Colorectal Cancer Metastatic
Condition: Colorectal Cancer Metastatic
MeSH terms: Colorectal Neoplasms
Intervention: AFLIBERCEPT; Irinotecan; Fluorouracil; Leucovorin
Intervention description: Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous; Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous; 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: Leucovorin; Fluorouracil; Irinotecan; Aflibercept
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 175.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      To evaluate the safety of aflibercept in participants with mCRC treated with
      irinotecan/5-Fluorouracil (5-FU) combination (FOLFIRI) after failure of an oxaliplatin-based
      regimen (participants similar to those evaluated in the VELOUR trial [EFC10262, NCT00561470])
      according to side effects prevention and management guidelines.

      Secondary Objective:

      To document the Health-Related Quality of Life (HRQL) of aflibercept in this participant
      population.
    

Eligibility criteria:

        Inclusion criteria:

          -  Histologically or cytologically proven adenocarcinoma of the colon or rectum.

          -  Metastatic disease.

          -  Age ≥18 years.

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.

          -  One and only one prior chemotherapeutic regimen for metastatic disease. This prior
             chemotherapy must be an oxaliplatin containing regimen. Participants must progressed
             during or following the last administration of the oxaliplatin based chemotherapy.
             Participants relapsing within 6 months of completion of oxaliplatin adjuvant
             chemotherapy were also eligible.

          -  Participants must be affiliated to a Social Security System.

        Exclusion criteria:

        Related to Methodology

          -  Prior therapy with irinotecan; Absolute neutrophil counts (ANC) <1.5 x 109/L; Platelet
             count <100 x 109/L; Hemoglobin <9.0 g/dL; Total bilirubin >1.5 x upper limit of normal
             (ULN); Transaminases >3 x ULN (unless liver metastasis are present, 5 x ULN in that
             case); Alkaline phosphatase >3 x ULN (unless liver metastasis are present, 5 x ULN in
             that case).

          -  Less than 4 weeks elapsed from prior radiotherapy or prior chemotherapy or major
             surgery to the time of inclusion or until the surgical wound was fully healed
             whichever came later (48 hours in case of minor surgical procedure or until wound full
             healing observed).

          -  Treatment with any investigational drug within 30 days prior to inclusion.

          -  AEs (with exception of alopecia, peripheral sensory neuropathy and those listed in
             specific exclusion criteria) from any prior anti cancer therapy of grade >1 National
             Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v.4.0 at
             the time of inclusion.

          -  History of brain metastases, uncontrolled spinal cord compression, or carcinomatous
             meningitis or new evidence of brain or leptomeningeal disease.

          -  Other prior malignancy. Basal cell or squamous cell skin cancer, carcinoma in situ of
             the cervix or any other cancer from which the participant had been disease free for >5
             years were allowed.

          -  Any of the following within 6 months prior to inclusion: myocardial infarction,
             severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York
             Heart Association (NYHA) class III or IV congestive heart failure, stroke or transient
             ischemic attack.

          -  Any of the following within 3 months prior to inclusion: Grade 3-4 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 inclusion.

          -  Known acquired immunodeficiency syndrome (AIDS)-related illnesses or known human
             deficiency virus (HIV) disease requiring antiretroviral treatment.

          -  Any severe acute or chronic medical condition, which could impair the ability of the
             participant to participate to the study or to interfere with interpretation of study
             results.

          -  Pregnant or breast-feeding women. Positive pregnancy test for women of reproductive
             potential.

          -  Participants with reproductive potential (female and male) who did not agree to use a
             method of contraception during the study treatment period and for at least 6 months
             following completion of study treatment. The definition of effective method was left
             to the investigator's judgment.

        Related to Aflibercept:

          -  Urine protein-creatinine ratio (UPCR) >1 on morning spot urinalysis or proteinuria >
             500 mg/24-h.

          -  Serum creatinine >1.5 x ULN . If creatinine 1.0-1.5 x ULN, creatinine clearance,
             calculated according to Cockroft-Gault formula, <60 ml/min will exclude the
             participant.

          -  Uncontrolled hypertension (blood pressure >140/90 mmHg or systolic blood pressure >160
             mmHg when diastolic blood pressure <90 mmHg, on at least 2 repeated determinations on
             separate days, or upon clinical judgement within 3 months prior to study inclusion.

          -  Participants on anticoagulant therapy with unstable dose of warfarin and/or having an
             out-of-therapeutic range international normalized ratio (INR) (>3) within the 4 weeks
             prior to inclusion.

          -  Evidence of clinically significant bleeding diathesis or underlying coagulopathy (e.g.
             INR >1.5 without vitamine K antagonist therapy), non-healing wound.

        Related to FOLFIRI

          -  Known dihydropyrimidine dehydrogenase deficiency.

          -  Predisposing colonic or small bowel disorders 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 anticonvulsivant agents that are 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.