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Colorectal Cancer MetastaticPhase 1/2NCT07012954

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

A Phase 1/2 study testing Cetuximab (Erbitux, C225), trifluridine/tipiracil and Bevacizumab ( Avastin) in people with Colorectal Cancer Metastatic, run by Sun Yat-sen University at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Colorectal Cancer Metastatic
What is being tested?
Cetuximab (Erbitux, C225), trifluridine/tipiracil and Bevacizumab ( Avastin)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
64 participants
Where
1 siteChina
Study dates
1 Jun 2025to 31 Dec 2030
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Signed written informed consent
  • Willing and able to undergo follow-up until death, study completion, or study termination

Who cannot join

  • 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)
Show all 12Show fewer
  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Deshen Wang, PhD contact

87342487 ext. 020

wangdsh@sysucc.org.cn

Ruihua Xu, PhD contact

87342479 ext. 020

xurh@sysucc.org.cn

China1 site, 1 recruiting

  • Sun Yat-sen University Cancer Center

    Guangzhou, Guangdong, 510060

    Deshen Wang, PhD, 87342487 ext. 020, wangdsh@sysucc.org.cn

    Recruiting

Other trials in China

About this study

Official title: ctDNA-Guided Rechallenge With Cetuximab Plus Trifluridine/Tipiracil Versus Bevacizumab Plus Trifluridine/Tipiracil for RAS/BRAF Wild-Type Refractory Metastatic Colorectal Cancer: A Randomized Clinical Trial

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.

Read the detailed description

Colorectal cancer (CRC) remains a major public health challenge in China, where its incidence and mortality continue to rise. Although surgical resection is the cornerstone of curative treatment, metastatic disease develops in 30-40% of patients. Anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies such as cetuximab and panitumumab are pivotal therapeutic agents for patients with RAS wild-type metastatic colorectal cancer (mCRC), exerting antitumor effects through inhibition of the EGFR pathway and activation of antibody-dependent cell-mediated cytotoxicity.

Recent evidence from phase II trials and retrospective analyses has suggested that rechallenge with anti-EGFR monoclonal antibodies in later-line settings may confer clinical benefit in selected patients who previously responded to first-line anti-EGFR-based therapy. Studies such as CRICKET and CHRONOS have highlighted the feasibility of this approach, with emerging data supporting the utility of circulating tumor DNA (ctDNA) to guide patient selection based on RAS, BRAF, and EGFR extracellular domain mutation status. Notably, the VELO study demonstrated improved progression-free survival (PFS) with third line panitumumab plus trifluridine/tipiracil compared to trifluridine/tipiracil alone, particularly in patients with ctDNA-confirmed RAS/BRAF wild-type status. Similarly, the ongoing PARERE and recently reported CITRIC studies have further emphasized the value of molecular stratification using liquid biopsy to refine anti-EGFR rechallenge strategies and optimize treatment sequencing.

The current study builds upon these findings and aims to evaluate and compare the efficacy and safety of cetuximab plus trifluridine/tipiracil versus bevacizumab plus trifluridine/tipiracil as later-line treatments in Chinese patients with RAS/BRAF wild-type mCRC, with treatment selection informed by ctDNA profiling. By integrating real-world clinical data and contemporary molecular diagnostics, this study seeks to assess the potential benefit of cetuximab-based rechallenge therapy in a population with limited therapeutic options and to contribute further evidence supporting the implementation of personalized, biomarker-guided strategies in later-line mCRC management.

Being tested
Cetuximab (Erbitux, C225), trifluridine/tipiracil, Bevacizumab ( Avastin)
Keywords
ctDNA profiling, RAS/BRAF wild-type mCRC, cetuximab plus trifluridine/tipiracil, bevacizumab plus trifluridine/tipiracil, rechallenge therapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cetuximab (Erbitux, C225)Drug

    Also called Erbitux, C225

    cetuximab 500 mg/m² repeated every two weeks.

  • trifluridine/tipiracilDrug

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

  • Bevacizumab ( Avastin)Drug

    bevacizumab 5 mg/kg

Study groups in NCT07012954
Study groupRoleWhat they receive
cetuximab plus trifluridine/tipiracilExperimentalTrifluridine/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.
Receives: Drug: Cetuximab (Erbitux, C225); Drug: trifluridine/tipiracil
bevacizumab plus trifluridine/tipiracilActive comparatorTrifluridine/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.
Receives: Drug: trifluridine/tipiracil; Drug: Bevacizumab ( Avastin)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 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)

  1. Progression Free Survival

    The proportion of patients who remain alive and whose disease does not progress after starting treatment

    Measured: Assessed throughout the study duration (5 years)

  2. Overall survival

    Time from treatment initiation to death from any cause or censored due to loss to follow up

    Measured: Assessed throughout the study duration (5 years)

  3. Adverse events

    Assessment of adverse events and their severity according to NCI CTCAE version 5.0 criteria

    Measured: Assessed throughout the study duration (5 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jun 2025
  2. Study start1 Jun 2025
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 Dec 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Prospective, randomized, controlled, multicenter clinical study
Masking
None (open label)
Enrolment
64 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07012954
Sponsor's protocol ID
RECHALLENGE-CRC
Status last verified
Jun 2025
First submitted
24 May 2025
Last updated
24 Jun 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: Data and materials used in this study can be made available following study completion upon reasonable request to the corresponding author, subject to ethical and legal considerations and applicable data-sharing agreements.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cetuximab (Erbitux, C225), trifluridine/tipiracil and Bevacizumab ( Avastin) in people with Colorectal Cancer Metastatic, run by Sun Yat-sen University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 24 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Deshen Wang, PhD (87342487 ext. 020, wangdsh@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07012954.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2025.

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