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

Phase 2
Not yet recruiting
Conditions
Metastatic Colorectal Cancer
Interventions
Drug: FOLFIRI
Drug: mFOLFOX6
Registration Number
NCT05634590
Lead Sponsor
Fudan University
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).

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
68
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Fruquintinib plus FOLFIRI/FOLFOXFOLFIRIPatients will receive fruquintinib plus FOLFIRI/FOLFOX. Oxaliplatin-based or irinotecan-based chemotherapy depending on previous chemotherapy (chemotherapy switch).
Fruquintinib plus FOLFIRI/FOLFOXmFOLFOX6Patients will receive fruquintinib plus FOLFIRI/FOLFOX. Oxaliplatin-based or irinotecan-based chemotherapy depending on previous chemotherapy (chemotherapy switch).
Fruquintinib plus FOLFIRI/FOLFOXFruquintinibPatients will receive fruquintinib plus FOLFIRI/FOLFOX. Oxaliplatin-based or irinotecan-based chemotherapy depending on previous chemotherapy (chemotherapy switch).
Primary Outcome Measures
NameTimeMethod
Progression-Free Survival (PFS)assessed up to 1 year

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

Secondary Outcome Measures
NameTimeMethod
Objective response rate (ORR)assessed up to 1 year

the proportion of patients with complete response or partial response, using RECIST v 1.1.

Disease Control Rate (DCR)assessed up to 1 year

the proportion of patients with complete response, partial response or stable disease, using RECIST v 1.1.

Overall survival (OS)assessed up to 2 year

time from randomization to death from any cause.

Trial Locations

Locations (1)

Department of Colorectal Surgery Fudan University Shanghai Caner Center

🇨🇳

Shanghai, Shanghai, China

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