fruquintinib plus folfiri in ras-mutated metastatic colorectal cancer

Conditions: Colorectal Cancer

Summary: ras mutations are found in nearly half of colorectal cancer patients. however, except for g12c mutation, no driven gene targeted drug can be used. the commonly first-line used treatment regimen is bevacizumab combined with chemotherapy. angiogenesis is an important therapeutic target in colorectal carcinoma. fruquintinib is an oral small molecule inhibitor of vegfr1/2/3, has approved for the third-line treatment of refractory colorectal cancer.

this is a prospective ,single-center, open labeled, single-arm phase ii study exploring the efficacy and safety of fruquintinib combined with folfiri as second-line treatment of ras-mutated metastatic colorectal cancer (mcrc) in patients with disease progression during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.

Eligibility criteria:
inclusion criteria: 1. histological or cytological confirmed colorectal cancer; 2. ras mutation; 3. expected survival \>12 weeks; 4. patients had disease progression during or within 3 months of the last dose of first-line therapy, which must include bevacizumab combined with oxaliplatin, and a fluoropyrimidine; 5. ecog ps 0-1; 6. at least one measurable lesion (according to recist1.1); 7. adequate hepatic, renal, heart, and hematologic functions; 8. negative serum pregnancy test at screening for women of childbearing potential. - exclusion criteria: 1. msi-h / dmmr; 2. received radiation therapy, surgical procedure, immunotherapy or other investigational drugs within 4 weeks prior to treatment ; 3. prior treatment with anti-angiogenic small molecule targeted drugs, such as fruquintinib, etc; 4. prior treatment with an irinotecan-based chemotherapy regimen; 5. symptomatic brain or meningeal metastases (except for patients with bms who have received local radiotherapy or surgery for more than 6 months and whose disease is stable); 6. severe infection (e.g., requiring intravenous antibiotics, antifungal drugs, or antiviral drugs) within 4 weeks prior to treatment; 7. patients with hypertension that cannot be well controlled by antihypertensive medication (systolic blood pressure ≥140 mmhg or diastolic blood pressure ≥90 mmhg); 8. patients who had active bleeding or coagulopathy within 2 months before enrollment, had a tendency to bleed, or were receiving thrombolytic therapy and were considered by the investigator to be ineligible for enrollment; 9. active heart disease, including myocardial infarction, severe/unstable angina, 6 months prior to treatment. echocardiography examination left ventricular ejection fraction \< 50%, arrhythmia control is not good; 10. the patient has had other malignant tumors within 5 years (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix); allergy to the study drug or any of its excipients; 11. the patient is unable to take the drug orally, or the patient has a condition judged by the investigator to affect the absorption of the drug; women who are pregnant (with a positive pregnancy test before medication) or breastfeeding; 12. urine routine showed urine protein ≥2+, and 24-hour urine protein level \>1.0g; other conditions deemed by the investigator to be ineligible for inclusion in the study.

Keywords: fruquintinib ras-mutant second-line