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

NCT05634590 | Unknown Phase 2

• 1 other identifier: HMPL-013-FLAG-C119
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Colorectal Cancer

Keywords

Fruquintinib plus Chemotherapy; RAS mutation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Objective response rate (ORR)

  assessed up to 1 year

• Disease Control Rate (DCR)

  assessed up to 1 year

• Overall survival (OS)

  assessed up to 2 year

Study Arms (1)

Fruquintinib plus FOLFIRI/FOLFOX

EXPERIMENTAL

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

Drug: Fruquintinib; Drug: FOLFIRI; Drug: mFOLFOX6

Interventions

Fruquintinib DRUG

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

Fruquintinib plus FOLFIRI/FOLFOX

FOLFIRI 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

Fruquintinib plus FOLFIRI/FOLFOX

mFOLFOX6 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

Fruquintinib plus FOLFIRI/FOLFOX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Department of Colorectal Surgery Fudan University Shanghai Caner Center

Shanghai, Shanghai Municipality, 200032, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

HMPL-013; IFL protocol

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Ye Xu, PhD

CONTACT

+86-21-6417-5590; xu_shirley021@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Chief of Department of Colorectal Surgery

Study Record Dates

• First Submitted: November 23, 2022
• First Posted: December 2, 2022
• Study Start: December 1, 2022
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: December 2, 2022

Record last verified: 2022-11

Locations

CN (1)