Patients with metastatic colorectal cancer (MCRC) treated with irinotecan/5FU combination (FOLFIRI) after failure of an oxaliplatin based regimen. MedDRA version: 13.1 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: aflibercept, VEGF Trap
Product Code: AVE0005
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: aflibercept
CAS Number: 862111-32-8
Current Sponsor code: AVE
Sponsors
sanofi-aventis recherche & développement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Histologically or cytologically proven adenocarcinoma of the colon or rectum. -Metastatic disease that is not amenable to potentially curative treatment (i.e. inoperable). -Measurable or non measurable disease (as per RECIST criteria). -One and only one prior chemotherapeutic regimen for metastatic disease. This prior chemotherapy must be an oxaliplatin containing regimen. Patients must have progressed during or following the last administration of the oxaliplatin based chemotherapy. Patient who relapse within 6 month of completion of oxaliplatin based adjuvant chemotherapy are eligible. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 783 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 443
Exclusion criteria
Exclusion criteria: -Prior therapy with irinotecan. -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 of randomization. -Adverse events (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 [NCI CTCAE] v.3.0) at the time of randomization. -Age 2. -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 patient has been disease free for > 5 years are 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, NYHA class III or IV congestive heart failure, stroke or transient ischemic attack. -Any of the following within 3 months prior to randomization: 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 randomization. -Known acquired immuno deficiency syndrome (AIDS-related illnesses) or known HIV disease requiring antiretroviral treatment. -Any severe acute or chronic medical condition, which could impair the ability of the patient to participate to the study or to interfere with interpretation of study results. -Pregnant or breast-feeding women. Positive pregnancy test (serum or urine ß-HCG) for women of reproductive potential. Female of reproductive potential enrolled in Austria who does not agree to perform monthly pregnancy testing, as per local regulation. -Patient with reproductive potential (female and male) who do not agree to use an accepted effective method of contraception (hormonal or barrier methods, abstinence) during the study treatment period and for at least 6 months following completion of study treatment. The definition of effective method will be left to the investigator’s judgment. -Absence of signed and dated Institutional Review Board (IRB)/Independent Ethical Committee (IEC)-approved patient informed consent form (ICF) prior to enrollment in the study. -Related to aflibercept: -Urine protein-creatinine ratio (UPCR) >1 urinalysis on morning spot urinalysis or proteinuria > 500 mg/24h -Serum creatinine > 1.5 x upper limit of normal (ULN). If creatinine 1.0-1.5 x ULN, creatinine clearance, calculated according to Cockroft-Gault formula, 150/100 mmHg (grade> or equal at 2 according to NCI CTCAE v. 3.0), or systolic blood pressure >180 mmHg when diastolic blood pressure < 90 mmHg, on at least 2 repeated determinations on separate days within 3 months prior to study enrollment. -Patients on anticoagulant therapy with unstable dose of warfarin an
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate improvement in overall survival (OS) with aflibercept by comparison to placebo in patients with colorectal cancer treated with FOLFIRI as second line treatment for metastatic disease.;Secondary Objective: -To compare progression free survival (PFS) in the 2 treatment arms -To evaluate overall response rate (RR) in the 2 treatment arms -To evaluate the safety profile in the 2 treatment arms -To assess the pharmacokinetics of IV aflibercept -To assess immunogenicity of IV aflibercept ;Primary end point(s): - Overall Survival, defined as the time interval from the date of randomization to the date of death due to any cause. ;Timepoint(s) of evaluation of this end point: - The final OS analysis will be conducted when 863 deaths have been observed. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - To compare progression free survival (PFS) in the 2 treatment arms - To evaluate overall response rate (RR) in the 2 treatment arms - To evaulate the safety profile in the 2 treatment arms - To assess the pharmacokinetics of IV aflibercept -To assess immunogenicity of IV aflibercept ;Timepoint(s) of evaluation of this end point: - The final analysis of progression-free survival will be performed at the time of the second interim analysis of OS. It is expected that approximately 845 PFS events have occurred | — |
Countries
Austria, Belgium, Czech Republic, Denmark, Estonia, France, Germany, Greece, Italy, Netherlands, Spain, Sweden, United Kingdom
Outcome results
None listed