A Phase II Study of Fruquintinib Combined With Anti-EGFR Monoclonal Antibody in Third-Line Treatment of RAS Wild-Type Metastatic Colorectal Cancer
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.
• At least one measurable lesion according to RECIST 1.1 criteria.
• ECOG performance status of 0-1.
• Estimated life expectancy ≥ 12 weeks.
• Prior treatment with oxaliplatin- and irinotecan-based therapy, or failure of at least two prior standard regimens.
• Prior treatments must have included fluoropyrimidine, oxaliplatin, and irinotecan (with or without bevacizumab or cetuximab).
⁃ Treatment failure defined as disease progression during therapy or within 3 months after last treatment, or intolerance to toxicity.
⁃ Recurrence within 6 months after adjuvant/neoadjuvant therapy is considered as first-line failure.
⁃ Adequate organ function within 7 days prior to enrollment:
∙ ANC ≥ 1.5 × 10⁹/L
‣ Platelets ≥ 80 × 10⁹/L
‣ Hemoglobin ≥ 8 g/dL
‣ Total bilirubin ≤ 1.5 × ULN
‣ AST/ALT ≤ 2.5 × ULN (≤ 5 × ULN in liver metastasis)
‣ Serum creatinine ≤ 1.5 × ULN and creatinine clearance ≥ 50 mL/min
‣ INR ≤ 1.5 or APTT ≤ 1.5 × ULN
⁃ No receipt of blood products or growth factors within 14 days prior to enrollment.
⁃ Able and willing to comply with study procedures and follow-up.