Trifluridine/Tipiracil Plus Regorafenib vs Trifluridine/Tipiracil Plus Bevacizumab for Refractory Metastatic Colorectal Cancer

NCT06992648 | Recruiting Phase 3

• 1 other identifier: 2024-1454
• Study Type: interventional
• Target: 302
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to demonstrate the non-inferiority of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in terms of progression free survival in patients with refractory metastatic colorectal cancer(mCRC) patients. It will also try to estimate the effect of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in terms of OS, ORR, and DCR in patients with refractory mCRC. Other secondary objectives are to compare the safety and tolerance, and the impact on QoL of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in patients with refractory mCRC.

Conditions

Colorectal Cancer Metastatic; Colorectal Cancer Recurrent

Keywords

trifluridine/tipiracil; regorafenib; bevacizumab; non-inferiority; refractory metastatic colorectal cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  The primary objective is to demonstrate the non-inferiority of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in terms of PFS in patients with refractory mCRC

  up to 24 months

Secondary Outcomes (3)

• Overall survival (OS)

  up to 36 months

• Objective Response Rate（ORR）

  up to 36 months

• Disease Control Rate（DCR）

  up to 36 months

Other Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  up to 36 months

Study Arms (2)

experimental arm

EXPERIMENTAL

Trifluridine/tipiracil will be administered orally BID at a starting dose of 30 mg per square meter of body-surface area, on days 1 through 5 every 2 weeks. Regorafenib will be administered orally QD at a dose-escalation strategy (80 mg/day, followed by weekly increase of 40 mg to 120 mg/day), if no significant drug-related adverse events occurred and 120 mg/day for 21 days of a 28-day cycle.

Drug: Trifluridine/Tipiracil + Regorafenib

Control arm

ACTIVE COMPARATOR

Trifluridine/tipiracil will be administered orally BID at a starting dose of 35 mg per square meter of body-surface area, on days 1 through 5 every 2 weeks. Bevacizumab, at a dose of 5 mg per kilogram of body weight, will be administered IV every 2 weeks (day 1 and day 15).

Drug: Trifluridine/tipiracil + bevacizumab

Interventions

Trifluridine/Tipiracil + Regorafenib DRUG

Trifluridine/tipiracil will be administered orally BID at a starting dose of 30 mg per square meter of body-surface area, on days 1 through 5 every 2 weeks. Regorafenib will be administered orally QD at a dose-escalation strategy (80 mg/day, followed by weekly increase of 40 mg to 120 mg/day), if no significant drug-related adverse events occurred and 120 mg/day for 21 days of a 28-day cycle.

experimental arm

Trifluridine/tipiracil + bevacizumab DRUG

Trifluridine/tipiracil will be administered orally BID at a starting dose of 35 mg per square meter of body-surface area, on days 1 through 5 every 2 weeks. Bevacizumab, at a dose of 5 mg per kilogram of body weight, will be administered IV every 2 weeks (day 1 and day 15).

Control arm

Eligibility Criteria

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

You may qualify if:

• Sign Informed Consent Form (ICF) must be obtained during the screening visit, prior to the performance of any study procedure；
• Male or female patient aged ≥18 years old;
• Has histologically confirmed unresectable adenocarcinoma of the colon or rectum (all other histological types are excluded);
• RAS status must have been previously determined (mutant or wild-type) based on local assessment of tumor biopsy;
• Prior treatment regimens for the treatment of advanced colorectal cancer must have included a fluoropyrimidine, irinotecan, oxaliplatin, an anti-VEGF monoclonal antibody and/or an anti-EGFR monoclonal antibody for RAS wildtype patients;
• Has measurable or non-measurable disease as defined by RECIST version 1.1;
• Is able to swallow oral tablets;
• Estimated life expectancy ≥12 weeks;
• ECOG PS 0-1；
• Has adequate organ function as defined by the following laboratory values obtained within 7 days prior to randomization:
• Absolute neutrophil count ≥1.5×109/L; Platelet count ≥75×109/L; Hemoglobin≥90g/L (7 days without transfusion); Creatinine clearance ≥60 mL/min, assessed using the Cockcroft \& Gault formula; Total serum bilirubin \<1.5×upper limit of normal (ULN) (unless Gilbert disease confirmed); Aspartate aminotransferase (AST; SGOT) and alanine aminotransferase (ALT; SGPT) ≤ 2.5×ULN (unless if liver function abnormalities are due to underlying liver metastasis, AST (SGOT) and ALT (SGPT) ≤ 5×ULN); Urine protein \<1+ on urinalysis or 24-hour urine protein \<1g; International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5×ULN (For patients receiving anti-coagulant therapy the adequate therapeutic levels of PT should be confirmed).
• Female of childbearing potential must have been tested negative in a serum pregnancy test within 7 days prior to randomization; All patients must agree to use a highly effective method of birth control as well as their partners during the study and lasting at least 6 months after the last dose.

You may not qualify if:

• Prior trifluridine/tipiracil or TKI regimens for the treatment of advanced colorectal cancer;
• Pregnancy, lactating female or possibility of becoming pregnant during the study;
• Patients currently receiving or having received anticancer therapies within 4 weeks prior to randomization;
• Has not recovered from clinically relevant non-hematologic CTCAE grade ≥ 3 toxicity of previous anticancer therapy prior to randomization (excluding alopecia, and skin pigmentation);
• Has symptomatic central nervous system metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease;
• Has severe or uncontrolled active acute or chronic infection;
• Has active or history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension;
• Has any clinically significant active hepatitis, including but not limited to Hepatitis B or Hepatitis C Virus infection;
• Known carriers of HIV antibodies;
• Confirmed uncontrolled arterial hypertension (defined as systolic blood pressure ≥ 150 mm Hg and/or diastolic blood pressure ≥ 100 mm Hg) or uncontrolled or symptomatic arrhythmia;
• Deep arterial thromboembolic events including cerebrovascular accident or myocardial infarction within the last 6 months prior to randomization;
• Major surgery within 4 weeks prior to randomization (the surgical incision should be fully healed prior to study drug administration), or has not recovered from side effects of previous surgery, or patient that may require major surgery during the study;
• Prior radiotherapy if completed less than 2 weeks before randomization, except if provided as a short course for symptoms palliation only;
• Other clinically significant medical conditions; Other malignancies.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

The Second Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Trifluridine; tipiracil; regorafenib; 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

Study Officials

• Ying Yuan, Prof.

  Second Affiliated Hospital, School of Medicine, Zhejiang University

  PRINCIPAL INVESTIGATOR

• Jing Hao, Prof.

  Qilu Hospital of Shandong University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yinuo TAN, Dr.

CONTACT

+86-13805753262; tan0yi0nuo@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2025
• First Posted: May 28, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: May 28, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)