Trifluridine/Tipiracil Plus Fruquintinib vs. Trifluridine/Tipiracil Plus Bevacizumab in Refractory Metastatic Colorectal Cancer: A Randomized, Controlled, Open-Label, Non-Inferiority Trial
Overview
- Phase
- Phase 2
- Intervention
- Trifluridine/tipiracil plus fruquintinib
- Conditions
- Not specified
- Sponsor
- Sun Yat-sen University
- Enrollment
- 236
- Locations
- 1
- Primary Endpoint
- PFS
- Status
- Not yet recruiting
- Last Updated
- 5 months ago
Overview
Brief Summary
This study is an investigator-initiated, prospective, multicenter, randomized, controlled, open-label, non-inferiority trial designed to evaluate the efficacy and safety of trifluridine/tipiracil plus fruquintinib versus trifluridine/tipiracil plus bevacizumab in the treatment of refractory metastatic colorectal cancer.
Detailed Description
A total of 236 patients will be enrolled in this investigator-initiated, prospective, multicenter, randomized, controlled, open-label, non-inferiority trial. Experimental group: Trifluridine/tipiracil 35 mg/m² orally twice daily on days 1-5 and 8-12, repeated every 4 weeks, plus fruquintinib 4 mg orally once daily for 3 weeks followed by 1 week off, repeated every 4 weeks. Control group: Trifluridine/tipiracil 35 mg/m² orally twice daily on days 1-5 and 8-12, repeated every 4 weeks, plus bevacizumab 5 mg/kg intravenously on day 1 every 2 weeks.
Investigators
Peng Jian-jun
Professor
Sun Yat-sen University
Eligibility Criteria
Inclusion Criteria
- •All study participants must sign the informed consent form before any study-related procedures are initiated.
- •Aged 18-75 years, both males and females.
- •Histologically confirmed unresectable colorectal cancer.
- •RAS status known (mutant or wild-type).
- •Progression or intolerance after at least two prior systemic regimens that must have contained fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy plus anti-VEGF therapy and/or anti-EGFR therapy.
- •At least one measurable lesion per RECIST v1.
- •Able to swallow oral tablets or capsules.
- •Estimated life expectancy ≥ 12 weeks.
- •ECOG performance status 0-
- •Adequate major organ function (within 7 days before randomization):
Exclusion Criteria
- •1.Prior treatment with trifluridine/tipiracil, fruquintinib, or any other VEGF-receptor tyrosine-kinase inhibitor (e.g., apatinib, regorafenib, anlotinib).
- •2.Pregnant or lactating women, or women who may become pregnant during the study.
- •3.Anti-cancer therapy given ≤ 4 weeks before randomization (or not yet completed).
- •4.Clinically relevant non-haematological CTCAE grade ≥ 3 toxicity from prior anti-cancer therapy that has not resolved to ≤ grade 1 (except alopecia and skin pigmentation).
- •5.Symptomatic central-nervous-system metastases, unstable neurological status, or requirement for an increased steroid dose to control CNS disease.
- •6.Severe or uncontrolled acute or chronic active infection. 7.History of active or interstitial lung disease, pneumonitis, or pulmonary arterial hypertension.
- •8.Clinically significant active hepatitis of any cause, including but not limited to hepatitis B or C.
- •9.Known HIV-positive status. 10.Uncontrolled hypertension (systolic BP ≥ 150 mmHg and/or diastolic BP ≥ 100 mmHg), uncontrolled arrhythmia, or symptomatic arrhythmia.
- •11.Arterial thrombo-embolic event ≤ 6 months before randomization, including cerebrovascular accident or myocardial infarction.
- •12.Major surgery ≤ 4 weeks before randomization (surgical incision must be fully healed before study drug administration), not yet recovered from previous surgery, or major surgery anticipated during the study.
Arms & Interventions
Trifluridine/tipiracil plus fruquintinib
Intervention: Trifluridine/tipiracil plus fruquintinib
Trifluridine/tipiracil plus bevacizumab
Intervention: trifluridine/tipiracil plus bevacizumab
Outcomes
Primary Outcomes
PFS
Time Frame: Time from the date of randomization to the first occurrence of disease progression (as assessed by the investigator according to RECIST v1.1) or death, whichever occurs first,up to 2 years
Progression-free Survival
Secondary Outcomes
- OS(Time from the date of randomization to death from any cause up to 3 years)
- ORR(from randomization up to progressive disease or EOT due to any cause, up to 2 years)
- DCR(from randomization up to progressive disease or EOT due to any cause, up to 2 years)
- Safety and tolerance(from first dose to within 30 days after the last dose)