Study of Aflibercept as Maintenance Therapy Following Induction With Aflibercept in Combination With XELOX, as First-Line Treatment for Metastatic Colorectal Cancer Patient

• Status: Terminated
• Trial end date: 2015-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary Objectives:

Study Part 1: To determine the recommended dose for the aflibercept, oxaliplatin and capecitabine (XELOX) combination to be used in the Part 2 of the study.

Study Part 2: To assess the percentage of participants without progression of the disease at 6 months after the start of maintenance therapy with aflibercept single-agent, following the first-line induction therapy with XELOX and aflibercept combination in participants with previously untreated metastatic colorectal cancer.

Secondary Objective:

Study Part 2: Include the evaluation of progression free survival, overall survival, response to treatment, the overall safety (during induction and maintenance therapy) and the assessment of aflibercept pharmacodynamics and biomarkers parameters.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sanofi
• Collaborator: Regeneron Pharmaceuticals
• Treatments: Aflibercept; Capecitabine; Oxaliplatin

Criteria

Inclusion criteria:

• Histologically or cytologically-proven adenocarcinoma of the colon or rectum.

• Metastatic disease not amenable to potentially curative treatment (i.e. unresectable).

• Measurable lesion as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

• No prior systemic anti-cancer treatment for metastatic disease.

• No prior adjuvant treatment after resection of distant metastases.

• No prior treatment with angiogenesis inhibitors.

Exclusion criteria:

• Age <18 years.

• Eastern Cooperative Oncology Group Performance status >/= 2.

• Less than 4 weeks from prior radiotherapy or prior surgery (or until the surgical wound is fully healed).

• Treatment with any other investigational product within the prior 28 days.

• Other prior neoplasm.

• History of brain metastases, active seizure disorder, uncontrolled spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.

• Any of the following within the prior 6 months: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, severe congestive heart failure, stroke or transient ischemic attack.

• Any of the following within the prior 3 months: moderate/severe 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.

• Deep vein thrombosis within the prior 4 weeks.

• Any severe acute or chronic medical condition, which could impair the ability of the participant to participate in the study.

• Inadequate bone marrow, liver and renal function: neutrophils < 1.5x10^9/L, platelets < 100x10^9/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 >3 x ULN (unless liver metastasis are present), serum creatinine > 1.5 x ULN.

• Participants on anticoagulant therapy with warfarin.

• Symptomatic peripheral sensory neuropathy.

• Inability to take oral medications.

• Prior history of chronic enteropathy, inflammatory enteropathy, chronic diarrhea, malabsorption syndrome, unresolved bowel obstruction/sub-obstruction, surgery more extensive than hemicolectomy, extensive small intestine resection with chronic diarrhea.

• Known dihydropyrimidine dehydrogenase deficiency.

• known history of hypersensitivity to aflibercept.

• Any contraindication to administer oxaliplatin or capecitabine as per package insert of each drug.

• Urine protein-creatinine ratio (UPCR) >1 on morning spot urinalysis or proteinuria > 500 mg/24-h.

• Uncontrolled hypertension within the prior 3 months.

• Evidence of clinically significant bleeding predisposition or underlying coagulopathy, non-healing wound.

• Pregnant or breast-feeding women.

• Participants with reproductive potential who do not agree to use an accepted effective method of contraception.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.