A Phase II Study Investigating Fruquintinib Plus FOLFIRI as Second-Line Treatment for Participants With Metastatic Colorectal Cancer (mCRC)

Phase 2

Not yet recruiting

• Conditions: Colon Cancer; Rectal Cancer; Colorectal Cancer; Colorectal Cancer (CRC)
• Interventions: Drug: fruquintinib; Drug: FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)

• Registration Number: NCT07011576
• Lead Sponsor: SCRI Development Innovations, LLC

Brief Summary

This is an open-label multicenter, single-arm Phase II study of Fruquintinib in combination with FOLFIRI (leucovorin calcium (folinic acid), fluorouracil, and irinotecan) in participants with metastatic colorectal cancer (mCRC). The main goals of this study are to:

* Evaluate the efficacy of the combination of fruquintinib + FOLFIRI in the 2nd-line mCRC setting

* Evaluate the safety of the combination of fruquintinib + FOLFIRI

Detailed Description

Fruquintinib is an FDA approved cancer medication that works by targeting proteins called vascular endothelial growth factor receptors (VEGFRs). VEGFRs are important in the creation of new blood vessels. As a highly-selective and potent VEGFR inhibitor, fruquintinib helps block new blood vessels that would provide nutrients and oxygen to cancerous tumors from forming. It is a small molecule anti-tumor drug with a novel chemical structure that belongs to the quinazoline class.

This study is an open-label Phase II study designed to evaluate the efficacy and safety of fruquintinib + FOLFIRI in 2nd-line setting mCRC participants who have been previously treated with FOLFOX (folinic acid, fluorouracil, and oxaliplatin) and Bevacizumab-based first-line therapy. Up to 60 participants will receive concurrent fruquintinib and FOLFIRI according to standard guidelines of treatment of mCRC.

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-05
• Study First Submitted QC: 2025-06-05
• Last Update Submitted: 2025-06-05
• Study First Posted: 2025-06-09
• Last Update Posted: 2025-06-09
• Study Start: 2025-07
• Primary Completion: 2027-01
• Study Completion: 2027-06

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Confirmed mCRC ; histologically documented adenocarcinoma of the colon or rectum with at least one measurable lesion according to RECIST v1.
• Genetic aberrations are allowed, except for microsatellite instability high (MSI-H) and BRAF V600
• Participants must have received FOLFOX (folinic acid, fluorouracil, and oxaliplatin) and Bevacizumab- based first-line therapy for mCRC
• At least 18 years-of-age at the time of signature of the Informed Consent Form (ICF)
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 2

Key

Exclusion Criteria

• Current treatment with other anticancer treatments within 21 days of the first dose of study treatment
• Major surgery within 4 weeks of the first planned dose of study treatment
• More than one treatment received for mCRC prior to signing the ICFs
• Uncontrolled, symptomatic brain metastases
• Uncontrolled, symptomatic gastrointestinal disease
• Patients with uncontrolled hypertension
• Women who are pregnant, nursing, or plan to become pregnant while in the study and for at least 6 months after the last administration of study chemotherapy
• Men who plan to father a child while in the study and for at least 6 months after the last administration of study chemotherapy
• Documented major electrocardiogram (ECG) abnormalities which are clinically significant.
• Symptomatic or uncontrolled brain metastases, spinal cord compression, or leptomeningeal disease requiring concurrent treatment
• Presence of other active invasive cancers other than the one treated in this study within 5 years prior to screening

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fruquinitinib + FOLFIRI	fruquintinib	Participants will receive an assigned dose level of fruquintinib in combination with FOLFIRI. Cycles will be 28 days, where participants will take fruquinitinib orally on Days 1 through 21 in combination with FOLFIRI intravenous infusion (IV) every 2 weeks. Up to 60 participants will be enrolled.
Fruquinitinib + FOLFIRI	FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)	Participants will receive an assigned dose level of fruquintinib in combination with FOLFIRI. Cycles will be 28 days, where participants will take fruquinitinib orally on Days 1 through 21 in combination with FOLFIRI intravenous infusion (IV) every 2 weeks. Up to 60 participants will be enrolled.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS) rate at 6 months	Every 2 cycles from cycle 1 day 1, until disease progression or death, up to 2 years. Each cycle is 28 days.	Progression-Free Survival (PFS) rate at 6 months, defined as the percentage of participants at 6 months who have not experienced disease progression as defined by the RECIST Version 1.1 criteria or death on study. Participants who are alive and free from disease progression will be censored at the date of last tumor assessment.

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	Every 2 cycles from cycle 1 day 1, until disease progression or death, up to 2 years. Each cycle is 28 days.	Objective Response Rate (ORR), defined as the proportion of participants with confirmed CR or PR (i.e., 2 CRs or PRs at least 4 weeks apart) according to the RECIST Version 1.1.
Duration of response (DoR)	Every 2 cycles from cycle 1 day 1, until disease progression or death, up to 2 years. Each cycle is 28 days.	Duration of Response (DoR), defined as the duration from the first documented response to the date of first documented PD or death due to any cause. In case a participant does not experience PD or death, DoR is censored at the date of last adequate tumor assessment (defined as an assessment of CR, PR, or SD). DoR analysis will include only responders (PR or better).
Disease control response rate (DCR)	Every 2 cycles from cycle 1 day 1, until disease progression or death, up to 2 years. Each cycle is 28 days.	Disease Control Response Rate (DCR), defined as the proportion of participants with a best overall response of CR, PR, or SD.
Number of participants with treatment emergent adverse events	Every 28 day cycle, from signed informed consent to 30 days after treatment discontinuation up to 1 year.	Using CTCAE V5.0
Overall Survival (OS)	From cycle 1 day 1 up to 2 years	Overall Survival (OS), defined as the time from the first day of study drug administration (Day 1) to death. Participants who are alive will be censored at the date of last known date alive.