NCT07362836

Fruquintinib Versus Bevacizumab Plus Chemotherapy in Second-Line RAS-Mutant Metastatic Colorectal Cancer (FRU-RAS)

Fruquintinib Versus Bevacizumab Plus Chemotherapy as Second-Line Therapy for Patients With RAS-Mutant Metastatic Colorectal Cancer (FRU-RAS): A Multicenter Randomized Controlled Trial

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 224 (estimated)
• Sponsor: Fudan University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to evaluate the efficacy and safety of fru+chemo as second-line therapy for patients with RAS-Mutant Metastatic Colorectal Cancer, especially when compared with the standard therapy BEV+chemo. The trial aims to provide this kind of patients with a more beneficial therapeutic option. Eligible patients were randomly assigned to the experimental group or the control group at a ratio of 1:1, Experimental group: Patients received fruquintinib combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen), Control group: Patients received bevacizumab combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen),

Detailed description

Eligible patients were randomly assigned to the experimental group or the control group at a ratio of 1:1, stratified by bevacizumab treatment history (yes vs no), and metastatic sites (≤2 vs \>2). Experimental group: Patients received fruquintinib combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen), with the choice of oxaliplatin-based or irinotecan-based chemotherapy regimen depending on the previous chemotherapy regimen (chemotherapy switch): fruquintinib: 4mg, qd po, d1-21, q4w; FOLFIRI regimen: irinotecan 180mg/m2 intravenous infusion for 30-90min on days 1 and 15; LV 400mg/m2 intravenous infusion for 2h on days 1 and 15; 5-FU 400mg/m2 intravenous push on days 1 and 15, followed by 1200mg/(m2∙d) × 2d continuous intravenous infusion (total 2400mg/m2, infusion 46-48h); every 4 weeks as a treatment cycle. mFOLFOX6 regimen: oxaliplatin 85mg/m2 intravenous infusion for 2h on days 1 and 15; LV 400mg/m2 intravenous infusion for 2h on days 1 and 15; 5-FU 400mg/m2 intravenous push on days 1 and 15, followed by 1200mg/(m2∙d) × 2d continuous intravenous infusion (total 2400mg/m2, infusion 46-48h); every 4 weeks as a treatment cycle. Control group: Patients received bevacizumab combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen), with the choice of oxaliplatin-based or irinotecan-based chemotherapy regimen depending on the previous chemotherapy regimen (chemotherapy switch): bevacizumab: 5mg/kg, ivgtt, d1, 15, q4w; FOLFIRI regimen: irinotecan 180mg/m2 intravenous infusion for 30-90min on days 1 and 15; LV 400mg/m2 intravenous infusion for 2h on days 1 and 15; 5-FU 400mg/m2 intravenous push on days 1 and 15, followed by 1200mg/(m2∙d) × 2d continuous intravenous infusion (total 2400mg/m2, infusion 46-48h); every 4 weeks as a treatment cycle. mFOLFOX6 regimen: oxaliplatin 85mg/m2 intravenous infusion for 2h on days 1 and 15; LV 400mg/m2 intravenous infusion for 2h on days 1 and 15; 5-FU 400mg/m2 intravenous push on days 1 and 15, followed by 1200mg/(m2∙d) × 2d continuous intravenous infusion (total 2400mg/m2, infusion 46-48h); every 4 weeks as a treatment cycle. During the combination treatment period, the tumor response was evaluated by imaging every 8 weeks. After at least 6 cycles of continuous administration, the following evaluations were made: ① If the patient met the conditions for conversion therapy, radical local treatments such as surgical resection or radiofrequency ablation could be performed. Patients in the fruquintinib group needed to discontinue the drug for about 2 weeks before surgery, while those in the bevacizumab group needed to discontinue for about 6 weeks. ② Patients who achieved disease control entered the maintenance treatment stage and received fruquintinib combined with chemotherapy or bevacizumab combined with chemotherapy, with the chemotherapy regimen determined by the doctor. The treatment continued until disease progression, intolerable toxicity, or withdrawal of informed consent occurred. During the maintenance treatment period, the tumor response was evaluated by imaging every 8 weeks. Safety observation indicators included adverse events, changes in laboratory indicators, vital signs, and electrocardiogram changes. The subsequent tumor treatment and survival follow-up after progression were recorded.

Conditions

• Colorectal Cancer

Interventions

Type	Name	Description
DRUG	fruquintinib+chemotherapy	fruquintinib combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen)
DRUG	bevacizumab+chemotherapy	bevacizumab combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen)

Timeline

• Start date: 2026-01-31
• Primary completion: 2028-12-30
• Completion: 2030-01-30
• First posted: 2026-01-23
• Last updated: 2026-01-23