The Efficacy and Safety of Fruquintinib Plus FOLFIRI/FOLFOX as Second-line Treatment in Patients With RAS-mutant Metastatic Colorectal Cancer

Fudan University

Status and phase: Not yet enrolling; Phase 2

Conditions: Metastatic Colorectal Cancer

Treatments: Drug: Fruquintinib; Drug: mFOLFOX6; Drug: FOLFIRI

Study type: Interventional

Funder types: Other

Identifiers

NCT05634590

HMPL-013-FLAG-C119

Details and patient eligibility

About

RAS mutations are found in nearly half of colorectal cancer patients. However, there is no targeted driver gene drugs have been approved for RAS-mutated patients. For RAS mutant metastatic colorectal cancer, the commonly used treatment regimen is bevacizumab combined with chemotherapy.

Full description

This is a single-center, open, single-arm study exploring the efficacy and safety of fruquintinib combined with FOLFIRI/FOLFOX in the treatment of RAS-mutated metastatic colorectal cancer (mCRC) who failed standard therapy. Patients will receive fruquinitinib combined with chemotherapy (FOLFOX or FOLFIRI regimens), which depend on the previous chemotherapy regimen (chemotherapy switch).

Enrollment: 68 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• ≥18 years
• Histological or cytological confirmed colorectal cancer;
• RAS mutation
• Expected survival >12 weeks;
• Fail in previous standard therapy, which must include FOLFOX/FOLFIRI;
• ECOG PS 0-1;
• At least one measurable lesion (according to RECIST1.1);
• Adequate hepatic, renal, heart, and hematologic functions;
• Negative serum pregnancy test at screening for women of childbearing potential.

Exclusion criteria

• Received other investigational drugs within 4 weeks prior to treatment;
• Prior treatment with anti-angiogenic small molecule targeted drugs, such as fruquintinib, etc;
• 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);
• Severe infection (e.g., requiring intravenous antibiotics, antifungal drugs, or antiviral drugs) within 4 weeks prior to treatment;
• Patients with hypertension that cannot be well controlled by antihypertensive medication (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);
• 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;
• 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;
• 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;
• 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;
• 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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68 participants in 1 patient group

Fruquintinib plus FOLFIRI/FOLFOX

Experimental group

Description:

Patients will receive fruquintinib plus FOLFIRI/FOLFOX. Oxaliplatin-based or irinotecan-based chemotherapy depending on previous chemotherapy (chemotherapy switch).

Treatment:

Drug: Fruquintinib

Drug: mFOLFOX6

Drug: FOLFIRI