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

NCT07362836 | Not Yet Recruiting Phase 3

• 1 other identifier: HMPL-013-FLAG-C140
• Study Type: interventional
• Target: 224
• Locations: 0 countries
• Sites: N/A

Brief 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),

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival

  Progression-Free Survival (PFS) is a time-to-event outcome commonly used as a primary or secondary endpoint in oncology clinical trials. It quantifies the duration a patient lives without disease progression or death, providing an early indicator of treatment efficacy.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months

Secondary Outcomes (3)

• Objective Response Rate

  ORR will be assessed up to Week 24 after randomization

• Disease Control Rate

  DCR will be assessed up to Week 24 after randomization.

• Overall Survival

  From date of randomization until the date of death from any cause, assessed up to 60 months

Study Arms (2)

fruquintinib+chemotherapy

EXPERIMENTAL

fruquintinib combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen)

Drug: fruquintinib+chemotherapy

bevacizumab+chemotherapy

ACTIVE COMPARATOR

bevacizumab combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen)

Drug: bevacizumab+chemotherapy

Interventions

fruquintinib+chemotherapy DRUG

fruquintinib combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen)

fruquintinib+chemotherapy

bevacizumab+chemotherapy DRUG

bevacizumab combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen)

bevacizumab+chemotherapy

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 participate in the study, sign the informed consent form, and have good compliance.
• years ≤ age ≤ 75 years.
• Histologically and/or cytologically confirmed unresectable metastatic colorectal cancer.
• RAS mutant type.
• Previously received chemotherapy based on fluoropyrimidines (5-fluorouracil or capecitabine, etc.), oxaliplatin or irinotecan; previous adjuvant/neoadjuvant therapy is allowed. If recurrence or metastasis occurs during or within 6 months after adjuvant/neoadjuvant therapy, it is considered as the failure of first-line systemic chemotherapy for advanced disease.
• Patients must have at least one measurable lesion (RECIST 1.1).
• ECOG performance status 0-1.
• Expected survival ≥ 12 weeks.
• Blood tests (without blood transfusion within 14 days) 1) Absolute neutrophil count ≥ 1.5×10\^9/L, platelet count ≥ 100×10\^9/L, hemoglobin concentration ≥ 9g/dL; 2) Liver function tests (AST and ALT ≤ 2.5×ULN, bilirubin ≤ 1.5×ULN; if there is liver metastasis, AST and ALT ≤ 5×ULN); 3) Renal function (serum creatinine (Cr) ≤ 1.5×ULN, or creatinine clearance rate (CCr) ≥ 60ml/min); 4) Coagulation, international normalized ratio (INR) ≤ 1.5×ULN, prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5×ULN; 5) Thyroid function, thyroid stimulating hormone (TSH) ≤ upper limit of normal (ULN); if abnormal, FT3 and FT4 levels should be examined, and patients with normal FT3 and FT4 levels can be included.
• Women of childbearing age are willing to use medically approved effective contraceptive measures (such as intrauterine devices, contraceptives or condoms) during the study and for 3 months after the last administration of the study drug; for male subjects whose partners are of childbearing age, it is recommended to take effective contraceptive measures during the study and for 3 months after the last administration of the study drug.

You may not qualify if:

• Enrolled in another clinical study within the 4 weeks prior to enrollment in this study;
• Previously received anti-angiogenic small molecule targeted drug treatment, such as fruquintinib, etc.;
• Symptomatic brain or leptomeningeal metastases (except for those who have undergone local radiotherapy or surgery for brain metastases for more than 6 months and have stable disease control);
• Experienced severe infection within 4 weeks prior to enrollment (e.g., requiring intravenous infusion of antibiotics, antifungal drugs, or antiviral drugs);
• Hypertension that cannot be well controlled with antihypertensive drugs (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg);
• Had active bleeding or coagulation disorders within 2 months prior to enrollment, had a bleeding tendency or was receiving thrombolytic therapy, and was assessed by the investigator as unsuitable for enrollment;
• Had active heart disease within 6 months prior to treatment, including myocardial infarction, severe/unstable angina pectoris. Echocardiography showed left ventricular ejection fraction \< 50%, or had poorly controlled arrhythmia;
• Had other malignant tumors within 5 years prior to enrollment or at the same time (except for cured basal cell carcinoma of the skin and cervical carcinoma in situ);
• Known to be allergic to the study drug or any of its excipients;
• Unable to take oral medication or the investigator judged that the subject had a condition that affected drug absorption;
• Pregnant (positive pregnancy test before medication) or breastfeeding women;
• Had active or uncontrolled severe infections 1) Known human immunodeficiency virus (HIV) infection; 2) Known history of clinically significant liver disease, including viral hepatitis \[known hepatitis B virus (HBV) carriers must be excluded from active HBV infection, i.e., HBV DNA positive (\>1×10\^4 copies/mL or \>2000 IU/mL); 3) Known hepatitis C virus (HCV) infection and HCV RNA positive (\>1×10\^3 copies/mL), or other hepatitis, liver cirrhosis;
• Urinalysis indicated proteinuria ≥ 2+, and 24-hour urine protein quantification \> 1.0g;

Sponsors & Collaborators

• Fudan University: 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 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: January 4, 2026
• First Posted: January 23, 2026
• Study Start: January 31, 2026
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): January 30, 2030
• Last Updated: January 23, 2026

Record last verified: 2026-01