ctDNA-Guided Cetuximab or Bevacizumab Plus Trifluridine/Tipiracil in RAS/BRAF Wild-Type mCRC

NCT07012954 | Recruiting Phase 1

• 1 other identifier: RECHALLENGE-CRC
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this randomized controlled clinical trial is to evaluate the efficacy of ctDNA-guided rechallenge with cetuximab plus trifluridine/tipiracil compared with bevacizumab plus trifluridine/tipiracil in patients with treatment-refractory, RAS/BRAF wild-type metastatic colorectal cancer.

Conditions

Colorectal Cancer Metastatic

Keywords

ctDNA profiling; RAS/BRAF wild-type mCRC; cetuximab plus trifluridine/tipiracil; bevacizumab plus trifluridine/tipiracil; rechallenge therapy

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  The percentage of patients in a study group who have a partial or complete response to treatment according to RECIST v1.1 criteria

  Assessed after every 4 cycles (each cycle is 14 days) from treatment initiation until radiographic disease progression, treatment discontinuation, or completion of the 5-year follow-up, whichever occurs first

Secondary Outcomes (3)

• Progression Free Survival

  Assessed throughout the study duration (5 years)

• Overall survival

  Assessed throughout the study duration (5 years)

• Adverse events

  Assessed throughout the study duration (5 years)

Study Arms (2)

cetuximab plus trifluridine/tipiracil

EXPERIMENTAL

Trifluridine/tipiracil 35 mg/m² (orally for 5 days, followed by 9 days off) plus cetuximab 500 mg/m² intravenous drip (IVD) once every two weeks.

Drug: Cetuximab (Erbitux, C225); Drug: trifluridine/tipiracil

bevacizumab plus trifluridine/tipiracil

ACTIVE COMPARATOR

Trifluridine/tipiracil 35 mg/m² (orally for 5 days, followed by 9 days off) plus bevacizumab 5 mg/kg administered by intravenous drip (IVD), repeated every two weeks.

Drug: trifluridine/tipiracil; Drug: Bevacizumab ( Avastin)

Interventions

Cetuximab (Erbitux, C225) DRUG

cetuximab 500 mg/m² repeated every two weeks.

Also known as: Erbitux, C225

cetuximab plus trifluridine/tipiracil

trifluridine/tipiracil DRUG

Trifluridine/tipiracil 35 mg/m² (orally for 5 days, followed by 9 days off)

bevacizumab plus trifluridine/tipiracil; cetuximab plus trifluridine/tipiracil

Bevacizumab ( Avastin) DRUG

bevacizumab 5 mg/kg

bevacizumab plus trifluridine/tipiracil

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed colorectal adenocarcinoma
• Initial RAS/BRAF wild-type status
• Received first-line treatment with FOLFOX, FOLFIRI, or FOLFOXIRI combined with cetuximab, with documented clinical benefit (CR/PR/SD) and progression-free survival (PFS) ≥ 6 months
• Disease progression occurred during or within 3 months after cetuximab-based first-line therapy
• Experienced further tumor progression after receiving second-line or subsequent treatments
• At least 4 months have elapsed since the last administration of cetuximab
• At least one measurable lesion according to RECIST v1.1
• RAS/BRAF wild-type status confirmed by blood-based ctDNA testing
• Normal hematologic function (platelets \> 90 × 10⁹/L; white blood cells \> 3 × 10⁹/L; neutrophils \> 1.5 × 10⁹/L; hemoglobin \> 10.0 g/100 ml)
• Serum bilirubin ≤ 1.5 × upper limit of normal (ULN), transaminases ≤ 5 × ULN
• No ascites, normal coagulation function, serum albumin ≥ 35 g/L
• Child-Pugh class A liver function
• Serum creatinine below ULN or calculated creatinine clearance \> 50 ml/min (using the Cockcroft-Gault formula)
• ECOG performance status of 0-1
• Expected survival \> 3 months

You may not qualify if:

• Presence of RAS or BRAF gene mutations
• Severe arterial embolism or ascites
• Bleeding tendency or coagulation disorders
• Hypertensive crisis or hypertensive encephalopathy
• Severe and uncontrolled systemic complications such as infections or diabetes
• Clinically significant cardiovascular diseases, including cerebrovascular accident (within 6 months prior to enrollment), myocardial infarction (within 6 months prior to enrollment), uncontrolled hypertension despite appropriate medical therapy, unstable angina, congestive heart failure (NYHA class II-IV), or arrhythmias requiring medical treatment History of or physical examination indicating central nervous system diseases (e.g., primary brain tumor, epilepsy not controlled with standard therapy, any brain metastases, or history of stroke)
• History of other malignancies within the past 5 years (excluding adequately treated basal cell carcinoma of the skin, carcinoma in situ of the cervix, and/or thyroid cancer)
• Known allergy to any of the study drugs
• Pregnant or breastfeeding women
• Women of childbearing potential (within 2 years of last menstruation) or men with reproductive potential who are not using or refuse to use effective non-hormonal contraception (e.g., intrauterine device, barrier method with spermicidal gel, or sterilization)
• Inability or unwillingness to comply with the study protocol
• Any other disease, functional impairment caused by metastatic lesions, or suspicious findings on physical examination that may indicate contraindications to study treatment or place the patient at high risk of treatment-related complications

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Interventions

Cetuximab; trifluridine tipiracil drug combination; Bevacizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Deshen Wang, PhD

CONTACT

87342487; wangdsh@sysucc.org.cn

Ruihua Xu, PhD

CONTACT

87342479; xurh@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Prospective, randomized, controlled, multicenter clinical study

Study Record Dates

• First Submitted: May 24, 2025
• First Posted: June 10, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2030
• Last Updated: June 24, 2025

Record last verified: 2025-06

Locations

CN (1)