Using cetuximab to treat colorectal cancer with liver metastases

Cetuximab as Salvage Therapy in Patients With Neo Wild-type RAS/RAF Metastatic Colorectal Cancer With Liver Metastases. A Proof-of-concept Study

This study is testing if the drug cetuximab, alone or with another drug called irinotecan, can help people with advanced colorectal cancer that has spread to the liver after previous treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 72 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hôpital Franco-Britannique-Fondation Cognacq-Jay (Academic / other)
• Drugs / interventions: bevacizumab, cetuximab
• Locations: 1 site (Levallois-Perret)
• Trial ID: NCT04189055 on ClinicalTrials.gov

What this trial studies

This study investigates the effectiveness of cetuximab, either alone or in combination with irinotecan, in patients with neo wild-type RAS/RAF metastatic colorectal cancer who have previously undergone treatment. Patients will be divided into two cohorts, with cohort #1 receiving cetuximab alone and cohort #2 receiving cetuximab with irinotecan, depending on the results from cohort #1. The study aims to assess the response rate, progression-free survival, overall survival, and safety of the treatment using liquid biopsies for RAS molecular assessment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with unresectable metastatic colorectal cancer that has wild-type RAS mutations.

Not a fit: Patients with RAS mutant colorectal cancer or those who have not previously received 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 previously treated metastatic colorectal cancer.

How similar studies have performed: Other studies have shown promising results with anti-EGFR therapies in similar patient populations, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Provision of signed and dated informed consent and stated willingness to comply with all study procedures and availability for the duration of the study,
2. Male or female subjects, ≥18 years of age,
3. ECOG performance status (ECOG PS, Appendix 15.1) ≤2,
4. Unresectable metastatic RAS mutant (either KRAS or NRAS tumor gene mutation) colorectal cancer,
5. At least one (≥1) measurable and/or evaluable liver metastasis,
6. Prior therapy (resistant or intolerant) with fluoropyrimidines, oxaliplatin, irinotecan and antiangiogenic agent (ie, bevacizumab and/or aflibercept),
7. Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment:

   Hematological status: neutrophils (ANC) ≥1.5x109/L; platelets ≥100x109/L; haemoglobin ≥9g/dL Adequate renal function: serum creatinine clearance (MDRD) ≥ 50 mL/min/1,73 m2 Adequate liver function: serum bilirubin ≤1.5x upper normal limit (ULN), alkaline phosphatase \<5xULN, AST and ALT ≤5xULN, Adequate serum electrolyte levels (magnesium, potassium, calcium) prior to initiation of study treatment,
8. Negative pregnancy test within 7 days prior to initiation of the study drug for female patients of childbearing potential,
9. Effective contraception for both male and female subjects if the risk of conception exists
10. Registration in a national health care system.

Exclusion Criteria:

1. Known allergy or hypersensitivity reactions to any study drug,
2. Women who are pregnant or breastfeeding,
3. Inability to comply with study and follow-up procedures as judged by the Investigator,
4. Patient with BRAF mutant colorectal cancer
5. History of interstitial lung disease
6. Treatment with strong CYP3A4-enzyme inducers such as anticonvulsants (phenytoin, phenobarbital or carbamazepine), rifampin, rifabutin and St. John's wort for patients of cohort #2
7. Treatment with strong CYP3A4-enzyme inhibitors (e.g. grapefruit juice, clarithromycin, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole) for patients of cohort #2
8. Treatment with strong UGT1A inhibitors (e.g. atazanavir, gemfibrozil, indinavir) for patients of cohort # 2
9. Patients of cohort #2 with known UGT1A deficiency
10. Uncontrolled illness, including but not limited to ongoing bacterial, viral or fungal infection requiring systemic therapy, metabolic dysfunction, physical examination/ clinical laboratory finding that leads to a reasonable suspicion of a disease/condition that contraindicates the use of any of investigational drugs that may affect the interpretation of the results, or that may render the subject at high risk of treatment complications.
11. Patient with current intestinal obstruction or history of chronic inflammatory bowel disease
12. Subjects under guardianship, curatorship or judicial protection

Where this trial is running

Levallois-Perret

• Franco-British Hospital - GCS IHFB Cognacq-Jay — Levallois-Perret, France (Recruiting)

Study contacts

• Principal investigator: Benoist CHIBAUDEL, MD — Franco-British Hospital - GCS IHFB Cognacq-Jay
• Study coordinator: Benoist CHIBAUDEL, MD

Conditions Cancer Colorectal; Liver metastasis; KRAS; NRAS