locally advanced unresectable or metastatic colorectal cancer (mCRC) treated with 5-Fluorouracil (5FU)-based therapy in combination with fruquintinib at 6 and 12 months.
Changes in health-related quality of life for first-line metastatic colorectal cancer patients with 5FU in combination with fruquintinib
Changes in health-related quality of life from baseline to months 6 and 12, as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). The EORTC QLQ-C30 scores range from 0 to 100. For global health status/quality of life and functional scales (e.g., physical, role, emotional, cognitive, social), higher scores indicate better outcomes (improved quality of life or functioning). For symptom scales/items (e.g., fatigue, pain, nausea/vomiting), higher scores indicate worse outcomes (more severe symptoms).
Time to treatment failure of 5FU in combination with fruquintinib in first-line patients with metastatic colorectal cancer
The number of months from beginning of treatment to the time of progression of patients on 5-Fluorouracil (5FU)-based therapy in combination with fruquintinib for patients with locally advanced unresectable or metastatic colorectal cancer (mCRC).
Click on the lead sponsor to view all of their trials.
The Methodist Hospital Research Institute
Lead sponsor
Takeda Development Center Americas, Inc.
Collaborator
