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

NCT07051785 | Not Yet Recruiting Phase 2

• 1 other identifier: HMPL-013-FLAG-C135
• Study Type: interventional
• Target: 68
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Colorectal Cancer (CRC)

Keywords

Colorectal Cancer; Fruquintinib; Second-Line

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  time from randomization to the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator

  one year

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  one year

• Disease Control Rate (DCR)

  one year

• Overall survival (OS)

  two years

Study Arms (2)

Fruquintinib+Irinotecan Liposome+Capecitabine

EXPERIMENTAL

fruquintinib(4mg/d, PO, D1-14, Q3W) + irinotecan liposome(56mg/m2, ivgtt, D1, Q3W) + capecitabine(800mg/m2, PO, BID, D1-14, Q3W), every three weeks is a cycle.

Drug: Fruquintinib+Irinotecan Liposome+Capecitabine

Bevacizumab+Irinotecan Liposome+Capecitabine

ACTIVE COMPARATOR

bevacizumab(7.5mg/kg, ivgtt, D1, Q3W)+irinotecan liposome(56mg/m2, ivgtt, D1, Q3W) + capecitabine(800mg/m2, PO, BID, D1-14, Q3W), every three weeks is a cycle.

Drug: Bevacizumab+Irinotecan Liposome+Capecitabine

Interventions

Fruquintinib+Irinotecan Liposome+Capecitabine DRUG

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

Fruquintinib+Irinotecan Liposome+Capecitabine

Bevacizumab+Irinotecan Liposome+Capecitabine DRUG

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

Bevacizumab+Irinotecan Liposome+Capecitabine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients voluntarily enrolled in the study and signed an informed consent form, were compliant and cooperated with follow-up visits;
• Patients with metastatic colorectal adenocarcinoma confirmed by pathology or histology;
• Age: 18-75 (inclusive of 18 and 75), male or female;
• Patients who have previously failed or were intolerant to first-line standard therapy (recurrence within 6 months of the end of adjuvant chemotherapy is considered first-line treatment failure).
• ECOG score: 0-1;
• At least one measurable lesion (based on RECIST 1.1 criteria);
• Major organs and bone marrow function were essentially normal (no blood components or cell growth factors had been used in the 14 days prior to enrollment):
• Neutrophil count ≥ 1.5 × 10⁹/L;
• Platelet count ≥ 100 × 10⁹/L;
• Hemoglobin ≥ 90 g/L;
• Coagulation parameters: International Normalized Ratio (INR) ≤ 1.5 × ULN; Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN;
• Liver function: Total bilirubin ≤ 1.5 × ULN; Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 2.5 × ULN (with an exception for patients with liver metastases, where ALT/AST may be up to 5 × ULN);
• Renal function: Serum creatinine ≤ 1.5 × ULN; Creatinine clearance (CCr) ≥ 50 mL/min.
• Female participants of reproductive age must undergo a serum or urinalysis that shows no pregnancy within 14 days before the first dose of study treatment. Male or female patients of childbearing potential will voluntarily use an effective method of contraception, e.g., double-barrier contraception, condoms, oral or injectable contraceptives, intrauterine devices, etc., during the study period and for at least 6 months after the last dose of study medication.

You may not qualify if:

• History of major surgery or severe trauma within 4 weeks prior to the initiation of the study drug.
• Use of immunosuppressive agents, including systemic or locally absorbed corticosteroids, for immunosuppressive purposes, with a daily dose of prednisone \>10 mg or equivalent, and continued us within 2 weeks prior to enrollment.
• Prior exposure to any irinotecan-containing chemotherapy regimen.
• Reception of live attenuated vaccines within 4 weeks prior to the initiation of the study drug.
• Prior treatment with anti-angiogenic small-molecule targeted therapy.
• Presence of any active autoimmune disease or a history of autoimmune disorders (e.g., autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypopituitarism, vasculitis, nephritis and etc.; not include vitiligo or childhood asthma that has fully resolved and does not require intervention in adulthood; asthma requiring bronchodilator therapy for medical management is included).
• History of other malignancies within the past 5 years, except for curatively resected skin basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma in situ.
• Congenital or acquired immunodeficiency (e.g., HIV) or active hepatitis (e.g., hepatitis B: HBsAg positive and HBV DNA ≥ 10⁴ copies/mL or \>2000 IU/mL; hepatitis C: HCV antibody positive).
• Uncontrolled cardiac clinical symptoms or diseases, including: (1) NYHA classification \>2 heart failure; (2) Unstable angina pectoris; (3) Myocardial infarction within 1 year; (4) Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention.
• Hypertension that is not well-controlled with antihypertensive medication (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg).
• Active or uncontrolled severe infections (≥ CTCAE grade 2 infection).
• Urine routine suggests urinary protein ≥2+ and the amount of urinary protein \>1.0g in 24 hours.
• Patients with evidence or history of significant bleeding tendency within 3 months prior to enrollment (bleeding \>30 mL within 3 months, vomiting blood, black stool, blood in stool), hemoptysis (\>5 mL of fresh blood within 4 weeks), or a thromboembolic event (including stroke events and/or transient ischemic attack) within 12 months;
• Active peptic ulcer disease, ulcerative colitis, or uncontrolled gastrointestinal bleeding, or any gastrointestinal condition judged by the investigator, which may cause gastrointestinal bleeding, perforation, or bowel obstruction.
• Female participants who are pregnant (positive pregnancy test prior to drug administration) or are breastfeeding;.

Sponsors & Collaborators

• Liu Huang: lead

MeSH Terms

Conditions

Colorectal Neoplasms

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 26, 2025
• First Posted: July 4, 2025
• Study Start: July 7, 2025
• Primary Completion (Estimated): July 6, 2027
• Study Completion (Estimated): July 6, 2028
• Last Updated: July 4, 2025

Record last verified: 2025-06