Safety and Quality of Life Study of Aflibercept in Patients With Metastatic Colorectal Cancer Previously Treated With an Oxaliplatin-Based Regimen
Condition: Colorectal Cancer Metastatic
MeSH terms: Colorectal Neoplasms
Intervention: AFLIBERCEPT AVE0005; FOLFIRI
Intervention description: Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous; irinotecan, 5-FU and leucovorin
Intervention MeSH terms: Aflibercept
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 781.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      To provide metastatic colorectal cancer participants with access to aflibercept and to
      document the overall safety in these participants

      Secondary Objective:

      To document the Health-Related Quality of Life of aflibercept in this participants population
    

Eligibility criteria:

        Inclusion criteria :

          -  Histologically or cytologically proven adenocarcinoma of the colon or rectum.

          -  Metastatic disease.

          -  Eastern Cooperative Oncology Group performance status 0-1.

          -  One and only one prior chemotherapeutic regimen for metastatic disease. This prior
             chemotherapy was an oxaliplatin containing regimen. Participants must had progressed
             during or after the oxaliplatin based chemotherapy. Participants relapsed within 6
             months of completion of oxaliplatin adjuvant chemotherapy were eligible.

          -  Signed written informed consent obtained prior to inclusion.

        Exclusion criteria:

          -  Prior therapy with irinotecan.

          -  Inadequate bone marrow, liver and renal function: neutrophils < 1.5x109/L, platelets <
             100x109/L, hemoglobin < 9.0 g/dL, total bilirubin >1.5 x upper normal limit (ULN),
             transaminases >3 x ULN (unless liver metastasis are present), alkaline phosphatase >3
             x ULN (unless liver metastasis are present), serum creatinine > 1.5 x ULN.

          -  Less than 4 weeks from prior radiotherapy, prior chemotherapy, prior major surgery (or
             until the surgical wound were fully healed).

          -  Treatment with any investigational drug within the prior 30 days.

          -  Treatment with concomitant anticonvulsivant agents that were CYP3A4 inducers
             (phenytoin, phenobarbital, carbamazepine), unless discontinued >7 days.

          -  History of brain metastases, uncontrolled spinal cord compression, or carcinomatous
             meningitis or new evidence of brain or leptomeningeal disease.

          -  Prior malignancy (other than colorectal) including prior malignancy from which the
             participants had been disease free for < 5 years (except adequately treated basal or
             squamous cell skin cancer or carcinoma in situ of the cervix).

          -  Any of the following within 6 months prior to study inclusion: myocardial infarction,
             severe/unstable angina pectoris, coronary/peripheral artery bypass graft, severe
             congestive heart failure, stroke or transient ischemic attack.

          -  Any of the following within 3 months prior study inclusion: severe gastrointestinal
             bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive oesophagitis or
             gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary
             embolism or other uncontrolled thromboembolic event.

          -  Occurrence of deep vein thrombosis within 4 weeks, prior to study inclusion.

          -  Known acquired immunodeficiency syndrome (AIDS-related illnesses) or known HIV disease
             requiring antiretroviral treatment.

          -  Known dihydropyrimidine dehydrogenase deficiency.

          -  Predisposing colonic or small bowel disorders in which the symptoms were uncontrolled.

          -  Prior history of chronic enteropathy, inflammatory enteropathy, chronic diarrhea,
             unresolved bowel obstruction/sub-obstruction, more than hemicolectomy, extensive small
             intestine resection with chronic diarrhea.

          -  Known Gilbert's syndrome.

          -  Unresolved or unstable toxicity from any prior anti cancer therapy at the time of
             inclusion.

          -  History of anaphylaxis or known intolerance to atropine sulphate or loperamide or
             appropriate antiemetics to be administered in conjunction with FOLFIRI (irinotecan,
             5-Fluorouracil, leucovorin).

          -  Severe acute or chronic medical condition, which could impair the ability of the
             participants to participate to the study.

          -  Urine protein-creatinine ratio (UPCR) >1 on morning spot urinalysis or proteinuria >
             500 mg/24-h.

          -  Uncontrolled hypertension within 3 months prior to study inclusion.

          -  Participants on anticoagulant therapy with unstable dose of warfarin and/or had an
             out-of-therapeutic range INR within the 4 weeks prior to study inclusion.

          -  Evidence of clinically significant bleeding predisposition or underlying coagulopathy,
             non-healing wound.

          -  Pregnant or breast-feeding women.

          -  Participants with reproductive potential who were not agree to use an accepted
             effective method of contraception.

        The above information wass not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.