Combining cetuximab and irinotecan for treating advanced colorectal cancer

A Single-arm, Open-label, Phase II Clinical Study of Cetuximab Plus Irinotecan in Patients With NeoRAS Wild-type Metastatic Colorectal Cancer In Third-line Therapy

This study is testing if combining two drugs, cetuximab and irinotecan, can help patients with advanced colorectal cancer who haven't had success with other treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: cetuximab, fruquintinib
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT05962502 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness and safety of cetuximab combined with irinotecan in patients with NeoRAS wild-type metastatic colorectal cancer who have already undergone standard first and second-line therapies. It is a single-arm, open-label phase II trial aimed at patients who have shown progression after previous treatments. The study seeks to determine if this combination can improve outcomes for patients who have limited options left in their treatment journey.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed left-sided metastatic colorectal adenocarcinoma that is NeoRAS wild-type and who have progressed after standard therapies.

Not a fit: Patients with RAS or BRAF mutations or those who have not progressed after standard therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with advanced colorectal cancer who have limited treatment alternatives.

How similar studies have performed: Previous studies have shown promising results with similar combinations, indicating potential efficacy in this patient population.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years.
2. Histologically confirmed colorectal adenocarcinoma.
3. Patients with initial RAS mutant, BRAF wild-type left-sided mCRC.
4. Progression after standard first-line and second-line therapy (previously treated with fluorouracil compounds, oxaliplatin and irinotecan).
5. Tumor progression within 3 months during or after irinotecan-containing regimen.
6. Blood-based ctDNA testing shows that both RAS and BRAF genes are wild-type after second-line therapy progression .
7. There are objectively measurable lesions according to RECIST v1.1 criteria.
8. Normal hematologic function (platelets \> 90 × 109/L; leukocytes \> 3 × 109/L; neutrophils \> 1.5 × 109/L; hemoglobin \> 8.0g/100ml).
9. Serum bilirubin ≤ 1.5 x the upper limit of normal (ULN) and transaminases ≤ 5 x ULN.
10. Normal coagulation function, albumin ≥ 35 g/L.
11. Liver function: Child-Push score: Class A.
12. Serum creatinine \< 1.5 x ULN, or calculated creatinine clearance ≥ 50 ml/min (using the Cockcroft Gault formula).
13. ECOG PS score 0-2.
14. Life expectancy \> 3 months.
15. Sign written informed consent.
16. Willing and able to be followed up until death or end of study or study termination.

Exclusion Criteria:

1. Primary right-sided mCRC.
2. dMMR/MSI-H mCRC.
3. Patients with initial RAS wild-type or BRAF mutant mCRC.
4. ctDNA testing shows that RAS or BRAF gene is mutant mCRC after second-line therapy.
5. Serious arterial embolism or ascites.
6. Serious bleeding tendency or coagulation disorder.
7. Serious uncontrolled systemic complications such as infection or diabetes.
8. Clinically significant cardiovascular disease such as cerebrovascular accident (within 6 months prior to enrollment), myocardial infarction (within 6 months prior to enrollment), uncontrolled hypertension despite appropriate medical treatment. Unstable angina, congestive heart failure (NYHA class 2-4), cardiac arrhythmia requiring medication.
9. History or physical evidence of central nervous system disease (e.g., primary brain tumor, epilepsy uncontrolled by standard of care, any history of brain metastases or stroke).
10. Other malignancies (except cutaneous basal cell carcinoma and/or cervical carcinoma in situ of the cervix and/or thyroid carcinoma after radical surgery) within the past 5 years.
11. Hypersensitivity to any drug in the study.
12. Pregnant and lactating women.
13. Women of childbearing age (\< 2 years after last menstruation) or men of fertile potential who are not using or refuse to use effective non-hormonal contraception (intrauterine contraceptive ring, barrier contraceptives combined with spermicidal gel, or surgical sterilization).
14. Unable or unwilling to comply with the study protocol.
15. Patients with any other diseases, dysfunction caused by metastatic lesions, or suspected disease found by physical examination, indicating possible contraindications to the use of the investigational drug or putting the patients at high risk of treatment-related complications.

Where this trial is running

Guangzhou, Guangdong

• Cancer center of Sun Yat-sen University — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Ruihua Xu, MD, PhD — Sun Yat-sen University
• Study coordinator: Ruihua Xu, MD, PhD

Conditions Metastatic Colorectal Cancer; NeoRAS wild-type; mCRC; Cetuximab; Third-line therapy