PETACC-8 miR-31-3p and miR-31-5p Ancillary Study

Ancillary Study of miR-31-3p and miR-31-5p Expression Levels in Patients Enrolled in the PETACC-8 Study, and of the Predictive Role of miR-31-3p Expression Level on Clinical Outcomes of Patients Treated With Cetuximab

This is a prospective-retrospective study to determine if the expression of the miRNA's miR-31-3p and miR-31-5p are prognostic of patient outcomes or predictive of the benefit from anti-EGFR therapy in stage III Colon Cancer. The present study will utilize FFPE tumor samples collected from patients enrolled in the PETACC-8 study conducted by the Fédération Francophone de Cancérologie Digestive (FFCD). This phase 3 clinical trial prospectively randomized fully resected stage III colon cancer patients to receive adjuvant treatment with either FOLFOX-4 plus cetuximab or FLOFOX-4 alone.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Cetuximab; Drug: FOLFOX

• Study Type: Interventional
• Enrollment (Actual): 1808
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient included in PETACC08 study
• Signed informed consent for translational study
• FFPE tumor sample available for miR-31-3p and miR-31-5p expression testing

Exclusion Criteria:

• Patient who have withdrawn their consent for PETACC08 and/or for PETACC08 translational study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: FOLFOX-4 plus Cetuximab	Drug: Cetuximab; Cetuximab every 2 weeks; Drug: FOLFOX; FOLFOX-4 every 2 weeks
ACTIVE_COMPARATOR: FOLFOX-4	Drug: FOLFOX; FOLFOX-4 every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival (DFS)	Difference in Disease Free Survival (DFS) for RAS/BRAF wild-type patients whose primary tumors have low miR-31-3p expression when treated with cetuximab plus FOLFOX-4 vs. FOLFOX-4 only .	From date of randomization until the date of first documented any signs or symptoms cancer relapse or date of death, whichever came first, assessed up to 7 years
Prognostic and predictive value of miR-31-3p expression on Disease Free Survival (DFS)	If patients with RAS/BRAF wild-type (WT), low miR-31-3p expression tumors treated with cetuximab plus FOLFOX-4 arm have improved DFS vs. patients treated with FOLFOX-4 alone, the predictive and prognostic value of miR-31-3p expression level on cetuximab efficacy relative to DFS in patients with RAS/BRAF WT tumors .	From date of randomization until the date of first documented any signs or symptoms cancer relapse or date of death, whichever came first, assessed up to 7 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Difference in OS for RAS/BRAF wild-type patients whose primary tumors have low miR-31-3p expression when treated with cetuximab plus FOLFOX-4 vs. FOLFOX-4 only.	From date of randomization until date of death from any cause, assessed up to 7 years
Prognostic and predictive value of miR-31-3p expression on OS	If patients with RAS/BRAF wild-type (WT), low miR-31-3p expression tumors treated with cetuximab plus FOLFOX-4 arm have improved OS vs. patients treated with FOLFOX-4 alone, the predictive and prognostic value of miR-31-3p expression level on cetuximab efficacy relative to OS in patients with RAS/BRAF WT tumors .	From date of randomization until date of death from any cause, assessed up to 7 years
Survival after recurrence (SAR)	Difference in Survival after Recurrence (SAR) for RAS/BRAF wild-type patients whose primary tumors have low miR-31-3p expression when treated with cetuximab plus FOLFOX-4 vs. FOLFOX-4 only.	From date of the first documented recurrence to the date of death from any cause, assessed up to 7 years
Prognostic and predictive value of miR-31-3p expression on SAR	If patients with RAS/BRAF wild-type (WT), low miR-31-3p expression tumors treated with cetuximab plus FOLFOX-4 arm have improved SAR vs. patients treated with FOLFOX-4 alone, the predictive and prognostic value of miR-31-3p expression level on cetuximab efficacy relative to SAR in patients with RAS/BRAF WT tumors .	From date of the first documented recurrence to the date of death from any cause, assessed up to 7 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
miR-31-3p cut-off	If pre-established cut-off for miR-31-3p expression does not achieve statistical significance, cut-off value of miR-31-3p expression that discriminates RAS Wild Type and BRAF Wild Type population treated with FOLFOX-4 + cetuximab in terms of DFS, OS and SAR.	From the date of randomization until 7 years, or date of death from any cause.
miR-31-5p cut-off	Cut-off value for miR-31-5p expression which discriminates RAS Wild Type and BRAF Wild Type population treated with FOLFOX-4 + cetuximab in terms of DFS, OS and SAR.	From the date of randomization until 7 years, or date of death from any cause.
Distribution of miR-31-5p expression	Distribution of miR-31-5p expression in the patient population and the correlation of miR-31-5p expression (quantitative) and of miR-31-5p expression level (low/high) with clinically significant co-variates and with the expression of miR-31-3p.	From the date of randomization until 7 years, or date of death from any cause.

Collaborators and Investigators

• Sponsor: IntegraGen SA
• Collaborators: Federation Francophone de Cancerologie Digestive; Exystat
• Investigators: Principal Investigator: Julien Taieb, MD, PhD, Hôpital Européen Georges-Pompidou; Principal Investigator: Pierre Laurent-Puig, MD, PhD, Hôpital Européen Georges-Pompidou

Publications and helpful links

General Publications

• Taieb J, Tabernero J, Mini E, Subtil F, Folprecht G, Van Laethem JL, Thaler J, Bridgewater J, Petersen LN, Blons H, Collette L, Van Cutsem E, Rougier P, Salazar R, Bedenne L, Emile JF, Laurent-Puig P, Lepage C; PETACC-8 Study Investigators. Oxaliplatin, fluorouracil, and leucovorin with or without cetuximab in patients with resected stage III colon cancer (PETACC-8): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Jul;15(8):862-73. doi: 10.1016/S1470-2045(14)70227-X. Epub 2014 Jun 11.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2005
• Primary Completion (ACTUAL): November 1, 2009
• Study Completion (ACTUAL): June 30, 2016

Study Registration Dates

• First Submitted: November 24, 2017
• First Submitted That Met QC Criteria: December 4, 2017
• First Posted (ACTUAL): December 5, 2017

Study Record Updates

• Last Update Posted (ACTUAL): December 5, 2017
• Last Update Submitted That Met QC Criteria: December 4, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• 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
• Other Study ID Numbers: IG2017001

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