Study of Intravenous Aflibercept in Combination With FOLFIRI in Japanese Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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The primary objective is to determine the dose of aflibercept to be further studied in combination with irinotecan/5-fluorouracil/isovorin (FOLFIRI) in Japanese patients with metastatic colorectal cancer. Secondary objectives of this study are to assess the safety profile of aflibercept, to determine the pharmacokinetics of aflibercept, to make a preliminary assessment of antitumor effects.

Official Title
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A Dose-escalation Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous Aflibercept in Combination With Intravenous Irinotecan/5-fluorouracil/Isovorin (FOLFIRI) Administered Every 2 Weeks in Patients With Metastatic Colorectal Cancer

Conditions
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Colorectal Neoplasms, Neoplasm Metastasis

Intervention / Treatment
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* Drug: AVE0005 (aflibercept)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically or cytologically proven malignant tumor of the colon or rectum which is metastatic and inoperable. Patients must have received at least one prior line of treatment with any standard of care, who have failed the treatment, or who have not been eligible for standard of care for safety reasons. Exclusion Criteria: Treatment with chemotherapy, hormone therapy, radiotherapy, surgery, blood products, or any investigational agent within 28 days. ECOG Performance Status>1 Anticipated need for a major surgical procedure or radiation therapy during the study. Uncontrolled malignant ascites. History of brain metastases, spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease on screening CT or MRI scan. Pregnant or breast-feeding women. Uncontrolled hypertension Patients who have previously been treated with aflibercept History of abdominal fistula, GI perforation, or intra-abdominal abscess within the past 28 days. History of hypersensitivity to any recombinant proteins, irinotecan, fluoropyrimidine or isovorin. Known dihydropyrimidine dehydrogenase deficiency. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AVE0005 (aflibercept)<br> | Drug: AVE0005 (aflibercept)<br>* IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) combination with FOLFIRI |  | During the first 2 cycles (4 weeks) of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| physical examination, laboratory safety tests, adverse events |  | up to 60 days after last treatment | 
| Pharmacokinetics |  | up to 90 days after last treatment | 
| Tumor burden, endogenous free VEGF |  | every 3 cycles | 
| Immunogenicity |  | up to 90 days after last treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oxaliplatin, 5-FU, Folinic Acid