This study aims to evaluate the effectiveness and safety of combining fruquintinib (an oral anti-angiogenesis drug) with cetuximab-beta (an anti-EGFR antibody) in patients with RAS wild-type metastatic colorectal cancer who have already failed at least two lines of standard treatments.
Standard therapies for metastatic colorectal cancer often include fluorouracil, oxaliplatin, and irinotecan. However, many patients eventually experience disease progression, and treatment options become limited. Fruquintinib and cetuximab-beta work through different mechanisms: fruquintinib blocks tumor blood vessel growth, while cetuximab-beta blocks EGFR-related cancer cell growth signals. Using these two drugs together may provide additional benefit for patients whose cancer no longer responds to other treatments.
This study will enroll 46 patients who meet the eligibility criteria. All participants will take fruquintinib by mouth once daily (3 weeks on and 1 week off) and receive cetuximab-beta by intravenous infusion every 2 weeks. Treatment will continue until the cancer progresses or side effects become intolerable.
Doctors will monitor tumor changes every 8 weeks using CT or MRI scans and will also collect blood samples over time to measure circulating tumor DNA (ctDNA), which may help track how the cancer responds to treatment. Safety will be assessed through physical exams, lab tests, and monitoring of side effects.
The main goal of the study is to determine the objective response rate (ORR)-how many patients experience measurable tumor shrinkage. Secondary goals include progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety outcomes.
Age 18-75 years, inclusive.
Fully informed about the study and willing to sign written informed consent.
Histologically confirmed metastatic or advanced colorectal adenocarcinoma.
Tumor confirmed as NRAS, KRAS, and BRAF wild-type.
Unable or unwilling to comply with the study protocol.
Prior treatment with VEGFR tyrosine kinase inhibitors (e.g., regorafenib).
Participation in another clinical trial within 4 weeks.
Systemic anticancer therapy within 4 weeks before enrollment.
Single group
Fruquintinib plus Cetuximab-beta
DrugPatients receive fruquintinib 5 mg orally once daily for 3 consecutive weeks followed by 1 week off in a 4-week cycle. Cetuximab-beta is administered intravenously at 500 mg/m² every 2 weeks. Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision. Tumor assessments are performed every 8 weeks using RECIST 1.1 criteria. Safety is monitored through physical examinations, laboratory tests, vital signs, ECG, echocardiography, and adverse event reporting. Circulating tumor DNA (ctDNA) is collected at baseline, every 8 weeks during treatment, at progression, and 4-6 weeks after progression to evaluate molecular response and resistance dynamics. The regimen is designed for patients with metastatic colorectal cancer who previously failed standard fluoropyrimidine, oxaliplatin, and irinotecan-based therapies and who have RAS wild-type tumors.
Objective Response Rate (ORR)
The proportion of patients with a confirmed complete response or partial response using RECIST 1.1
Progression-Free Survival (PFS)
The time from the date of the first administration of this regimen to the date of first documented disease progression or death due to any cause.
Disease Control Rate (DCR)
Proportion of patients achieving complete response (CR), partial response (PR), or stable disease (SD) according to RECIST 1.1.
Overall Survival (OS)
Time from first dose of study treatment until death from any cause.
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events
Number and proportion of participants experiencing treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. Safety assessments include laboratory tests, vital signs, 12-lead electrocardiography, echocardiography, and clinically significant physical examination findings.
Circulating Tumor DNA (ctDNA)
Quantitative and qualitative changes in ctDNA levels at baseline, during treatment, at progression, and 4-6 weeks post-progression to evaluate molecular response and resistance patterns.
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