Folfirinox + Cetuximab Chemotherapy, in First Line, With Wild RAS and According to BRAF Status in Metastatic Colorectal Cancer (ESTER)

A Retrospective Study Assessing the Efficacy and Safety of Triplet Chemotherapy (FOLFIRINOX) Fluorouracil + Oxaliplatin + Irinotecan Plus Cetuximab (ERBITUX®) as First Line Treatment in a RAS (Ras Sarcoma Viral Oncogene Homolog) (KRAS, NRAS) Wild-type Metastatic Colorectal Cancer Population According to BRAF (Murine Sarcoma Viral Oncogene Homolog B) Status and Primary Tumor Location

This retrospective study, will evaluate patient outcomes after triplet chemotherapy (FOLFIRINOX) (5 Fluorouracil + oxaliplatin + irinotecan) plus cetuximab 1st line treatment focusing on efficacy and safety in a RAS (KRAS, NRAS (neuroblastoma rat sarcoma viral oncogene homolog) wild-type metastatic colorectal cancer population, and according to BRAF (murine sarcoma viral oncogene homolog B) status and primary tumor location.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Folfirinox + cetuximab

Detailed Description

In Europe, there are 447,000 new cases of colorectal cancer each year. Approximately 25% of patients present with metastases at initial diagnosis and almost 50% of patients with mCRC (metastatic colorectal cancer) will develop metastases

. Chemotherapy represents the backbone of treatment, and survival is linked with the administration of all three active cytotoxic agents (5-fluorouracil/folinate, oxaliplatin, and irinotecan) in the first line treatment of metastatic colorectal disease.

Monoclonal antibodies such as cetuximab in combination with chemotherapy are a first line treatment option in metastatic RAS (rat sarcoma viral oncogene homolog) wild type metastatic colorectal cancer (mCRC).

Phase II trials evaluating triplet chemotherapy plus cetuximab reported interesting results in terms of efficacy (response rate, resectability...), but at the price of an increased rate of toxic effects.

This retrospective study, will evaluate patient outcomes after triplet chemotherapy (FOLFIRINOX) (5 Fluorouracil + oxaliplatin + irinotecan) plus cetuximab 1st line treatment focusing on efficacy and safety in a RAS (KRAS, NRAS (neuroblastoma rat sarcoma viral oncogene homolog) wild-type mCRC (metastatic colorectal cancer) population, and according to BRAF (murine sarcoma viral oncogene homolog B) status and primary tumor location.

• Study Type: Observational
• Enrollment (Actual): 70

Contacts and Locations

Study Locations

• France
  • Hérault
    • Montpellier, Hérault, France, 34298
      • Institut Régional du Cancer de Montpellier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients who received FOLFIRINOX plus cetuximab (Erbitux®) in first line metastatic colorectal cancer, identified in 3 studies and Medical files from ICM in France:

• Medical files from ICM (Montpellier)
• UNICANCER- PRODIGE 14 study
• ERBIRINOX study
• EREBUS study

Description

Inclusion Criteria:

1. Colorectal cancer confirmed as RAS wild by tumor tissue analysis
2. Non resectable and measurable metastatic disease
3. Patients treated with FOLFIRINOX + cetuximab in first line metastatic disease
4. Males or females aged over 18 years.

Exclusion Criteria:

1. Known brain metastases
2. RAS not assessable (e.g., material not available or insufficient)
3. The first administration of cetuximab was more than 30 days after the first administration of FOLFIRINOX
4. History of other malignancy in the last 5 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Patients with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease-free for at least 5 years

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Progression free survival (PFS)	In RAS wt population	Approximately 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	Rates in RAS wt population	9 months
Overall Response Rate	at the end of 1st line treatment evaluated according RECIST ( Response Evaluation Criteria in Solid Tumours)	Maximal 6 months
Overall Survival	Defined as the time from the date of initial first line treatment initiation to the date of documented death from any cause	Approximately 36 months
Duration of response		Approximately 36 months
Assessment of adverse events by using the NCI-CTCAE version 4.0 scale	Maximum grade observed throughout the treatment	Maximal 6 months
Liver metastases resection rate	Resection (R0 / R1 / R2)	Maximal 6 months

Collaborators and Investigators

• Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
• Collaborators: Merck Serono International SA
• Investigators: Principal Investigator: Emmanuelle SAMALIN, MD, Institut Régional du Cancer de Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2017
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: April 11, 2019
• First Submitted That Met QC Criteria: April 11, 2019
• First Posted (Actual): April 16, 2019

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: colorectal cancer; first line; folfirinox + cetuximab
• 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; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab; Folfirinox
• Other Study ID Numbers: ICM-URC2016/31

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