A Prospective Observational Cohort Study Evaluating Resection Rate in Patients With Metastatic Colorectal Cancer Treated With Aflibercept in Combination With FOLFIRI - Observatoire résection

Primary Objective:

-Evaluate the resection rate (R0/R1) in current practice for aflibercept in combination with irinotecan plus 5-fluorouracil (FOLFIRI) in patients treated for metastatic colorectal cancer (mCRC) after failure of an oxaliplatin-containing regimen

Secondary Objectives:

• Evaluate overall survival, progression-free survival and relapse-free survival.
• Evaluate conversion rates (initially unresectable disease which became resectable after chemotherapy, with R0/R1 resection).
• Evaluate histological and radiological response rates.
• Evaluate rate of postoperative complications.
• Evaluate safety.

Study Overview

• Status: Completed
• Conditions: Metastatic Colorectal Cancer; Colorectal Neoplasms
• Intervention / Treatment: Drug: Fluorouracil; Drug: Aflibercept; Drug: Irinotecan

Detailed Description

The estimated inclusion period is 45 months. Patient follow-up is 24 months and the total study duration is 69 months. Last patient status (alive or dead) collected before database lock.

• Study Type: Observational
• Enrollment (Estimated): 140

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The source population for this study will be patients treated with aflibercept in combination with FOLFIRI for metastatic ColoRectal Cancer (mCRC) after failure of an oxaliplatin-containing regimen (including patients pretreated with bevacizumab or anti-estimated glomerular filtration rate (anti-EGFR) and patients treated with oxaliplatin in the adjuvant setting but excluding these already participating in a clinical trial) recruited from particpating sites in France. The study will aim to enroll approximately 140 adult patients treated with aflibercept in combination with FOLFIRI for metastatic colorectal cancer after failure of an oxaliplatin-containing regimen from up to 30 sites.

Description

Inclusion Criteria:

• All patients treated with aflibercept in combination with FOLFIRI for mCRC after failure of an oxaliplatin-containing regimen (including patients pretreated with bevacizumab or anti-EGFR and patients treated with oxaliplatin in the adjuvant setting).
• Exclusively or predominantly hepatic metastases (≤ 5 pulmonary nodules < 2 cm).
• Age > 18 years.
• Signed consent for collection of personal and medical data.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

Exclusion Criteria:

• Concomitant participation in a clinical trial.
• Patient receiving concomitant anti-VEGF agents and/or receiving aflibercept as part of a clinical trial or in a compassionate use program.
• Patient receiving aflibercept in combination with chemotherapy other than FOLFIRI.
• Patient with contra-indication to surgery.

The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Cohort 1; Patients with metastatic colorectal cancer and liver metastases treated with FOLFIRI plus aflibercept after failure of an oxaliplatin-based regimen

Drug: Fluorouracil; Pharmaceutical Form: solution for injection Route of Administration: intravenous (IV), intravenous or intra-arterial infusion; Drug: Aflibercept; Pharmaceutical Form: concentrate solution for infusion Route of Administration: IV infusion; Other Names: ZALTRAP®; Drug: Irinotecan; Pharmaceutical Form: solution for injection Route of Administration: IV infusion; Other Names: CAMPTOSAR®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of resection rate (R0/R1)	R0 /R1 resection rate after aflibercept + FOLFIRI (resection with histological assessment of margin status)	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Defined starting from the date of the first aflibercept administration.	Up to 69 months
Progression-free surivival	Defined as the time from the date of the first aflibercept administration to the date of the first event (progression, relapse or death). (Relapse in case of complete response due to chemotherapy or surgery)	Up to 69 months
Relapse-free surivial	Defined as the time from the date of the first aflibercept administration to the date of the first event (progression, relapse or death). (Relapse in case of complete response due to chemotherapy or surgery)	Up to 69 months
Objective Response	Assessed according to RECIST and CHUN (radiological assessment) criteria in the exploratory analysis.	Up to 69 months
Conversion rate	Initially unresectable disease which became resectable after aflibercept + FOLFIRI, with R0/R1 resection).	Up to 69 months
Histological response of resected patients via Tumor Regression Grade (TRG)	Histological response of resected patients via TRG	Up to 69 months
Histological response of resected patients via Modified Tumor Regression Grade (mTRG)	Histological response of resected patients via mTRG,	Up to 69 months
Histoligical response of resected patients via Blazer assessment		Up to 69 months
Histological response of resected patients via modified Blazer assessment		Up to 69 months
Histological response of resected patients via Sebagh assessment		Up to 69 months
Radiological response for all patients using RECIST 1.1 criteria		Up to 69 months
Rate of 90-day postoperative complications using DINDO-CLAVIEN classification		Up to 69 months
Safety (serious and non-serious adverse events occurring during treatment	Number of patients with serious and non-serious adverse events occurring during treatment	Up to 69 months

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2016
• Primary Completion (Actual): May 27, 2022
• Study Completion (Actual): May 27, 2022

Study Registration Dates

• First Submitted: December 17, 2021
• First Submitted That Met QC Criteria: December 17, 2021
• First Posted (Actual): January 5, 2022

Study Record Updates

• Last Update Posted (Actual): January 22, 2024
• Last Update Submitted That Met QC Criteria: January 19, 2024
• Last Verified: January 1, 2024

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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Topoisomerase I Inhibitors; Fluorouracil; Irinotecan; Aflibercept
• Other Study ID Numbers: OBS15624; AFLIBL07747 (Other Identifier: Sanofi)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No