A Study of Aflibercept Versus Placebo With FOLFIRI in Patients With Metastatic Colorectal Cancer Previously Treated With an Oxaliplatin Chemotherapy
Condition: Colorectal Cancer Metastatic
MeSH terms: Colorectal Neoplasms
Intervention: Aflibercept; Placebo
Intervention description: Pharmaceutical form: Concentrate for Solution for infusion; Route of administration: Intravenous; Pharmaceutical form: Concentrate for Solution for infusion; Route of administration: Intravenous
Intervention MeSH terms: Aflibercept
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 332.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      To evaluate the improvement in progression-free survival (PFS) of aflibercept versus placebo
      in participants with metastatic colorectal cancer treated with FOLFIRI as second-line
      treatment for metastatic disease.

      Secondary Objectives:

      To compare the overall survival (OS) in the 2 treatment arms. To compare the overall response
      rate (ORR) in the 2 treatment arms. To assess the safety profile of the 2 treatment arms. To
      assess immunogenicity of intravenous (IV) aflibercept in selected centers.
    

Eligibility criteria:

        Inclusion criteria:

          -  Histological or cytological proven adenocarcinoma of the colon or rectum.

          -  Metastatic disease that was not amenable to potentially curative treatment.

          -  One and only one prior chemotherapeutic regimen for metastatic disease. This prior
             chemotherapy must be an oxaliplatin containing regimen. Participants who were relapsed
             within 6 months of completion of oxaliplatin based adjuvant chemotherapy were
             eligible.

        Exclusion criteria:

          -  Prior therapy with irinotecan.

          -  Eastern Cooperative Oncology Group (ECOG) performance status >1.

          -  Less than 28 days elapsed from prior radiotherapy, from prior surgery and prior
             chemotherapy to the time of randomization. Less than 42 days elapsed from prior major
             surgery to the time to randomization.

          -  Adverse events (with exception of alopecia, peripheral sensory neuropathy grade ≤ 2
             and those listed in specific exclusion criteria) from any prior anticancer therapy of
             grade >1 (National Cancer Institute Common terminology Criteria [NCI CTCAE] v.3.0) at
             the time of randomization.

          -  Age <18 years.

          -  History of brain metastases, uncontrolled spinal cord compression, or carcinomatous
             meningitis or new evidence of brain or leptomeningeal disease.

          -  Other prior malignancy. Adequately treated basal cell or squamous cell skin cancer,
             carcinoma in situ of the cervix or any other cancer from which the participants had
             disease free for > 5 years were allowed.

          -  Participation in another clinical trial with an investigational drug and any
             concurrent treatment with any investigational drug within 30 days prior to
             randomization.

          -  Any of the following within 6 months prior to randomization: myocardial infarction,
             severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York
             Heart Association Functional Classification (NYHA) class III or IV congestive heart
             failure, stroke or transient ischemic attack.

          -  Any of the following within 3 months prior to randomization: treatment resistant
             peptic or duodenal ulcer disease, erosive oesophagitis or gastritis, grade 3 or 4
             gastrointestinal bleeding/hemorrhage, gastrointestinal perforation/fistula, abdominal
             abscess, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism,
             or other uncontrolled thromboembolic event.

          -  Participants who had given high dose of aspirin or non steroidal anti-inflammatory
             agents (NSAIDS) or high steroids within 4 weeks prior to randomization. The definition
             of "high dose" was to be based on the investigator's judgment.

          -  Occurrence of deep vein thrombosis within 4 weeks, prior to randomization.

          -  Inadequate organ or bone marrow function.

          -  Pregnant or breast-feeding woman. Positive serum or urine pregnancy test prior to
             randomization. Participants with reproductive (M/F) who were not agree to use accepted
             and effective method of contraception during the study treatment period and for at
             least 6 months following completion of study treatment.

          -  Uncontrolled hypertension.

          -  Urine Protein: creatine ratio (UPCR) >1 on morning spot urinalysis or proteinuria >
             500mg/24 hours.

          -  Participants on anticoagulant therapy with unstable dose of warfarin and/or having an
             out-of-therapeutic range international normalized ratio (INR) (>3) within 4 weeks
             prior to randomization.

          -  Evidence of clinically significant bleeding diathesis or underlying coagulopathy.

          -  Known dihydropyrimidine dehydrogenase deficiency.

          -  Predisposing colonic or small bowel disorder in which the symptoms were uncontrolled
             as indicated by baseline of > 3 loose stools daily.

          -  Prior history of chronic enteropathy, inflammatory enteropathy, chronic diarrhea,
             unresolved bowel obstruction/sub-obstruction, more than hemicolectomy, extensive small
             intestine resection with chronic diarrhea.

          -  History of anaphylaxis or known intolerance to atropine sulphate or loperamide or
             appropriate antiemetics to be administered in conjunction with FOLFIRI.

          -  Treatment with concomitant anticonvulsant agents that were cytochrome P450 3A4
             (CYP3A4) inducers (phenytoin, phenobarbital, carbamazepine), unless discontinued > 7
             days.

          -  Participants with known Gilbert's syndrome.

        The above information was not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.