Aflibercept Versus Placebo in Combination With Irinotecan and 5-FU in the Treatment of Patients With Metastatic Colorectal Cancer After Failure of an Oxaliplatin Based Regimen
Condition: Colorectal Neoplasms; Neoplasm Metastasis
MeSH terms: Neoplasms; Colorectal Neoplasms; Neoplasm Metastasis
Intervention: Placebo; Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®); FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin); FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)
Intervention description: 4 mg/kg of sterile aqueous buffered vehicle (pH 6.0) was administered intra venously (IV) over 1 hour on Day 1, every 2 weeks; 4 mg/kg of Aflibercept was administered IV over 1 hour on Day 1, every 2 weeks.; The FOLFIRI regimen was initiated immediately after Placebo administration on Day 1
The FOLFIRI regimen included:
180 mg/m² Irinotecan (Campto®, Camptosar®) IV infusion over 90 minutes and dl leucovorin 400 mg/m² (200 mg/m² for the l-isomer form) IV infusion over 2 hours, followed by:
5-FU 400 mg/m² IV bolus given over 2-4 minutes, followed by:
5-FU 2400 mg/m² continuous IV infusion over 46-hours; The FOLFIRI regimen was initiated immediately after Aflibercept administration on Day 1
The FOLFIRI regimen included:
180 mg/m² Irinotecan (Campto®, Camptosar®) IV infusion over 90 minutes and dl leucovorin 400 mg/m² (200 mg/m² for the l-isomer form) IV infusion over 2 hours, followed by:
5-FU 400 mg/m² IV bolus given over 2-4 minutes, followed by:
5-FU 2400 mg/m² continuous IV infusion over 46-hours
Intervention MeSH terms: Leucovorin; Fluorouracil; Irinotecan; Aflibercept; Levoleucovorin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 1226.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: colorectal cancer; metastatic; anti-angiogenic; irinotecan; 5-FU; FOLFIRI

Summary:

      The main objective of the study was to evaluate the effectiveness of aflibercept (versus
      placebo) in increasing the overall survival in participants with metastatic colorectal cancer
      treated with FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) and that have previously
      failed an oxaliplatin based treatment for metastatic disease.

      The secondary objectives were to compare progression-free survival, to evaluate overall
      response rate, to evaluate the safety profile, to assess immunogenicity of intravenous (IV)
      aflibercept, and to assess pharmacokinetics of IV aflibercept in both treatment arms.
    

Eligibility criteria:

        Participants who met the following main selection criteria were included in the study.

        Inclusion Criteria:

          -  Histologically or cytologically proven adenocarcinoma of the colon or rectum

          -  Metastatic disease that is not amenable to potentially curative treatment

          -  One and only one prior line of treatment for metastatic disease. This prior line
             should be an oxaliplatin based chemotherapy (participants who relapse within 6 months
             of completion of oxaliplatin based adjuvant chemotherapy are eligible)

          -  Prior treatment with bevacizumab is permitted.

        Exclusion Criteria:

          -  Prior therapy with irinotecan

          -  Eastern Cooperative Oncology Group performance status >2

        The above information is not intended to contain all considerations relevant to
        participation in a clinical trial.