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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)

Primary Purpose

Metastatic Colorectal Cancer

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Intplex test
Sponsored by
Institut du Cancer de Montpellier - Val d'Aurelle
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Metastatic Colorectal Cancer focused on measuring Metastatic Colorectal Cancer, Detection of the emergence of RAS mutations, Circulating DNA in patients, Treatment with anti-EGFR therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • ICM Val d'AurelleRecruiting
  • Institut du Cancer de Montpellier - Val d'AurelleRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intplex test

Arm Description

In vitro diagnostic device

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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
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
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
Proportion of patients with a BRAF mutation under anti-EGFR therapy
From baseline to the end of treatment
Progression-free survival
From baseline to the database cutoff
Global survival
From baseline to the database cutoff
Evaluation of the following criterion: total concentration of circulating DNA
From baseline to the end of treatment
Evaluation of the following criterion: integrity index
From baseline to the end of treatment
Evaluation of the following criterion: concentration of mutated alleles
From baseline to the end of treatment
Evaluation of the following criterion: frequency of mutated alleles
From baseline to the end of treatment

Full Information

First Posted
January 25, 2019
Last Updated
January 2, 2022
Sponsor
Institut du Cancer de Montpellier - Val d'Aurelle
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1. Study Identification

Unique Protocol Identification Number
NCT03908788
Brief Title
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
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 26, 2018 (Actual)
Primary Completion Date
December 2022 (Anticipated)
Study Completion Date
October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut du Cancer de Montpellier - Val d'Aurelle

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
Metastatic Colorectal Cancer, Detection of the emergence of RAS mutations, Circulating DNA in patients, Treatment with anti-EGFR therapy

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
130 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intplex test
Arm Type
Experimental
Arm Description
In vitro diagnostic device
Intervention Type
Device
Intervention Name(s)
Intplex test
Intervention Description
Blood sample at each tumor assessment
Primary Outcome Measure Information:
Title
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
Description
From baseline to the end of treatment
Time Frame
Approximately 8 weeks
Secondary Outcome Measure Information:
Title
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
Description
From baseline to the end of treatment
Time Frame
Approximately 8 weeks
Title
Probability of obtaining a negative test, i.e. wild RAS status by the Intplex® test among patients determined wild RAS by the tissue test
Description
From baseline to the end of treatment
Time Frame
Approximately 8 weeks
Title
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
Description
From baseline to the end of treatment
Time Frame
Approximately 8 weeks
Title
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
Description
From baseline to the end of treatment
Time Frame
Approximately 8 weeks
Title
Proportion of patients with a BRAF mutation under anti-EGFR therapy
Description
From baseline to the end of treatment
Time Frame
Approximately 8 weeks
Title
Progression-free survival
Description
From baseline to the database cutoff
Time Frame
Approximately 36 months
Title
Global survival
Description
From baseline to the database cutoff
Time Frame
Approximately 36 months
Title
Evaluation of the following criterion: total concentration of circulating DNA
Description
From baseline to the end of treatment
Time Frame
Approximately 8 weeks
Title
Evaluation of the following criterion: integrity index
Description
From baseline to the end of treatment
Time Frame
Approximately 8 weeks
Title
Evaluation of the following criterion: concentration of mutated alleles
Description
From baseline to the end of treatment
Time Frame
Approximately 8 weeks
Title
Evaluation of the following criterion: frequency of mutated alleles
Description
From baseline to the end of treatment
Time Frame
Approximately 8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Thibault MAZARD, Dr
Phone
0467613000
Ext
+33
Email
thibault.mazard@icm.unicancer.fr
Facility Information:
Facility Name
ICM Val d'Aurelle
City
Montpellier
ZIP/Postal Code
34298
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BLEUSE Jean-pierre
Phone
00467613102
Email
jean-pierre.bleuse@icm.unicancer.fr
Facility Name
Institut du Cancer de Montpellier - Val d'Aurelle
City
Montpellier
ZIP/Postal Code
34298
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marc YCHOU, MD, PhD
Phone
+33467613102
Email
marc.ychou@icm.unicancer.fr

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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