NCT07051785

Fruquintinib vs Bevacizumab Combined With Irinotecan Liposome and Capecitabine as Second-Line Therapy for Advanced Metastatic Colorectal Cancer

Fruquintinib vs Bevacizumab Combined With Irinotecan Liposome and Capecitabine as Second-Line Therapy for Advanced Metastatic Colorectal Cancer：A Multicenter Randomized Controlled Trial

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 68 (estimated)
• Sponsor: Liu Huang · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This study is divided into two phases. The first phase aims to preliminarily evaluate the efficacy and safety of fruquintinib in combination with irinotecan liposome and capecitabine as second-line therapy for advanced metastatic colorectal cancer. The second phase is designed to further assess the efficacy and safety of fruquintinib in combination with irinotecan liposome and capecitabine compared to bevacizumab in combination with chemotherapy, also as second-line treatment for advanced metastatic colorectal cancer. The first phase is a single-arm study, while the second phase is a randomized (1:1) controlled trial. Entry into the second phase is determined by the investigators based on the efficacy results from the first phase study: if the primary endpoint of progression-free survival (PFS) is met in the first phase, participants will proceed to the second phase study. In the second phase, randomization is stratified according to the RAS status and the presence of disease progression within six months of adjuvant or neoadjuvant therapy. In the second phase, patients will be ramdomly assigned to receive fruquintinib(4mg/d, PO, D1-14, Q3W) in combination with irinotecan liposome(56mg/m2, ivgtt, D1, Q3W) and capecitabine(800mg/m2, PO, BID, D1-14, Q3W) or bevacizumab(7.5mg/kg, ivgtt, D1, Q3W) in combination with the same chemotherapy. Every three weeks is a cycle.

Detailed description

Colorectal cancer (CRC) is one of the most common malignant tumors in the gastrointestinal tract, ranking third globally in terms of incidence and second in terms of mortality. The incidence rate is higher in developed countries compared to developing countries. According to statistical data from the Chinese Cancer Center in 2018, CRC ranks third and fifth in terms of incidence and mortality, respectively. Due to its insidious onset and non-specific clinical manifestations, the early detection rate of CRC is relatively low. Approximately 50% to 60% of patients diagnosed at an advanced stage, often with metastasis. The treatment of colorectal cancer (CRC) encompasses surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. For patients with early-stage CRC, curative surgery is the primary therapeutic approach; however, recurrence and metastasis remain potential risks. In contrast, for patients with metastatic, unresectable CRC (mCRC), the treatment aims to prolong survival and improve quality of life . According to the guidelines, systemic therapy primarily involves chemotherapy and, in some cases, the combination of chemotherapy and targeted agents . Traditional chemotherapeutic agents include 5-FU, capecitabine, irinotecan, oxaliplatin, and etc.. Commonly used targeted therapies include monoclonal antibodies, such as bevacizumab and cetuximab. The use of these biologics which are blocking key pathways in the progression of mCRC has further prolonged patient survival. However, most patients with unresectable metastatic CRC experience disease progression or develop unacceptable toxicity during first-line systemic therapy, necessitating the initiation of second-line treatment. The goal of this clinical trial is to evaluate the efficacy and safety of fruquintinib combined with irinotecan liposome and capecitabine as second-line therapy for advanced metastatic colorectal cancer in patients histopathologically confirmed unresectable colorectal cancer, who have previously failed or were intolerant to standard treatment. This study is a multicenter, two-stage, randomized controlled trial. Participants were enrolled from patients who had previously received standard first-line therapy based on oxaliplatin, which failed or was not tolerated. The study aims to further evaluate the efficacy and safety of the combination of fruquintinib, irinotecan liposome, and capecitabine compared to bevacizumab combined with chemotherapy as second-line treatment for metastatic, unresectable colorectal cancer (mCRC). Study Design: Stage 1: Single-Arm Cohort * A total of 28 patients were enrolled in this phase. * Participants received fruquintinib, irinotecan liposome, and capecitabine for 6-8 cycles. * If no disease progression was observed after the initial treatment, patients were transitioned to maintenance therapy with fruquintinib and capecitabine. * Imaging assessments were conducted every 6 weeks (±7 days), and responses were evaluated according to RECIST 1.1 criteria. Stage 2: Randomized (1:1) Controlled Trial * Based on the results of the first stage, investigators determined whether to proceed to the second stage. If the primary endpoint of progression-free survival (PFS) was met in the first stage, participants were eligible for the second stage. * A total of 40 patients were planned to be enrolled in this phase. * Randomization was stratified based on RAS mutation status and disease progression within 6 months of adjuvant or neoadjuvant therapy. * Participants were randomly assigned to two groups (A and B), each consisting of 20 patients: * Group A: Fruquintinib + irinotecan liposome + capecitabine * Group B: Bevacizumab + irinotecan liposome + capecitabine * After 6-8 cycles of treatment, patients who had no disease progression were transitioned to maintenance therapy: * Group A: Fruquintinib + capecitabine * Group B: Bevacizumab + capecitabine * Imaging assessments were conducted every 6 weeks (±7 days), and responses were evaluated according to RECIST 1.1 criteria

Conditions

• Colorectal Cancer (CRC)

Interventions

Type	Name	Description
DRUG	Fruquintinib+Irinotecan Liposome+Capecitabine	Stage 1: Participants received fruquintinib, irinotecan liposome, and capecitabine for 6-8 cycles. If no disease progression was observed after the initial treatment, patients were transitioned to maintenance therapy with fruquintinib and capecitabine. Stage 2: if the primary endpoint of progression-free survival (PFS) was met in the first stage, participants were eligible for the second stage. Participants were randomly assigned to two groups (A and B), Group A: Fruquintinib + irinotecan liposome + capecitabine. After 6-8 cycles of treatment, patients who had no disease progression were transitioned to maintenance therapy with Fruquintinib + capecitabine
DRUG	Bevacizumab+Irinotecan Liposome+Capecitabine	Stage 2: if the primary endpoint of progression-free survival (PFS) was met in the first stage, participants were eligible for the second stage. Participants were randomly assigned to two groups (A and B), Group B: Bevacizumab + irinotecan liposome + capecitabine. After 6-8 cycles of treatment, patients who had no disease progression were transitioned to maintenance therapy with bevacizumab + capecitabine

Timeline

• Start date: 2025-07-07
• Primary completion: 2027-07-06
• Completion: 2028-07-06
• First posted: 2025-07-04
• Last updated: 2025-07-04