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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: Fruquintinib; Drug: FOLFIRI; Drug: mFOLFOX6

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).

• Study Type: Interventional
• Enrollment (Anticipated): 68
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ye Xu, PhD; Phone Number: +86-21-6417-5590; Email: xu_shirley021@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Department of Colorectal Surgery Fudan University Shanghai Caner Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	the proportion of patients with complete response or partial response, using RECIST v 1.1.	assessed up to 1 year
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
Overall survival (OS)	time from randomization to death from any cause.	assessed up to 2 year

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2022
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: November 23, 2022
• First Submitted That Met QC Criteria: November 23, 2022
• First Posted (Actual): December 2, 2022

Study Record Updates

• Last Update Posted (Actual): December 2, 2022
• Last Update Submitted That Met QC Criteria: November 23, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: RAS mutation; Fruquintinib plus Chemotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: HMPL-013-FLAG-C119

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No