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

Metastatic Colorectal Cancer Clinical Trial

Official title:

The Efficacy and Safety of Fruquintinib Combined With FOLFIRI/FOLFOX as Second-line Treatment in Patients With RAS-mutant Metastatic Colorectal Cancer: A Single-center, Open-label, Single-arm Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05634590
• Other study ID #: HMPL-013-FLAG-C119
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: December 2022
• Est. completion date: December 2025

Study information

• Verified date: November 2022
• Source: Fudan University
• Contact: Ye Xu, PhD
• Phone: +86-21-6417-5590
• Email: xu_shirley021[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 68
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Fruquintinib
4mg, orally, once daily, 3 weeks on/ 1 week off
• 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
• 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

Locations

Country	Name	City	State
China	Department of Colorectal Surgery Fudan University Shanghai Caner Center	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)	time from enrollment to the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator	assessed up to 1 year
Secondary	Objective response rate (ORR)	the proportion of patients with complete response or partial response, using RECIST v 1.1.	assessed up to 1 year
Secondary	Disease Control Rate (DCR)	the proportion of patients with complete response, partial response or stable disease, using RECIST v 1.1.	assessed up to 1 year
Secondary	Overall survival (OS)	time from randomization to death from any cause.	assessed up to 2 year