Safety and Quality of Life Study of Aflibercept in Patients With Metastatic Colorectal Cancer Previously Treated With an Oxaliplatin-Based Regimen

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 priorchemotherapy was an oxaliplatin containing regimen. Participants must had progressedduring or after the oxaliplatin based chemotherapy. Participants relapsed within 6months 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 >3x ULN (unless liver metastasis are present), serum creatinine > 1.5 x ULN.

• Less than 4 weeks from prior radiotherapy, prior chemotherapy, prior major surgery (oruntil 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 carcinomatousmeningitis or new evidence of brain or leptomeningeal disease.

• Prior malignancy (other than colorectal) including prior malignancy from which theparticipants had been disease free for < 5 years (except adequately treated basal orsquamous 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, severecongestive heart failure, stroke or transient ischemic attack.

• Any of the following within 3 months prior study inclusion: severe gastrointestinalbleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive oesophagitis orgastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonaryembolism 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 diseaserequiring 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 smallintestine resection with chronic diarrhea.

• Known Gilbert's syndrome.

• Unresolved or unstable toxicity from any prior anti cancer therapy at the time ofinclusion.

• History of anaphylaxis or known intolerance to atropine sulphate or loperamide orappropriate antiemetics to be administered in conjunction with FOLFIRI (irinotecan, 5-Fluorouracil, leucovorin).

• Severe acute or chronic medical condition, which could impair the ability of theparticipants 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 anout-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 acceptedeffective method of contraception. The above information wass not intended to contain all considerations relevant to aparticipant's potential participation in a clinical trial.