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

NCT ID: NCT05634590

Last Updated: 2022-12-02

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-31
• Study Completion Date: 2025-12-31

Brief Summary

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.

Detailed 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).

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fruquintinib plus FOLFIRI/FOLFOX

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

Group Type: EXPERIMENTAL

Fruquintinib

Intervention Type: DRUG

4mg, orally, once daily, 3 weeks on/ 1 week off

FOLFIRI

Intervention Type: DRUG

Irinotecan 180 mg/m2, and LV 400 mg/m2 followed by bolus 5-fluorouracil 400mg/m2 and a 46-48h continuous infusion 2400mg/m2 5-fluorouracil on day 1, q2w

mFOLFOX6

Intervention Type: DRUG

Oxaliplatin 85 mg/m2, and LV 400 mg/m2 followed by bolus 5-fluorouracil 400mg/m2 and a 46-48h continuous infusion 2400mg/m2 5-fluorouracil on day 1, q2w

Interventions

Fruquintinib

4mg, orally, once daily, 3 weeks on/ 1 week off

Intervention Type: DRUG

FOLFIRI

Irinotecan 180 mg/m2, and LV 400 mg/m2 followed by bolus 5-fluorouracil 400mg/m2 and a 46-48h continuous infusion 2400mg/m2 5-fluorouracil on day 1, q2w

Intervention Type: DRUG

mFOLFOX6

Oxaliplatin 85 mg/m2, and LV 400 mg/m2 followed by bolus 5-fluorouracil 400mg/m2 and a 46-48h continuous infusion 2400mg/m2 5-fluorouracil on day 1, q2w

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Ye Xu

Professor, Chief of Department of Colorectal Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Department of Colorectal Surgery Fudan University Shanghai Caner Center

Shanghai, Shanghai Municipality, China

Countries

China

Central Contacts

Ye Xu, PhD

Role: CONTACT

xu_shirley021@163.com

+86-21-6417-5590

Other Identifiers

HMPL-013-FLAG-C119

Identifier Type: -

Identifier Source: org_study_id