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

Metastatic Colorectal Cancer Clinical Trial

— EmutRAS  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03908788
• Other study ID #: 2018-A00232-53
• Status: Active, not recruiting
• Phase: N/A
• Start date: July 26, 2018
• Est. completion date: October 2025

Study information

• Verified date: May 2024
• Source: Institut du Cancer de Montpellier - Val d'Aurelle
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 130
• Est. completion date: October 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Device:
• Intplex test
Blood sample at each tumor assessment

Locations

Country	Name	City	State
France	ICM Val d'Aurelle	Montpellier
France	Institut du Cancer de Montpellier - Val d'Aurelle	Montpellier

Sponsors (1)

Lead Sponsor	Collaborator
Institut du Cancer de Montpellier - Val d'Aurelle

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Proportion of patients with a BRAF mutation under anti-EGFR therapy	From baseline to the end of treatment	Approximately 8 weeks
Secondary	Progression-free survival	From baseline to the database cutoff	Approximately 36 months
Secondary	Global survival	From baseline to the database cutoff	Approximately 36 months
Secondary	Evaluation of the following criterion: total concentration of circulating DNA	From baseline to the end of treatment	Approximately 8 weeks
Secondary	Evaluation of the following criterion: integrity index	From baseline to the end of treatment	Approximately 8 weeks
Secondary	Evaluation of the following criterion: concentration of mutated alleles	From baseline to the end of treatment	Approximately 8 weeks
Secondary	Evaluation of the following criterion: frequency of mutated alleles	From baseline to the end of treatment	Approximately 8 weeks