Cetuximab as Salvage Therapy in Patients With Neo Wild-type RAS/RAF Metastatic Colorectal Cancer With Liver Metastases. — CETIDYL  

Cancer Colorectal Clinical Trial

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

Status Recruiting

Clinical Trial Summary

The purpose of this study is to investigate the efficacy of cetuximab or cetuximab-irinotecan in patients with neo wild-type colorectal cancer who have been previously treated for metastatic disease.

Patients will be included in cohort #1 or cohort #2. The inclusion in cohort #2 will start when the results of the cohort #1 are available.

Patient will receive either cetuximab alone (cohort #1) or cetuximab with irinotecan (cohort #2).

Clinical Trial Description

Background - Rationale

KRAS and NRAS mutations are present in roughly 50% of patients with advanced colorectal cancer and predict failure of anti-EGFR mabs therapies, thus genotyping colorectal cancer (CRC) is mandatory for personalized treatments.

Research has been selectively concentrated on the emergence of resistant clones in the blood of patients with wild-type (WT) RAS CRC as biomarker of anti-EGFR therapy resistance.

It has been suggested that patients with metastatic CRC harboring mutated primary tumors, thus not candidate to EGFR inhibitors, frequently have WT RAS circulating tumor cells in blood. Preliminary data suggest that patients with mutant KRAS colon cancer can frequently (50%) switch to a prevalent WT KRAS disease in course of treatment with anti-angiogenic drugs.

In patients with RAS wild-type colorectal cancer who previously received standard therapies, anti-EGFR mabs achieve a response rate of 20% as monotherapy and 30-40% in combination with irinotecan.

The aim of this study is to evaluate the efficacy of cetuximab in patients with pretreated neo wild-type colorectal cancer using liquid biopsies for RAS molecular assessment

Study Objectives

Primary:

• To evaluate the response rate using RECIST 1.1

Secondary:

• To evaluate progression-free survival (PFS), overall survival (OS)

• To evaluate disease control rate (DCR)

• To evaluate safety

Exploratory:

• Frequency of neo wild-type tumors

• Frequency of RAS and BRAF neomutations during treatment

Study Design Prospective multicentric single-arm open-label phase II study in to 2 successive patient cohorts (cohort #1 followed by cohort #2).

Molecular screening using Idylla™ (Biocartis) ctKRAS and ctNRAS/BRAF Mutation Assays.

Cohort #1: Patients will be treated with cetuximab monotherapy (cetuximab 500mg/m² IV, day 1).

Cohort #2: Patients will be treated with cetuximab and irinotecan (cetuximab 500mg/m² IV, day 1; irinotecan 180mg/m² IV, day 1).

In both cohorts, treatment will be given intravenously every 14 days (q2w) until disease progression or limiting toxicity. Tumor evaluations will be done with CT-scan (or MRI) every 8 weeks using RECIST v1.1. ;

Related Conditions & MeSH terms

• Cancer Colorectal
• Neoplasm Metastasis

• NCT number: NCT04189055
• Study type: Interventional
• Source: GCS IHFB Cognacq-Jay
• Contact: Benoist CHIBAUDEL, MD
• Phone: 0147595965
• Email: benoist.chibaudel@ihfb.org
• Status: Recruiting
• Phase: Phase 2
• Start date: January 7, 2020
• Completion date: July 2024