Detection of the Emergence of RAS (Rat Sarcoma Viral Oncogene Homolog) Mutations in Circulating DNA (Deoxyribonucleic Acid) in Patients With mCRC (Metastatic Colorectal Cancer) During Treatment With Anti-EGFR (Epidermal Growth Factor Receptor) Therapy (EmutRAS)

Detection of the Emergence of RAS (Rat Sarcoma Viral Oncogene Homolog) Mutations in Circulating DNA (Deoxyribonucleic Acid) in Patients With Metastatic Colorectal Cancer During Treatment With Anti-EGFR (Epidermal Growth Factor Receptor) Therapy

The analysis of circulating DNA (Deoxyribonucleic acid) to identify potential resistance mechanisms during anti-EGFR (epidermal growth factor receptor) treatment is of great interest, as evidenced by the recent journal published by Corcoran in the prestigious New England Journal of Medicine.

EmutRAS is one of the first studies that will specifically and prospectively evaluate the RAS mutational switch and its impact on the efficiency of the 1st line processing.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Device: Intplex test

Detailed Description

The primary study objective is the Detection of RAS mutational (rat sarcoma viral oncogene homolog) "switch" in circulating DNA by Intplex® test in mCRC (metastatic colorectal cancer) patients treated with antibody anti-EGFR (epidermal growth factor receptor), cetuximab or panitumumab in first line.

The treatment and these modalities will be decided by the investigator.

The study is based on blood sampling, the frequency of which is described below, rhythm of plasma samples:

Inclusion after determination of wild status RAS tissues.

First sampling of 2 EDTA (ethylenediaminetetraacetic acid) tubes, then at each tumour evaluation during treatment with anti EGFR (epidermal growth facor receptor), every 4 cures. At the end of treatment or after more than 36 treatment cures, a final sample will be taken.

No results of the samples will be communicated to the investigator, the sponsor will centralize these results for the final analysis of the study.

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Thibault MAZARD, Dr; Phone Number: +33 0467613000; Email: thibault.mazard@icm.unicancer.fr

Study Locations

• France
  • Montpellier, France, 34298
    • ICM Val D'Aurelle
  • Montpellier, France, 34298
    • Institut du Cancer de Montpellier - Val d'Aurelle

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient with histologically confirmed metastatic colorectal cancer
• Patient treated in the first line by one of the treatments below and according to a bi-monthly schema for cetuximab: FOLFIRI (elvorin + 5 Fluorouracil + irinotecan) ou FOLFOX (elvorin + 5 Fluorouracil + oxalplatin) + Cetuximab* (Erbitux) ; FOLFIRI ou FOLFOX + Panitumumab (Vectibix); FOLFIRINOX ou FOLFOXIRI ((elvorin + 5 Fluorouracil + oxaliplatin + irinotecan) + Cetuximab* (Erbitux); FOLFIRINOX ou FOLFOXIRI + Panitumumab (Vectibix) For patient treated cetuximab administration will be bi-monthly
• Patient with at least one evaluable metastatic target according to RECIST 1.1 (Response Evaluation Criteria in Solid Tumors)
• Wild RAS (rat sarcoma viral oncogene homolog) status detected by standard tissue test, on primary tumor and / or metastasis
• Wild BRAF (murine sarcoma viral oncogene homolog B) status detected by standard tissue test, on primary tumor and / or metastasis
• Man or woman> 18 years old
• Signed informed consent before any specific procedure to study
• Patient affiliated to the social security or equivalent

Exclusion Criteria:

• Previous treatment with an anti-EGFR (epidermal growth factor receptor)
• Patient with a multifocal primary tumor
• RAS (rat sarcoma viral oncogene homolog) status mutated or not detectable on tissue analysis
• BRAF (murine sarcoma viral oncogene homolog B) status mutated or undetectable on tissue analysis
• Patient receiving adjuvant chemotherapy or radiotherapy within <14 days
• History of other cancer in the last 5 years (except in-situ carcinoma of the cervix and cutaneous carcinoma excluding melanoma treated optimally)
• Blood transfusion (whole blood, red blood cell, platelets...) in the previous week
• Patients with psychological, familial, sociological or geographic conditions potentially not favorable to the good observance of the study protocol and the follow-up
• Legal incapacity or limited legal capacity

Participation in another interventional clinical trial - biomedical research (therapeutic strategy type) is not excluded provided that it is use an Anti-EGFR with a AMM (marketing authorization), (Cetuximab - Panitumumab) with a dose and a standard administration rhythm (according to the AMM).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intplex test; In vitro diagnostic device	Device: Intplex test; Blood sample at each tumor assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with mCRC (metastatic colorectal cancer) who develop a RAS (rat sarcoma viral oncogene homolog) mutation under anti-EGFR (epidermal growth factor receptor) therapy	From baseline to the end of treatment	Approximately 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Probability of obtaining a positive test, i.e. RAS status mutated by the Intplex® test, among the patients determined RAS mutated by the tissue test	From baseline to the end of treatment	Approximately 8 weeks
Probability of obtaining a negative test, i.e. wild RAS status by the Intplex® test among patients determined wild RAS by the tissue test	From baseline to the end of treatment	Approximately 8 weeks
Probability of obtaining a positive test, i.e. BRAF status mutated by the Intplex® test, among the patients determined BRAF mutated by the tissue test	From baseline to the end of treatment	Approximately 8 weeks
Probability of obtaining a negative test, i.e. wild BRAF status by Intplex® test among patients determined wild BRAF by tissue test.compared to the pre-treatment tissue test	From baseline to the end of treatment	Approximately 8 weeks
Proportion of patients with a BRAF mutation under anti-EGFR therapy	From baseline to the end of treatment	Approximately 8 weeks
Progression-free survival	From baseline to the database cutoff	Approximately 36 months
Global survival	From baseline to the database cutoff	Approximately 36 months
Evaluation of the following criterion: total concentration of circulating DNA	From baseline to the end of treatment	Approximately 8 weeks
Evaluation of the following criterion: integrity index	From baseline to the end of treatment	Approximately 8 weeks
Evaluation of the following criterion: concentration of mutated alleles	From baseline to the end of treatment	Approximately 8 weeks
Evaluation of the following criterion: frequency of mutated alleles	From baseline to the end of treatment	Approximately 8 weeks

Collaborators and Investigators

• Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2018
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: January 25, 2019
• First Submitted That Met QC Criteria: April 8, 2019
• First Posted (Actual): April 9, 2019

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Metastatic Colorectal Cancer; Detection of the emergence of RAS mutations; Circulating DNA in patients; Treatment with anti-EGFR therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 2018-A00232-53

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No