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

• ClinicalTrials.gov Identifier: NCT03362684
• Recruitment Status: Completed
• First Posted: December 5, 2017
• Last Update Posted: December 5, 2017
• Sponsor: IntegraGen SA
• Collaborators: Federation Francophone de Cancerologie Digestive; Exystat
• Information provided by (Responsible Party): IntegraGen SA

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Colorectal Cancer	Drug: Cetuximab; Drug: FOLFOX	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1808 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: November 2005
• Actual Primary Completion Date: November 2009
• Actual Study Completion Date: June 30, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Disease Free Survival (DFS) [ Time Frame: 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 ]
   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 .
2. Prognostic and predictive value of miR-31-3p expression on Disease Free Survival (DFS) [ Time Frame: 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 ]
   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 .

Secondary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: From date of randomization until date of death from any cause, assessed up to 7 years ]
   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.
2. Prognostic and predictive value of miR-31-3p expression on OS [ Time Frame: From date of randomization until date of death from any cause, assessed up to 7 years ]
   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 .
3. Survival after recurrence (SAR) [ Time Frame: From date of the first documented recurrence to the date of death from any cause, assessed up to 7 years ]
   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.
4. Prognostic and predictive value of miR-31-3p expression on SAR [ Time Frame: From date of the first documented recurrence to the date of death from any cause, assessed up to 7 years ]
   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 .

Other Outcome Measures:

1. miR-31-3p cut-off [ Time Frame: From the date of randomization until 7 years, or date of death from any cause. ]
   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.
2. miR-31-5p cut-off [ Time Frame: From the date of randomization until 7 years, or date of death from any cause. ]
   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.
3. Distribution of miR-31-5p expression [ Time Frame: From the date of randomization until 7 years, or date of death from any cause. ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 74 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Sponsors and Collaborators

IntegraGen SA

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

More Information

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.

• Responsible Party: IntegraGen SA
• ClinicalTrials.gov Identifier: NCT03362684
• Other Study ID Numbers: IG2017001
• First Posted: December 5, 2017
• Last Update Posted: December 5, 2017
• Last Verified: December 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Cetuximab; Antineoplastic Agents, Immunological; Antineoplastic Agents