Evaluating anti-EGFR therapy effectiveness in specific colorectal cancer patients

Predictive Value of Other Oncogene Mutations for Anti-EGFR Monoclonal Antibodies Efficacy in Patients With Left-sided RAS-wild Type Metastatic Colorectal Cancer: Multicenter Randomized Phase III Trial

This study is testing if a personalized treatment approach using anti-EGFR therapy can help people with left-sided RAS-wild type metastatic colorectal cancer do better than standard chemotherapy.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 355 (estimated)
• Ages: 18 Years to 99 Years
• Sex: All
• Sponsor: City Clinical Oncology Hospital No 1 (Government)
• Drugs / interventions: panitumumab, cetuximab, bevacizumab, chemotherapy
• Locations: 3 sites (Moscow and 2 other locations)
• Trial ID: NCT06226857 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy of anti-EGFR therapy in patients with left-sided RAS-wild type metastatic colorectal cancer. Participants will be randomized into two main cohorts: a control group receiving standard chemotherapy with anti-EGFR therapy and an experimental group undergoing extensive molecular profiling to tailor treatment based on genetic variations. The study aims to assess how these different approaches impact treatment outcomes and patient responses. A total of 355 patients will be enrolled, focusing on those who have not previously received systemic therapy for metastatic disease.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with unresectable left-sided metastatic colorectal cancer and verified wild-type KRAS/NRAS/BRAF status.

Not a fit: Patients with resectable tumors or those who have previously received systemic therapy for metastatic disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to more personalized and effective treatment options for patients with metastatic colorectal cancer.

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

Eligibility criteria

Inclusion Criteria:

1. Informed consent signed before commencing any procedures related to the clinical trial.
2. Age ≥18 years.
3. ECOG status 0-2.
4. Life expectancy greater than 12 weeks as assessed by the investigator.
5. Verified diagnosis of colorectal adenocarcinoma (C18.5, C19, C20).
6. Metastatic unresectable form of the disease that has not previously received any systemic therapy for the metastatic process (previous neo-/adjuvant therapy completed at least 6 months before the detection of metastases is allowed).
7. Left-sided localization of the primary tumor (from the splenic flexure of the colon inclusive).
8. Verified wild type KRAS, NRAS determined from tumor tissue.
9. Satisfactory function of hematopoiesis and internal organs:

   * absolute number of neutrophils ≥ 1.5×10 9 /l;
   * platelets ≥ 100×10 9 /l;
   * hemoglobin ≥ 90 g/l.
   * creatinine clearance above 50 ml/min;
   * total bilirubin \<1.5 X the upper limit of normal;
   * ALT or AST \>5 X the upper limit of normal in the presence of liver metastases or \>2.5 X the upper limit of normal in the absence of liver metastases.
10. Availability of a sufficient amount of tumor material for molecular genetic research. Tumor material must be collected no more than 24 months before inclusion in the study.

Exclusion Criteria:

1. Previous systemic therapy for metastatic disease.
2. Presence of KRAS/NRAS/V600E mutations (except for unknown BRAF status).
3. Uncertain KRAS/NRAS status
4. The presence of any other malignant tumor, with the exception of radically treated basal cell carcinoma, cervical cancer in situ, currently or within 5 years before inclusion in the study. Pregnant and lactating women, as well as planning pregnancy during the period of therapy in a clinical trial and 6 months after the end of therapy.
5. HIV infection, active hepatitis B, active hepatitis C.
6. Complicated primary tumor, requiring urgent surgical intervention. After it is eliminated, the patient can participate in the study.
7. The presence of a disease or condition that, in the opinion of the investigator, prevents the patient from participating in the study.
8. Impossibility of organizing central venous access.

Where this trial is running

Moscow and 2 other locations

• Moscow Multidiciplinary Clinical Center Kommunarka — Moscow, Russia (Recruiting)
• N.N Blokhin Cancer Reserch Center — Moscow, Russia (Recruiting)
• Reutov Clinical hospital — Reutov, Russia (Recruiting)

Study contacts

• Study coordinator: Ilya Pokataev, phD

Conditions Colorectal Neoplasms; Chemotherapy Effect; Molecular Sequence Variation