Trifluridine/Tipiracil Plus Fruquintinib vs. Trifluridine/Tipiracil Plus Bevacizumab in Refractory Metastatic Colorectal Cancer: A Randomized, Controlled, Open-Label, Non-Inferiority Trial

NCT07261709 | Not Yet Recruiting Phase 2

• 1 other identifier: TAS-FUR
• Study Type: interventional
• Target: 236
• Locations: 1 country
• Sites: 1

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.

Conditions

Refractory Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• PFS

  Progression-free Survival

  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

Secondary Outcomes (4)

• 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

Study Arms (2)

Trifluridine/tipiracil plus fruquintinib

EXPERIMENTAL

Drug: Trifluridine/tipiracil plus fruquintinib

Trifluridine/tipiracil plus bevacizumab

ACTIVE COMPARATOR

Drug: trifluridine/tipiracil plus bevacizumab

Interventions

trifluridine/tipiracil plus bevacizumab DRUG

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.

Trifluridine/tipiracil plus bevacizumab

Trifluridine/tipiracil plus fruquintinib DRUG

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.

Trifluridine/tipiracil plus fruquintinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 v1.1.
• Able to swallow oral tablets or capsules.
• Estimated life expectancy ≥ 12 weeks.
• ECOG performance status 0-1.
• Adequate major organ function (within 7 days before randomization):
• Absolute neutrophil count ≥ 1.5 × 10⁹/L Platelet count ≥ 75 × 10⁹/L Hemoglobin ≥ 90 g/L (no transfusion within 7 days) Creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula) Total bilirubin ≤ 1.5 × upper limit of normal (ULN) AST and ALT ≤ 2.5 × ULN (≤ 5 × ULN if liver metastases present) Urinalysis showing proteinuria ≤ 1+ or 24-h urine protein \< 1 g INR or PT ≤ 1.5 × ULN (acceptable if on anticoagulation and PT within intended therapeutic range)
• Women of child-bearing potential must have a negative serum pregnancy test within 7 days before randomization; all participants and their partners must agree to use highly effective contraception from screening through at least 6 months after the last dose of study medication.

You may not qualify if:

• Prior treatment with trifluridine/tipiracil, fruquintinib, or any other VEGF-receptor tyrosine-kinase inhibitor (e.g., apatinib, regorafenib, anlotinib).
• Pregnant or lactating women, or women who may become pregnant during the study.
• Anti-cancer therapy given ≤ 4 weeks before randomization (or not yet completed).
• 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).
• Symptomatic central-nervous-system metastases, unstable neurological status, or requirement for an increased steroid dose to control CNS disease.
• Severe or uncontrolled acute or chronic active infection. 7.History of active or interstitial lung disease, pneumonitis, or pulmonary arterial hypertension.
• Clinically significant active hepatitis of any cause, including but not limited to hepatitis B or C.
• Known HIV-positive status. 10.Uncontrolled hypertension (systolic BP ≥ 150 mmHg and/or diastolic BP ≥ 100 mmHg), uncontrolled arrhythmia, or symptomatic arrhythmia.
• Arterial thrombo-embolic event ≤ 6 months before randomization, including cerebrovascular accident or myocardial infarction.
• 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.
• Radiotherapy ≤ 2 weeks before randomization, except short-course palliative radiotherapy for symptom relief.
• Any other clinically significant medical condition that, in the investigator's opinion, would compromise patient safety or study integrity.
• Concurrent or previous malignancy within 5 years, except adequately treated basal-cell or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

the first affiliated hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080

Guangzhou, Guangdong, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Trifluridine; tipiracil; HMPL-013; Bevacizumab

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

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Jianjun Peng

CONTACT

+8613602263939; pjianj@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 21, 2025
• First Posted: December 3, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): March 30, 2028
• Last Updated: December 3, 2025

Record last verified: 2025-10

Locations

CN (1)