Colorectal cancer metastatic MedDRA version: 16.0 Level: PT Classification code 10052358 Term: Colorectal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Zaltrap
Product Name: Aflibercept
Product Code: AVE0005
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: AFLIBERCEPT
CAS Number: 862111-32-8
Current Sponsor
Sponsors
Sanofi-Aventis Groupe
Eligibility
Sex/Gender
All
Inclusion 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 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 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 61 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 39
Exclusion criteria
Exclusion criteria: - Age /= 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 patient to participate in the study - Inadequate bone marrow, liver and renal function: neutrophils 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 - Patients 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. - Patients with reproductive potential who do not agree to use an accepted effective method of contraception.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 patients 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 patients with previously untreated metastatic colorectal cancer ;Secondary Objective: Study Part 2: Include the evaluation of progression free survial, overall survival, response to treatment, the overall safety (during induction and maintenance therapy) and the assessment of aflibercept pharmacodynamics and biomarkers parameters.;Primary end point(s): Study Part 1: treatment related Dose Limiting Toxicity(ies) (DLTs) observed at first cycle Study Part 2: proportion of patients alive without progression at 6 months after the start of the maintenance therapy;Timepoint(s) of evaluation of this end point: Study Part 1: at the end of the first cycle of treatment up to the end of dose-escalation study Part 1 Study Part 2: 6 months after the start of the maintenance therapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): a) Study Part 1: number of patients reporting adverse events or laboratory abnormalities per each dose level tested b) Study Part 1: Tumor response category: Complete Response (CR), Partial Response (PR), No Change (NC) or Progressive Disease (PD) c) Study Part 2: Progression free survival d) Study Part 2: Overall survival e) Study Part 2: Proportion of patients reaching a total metastases resection (if applicable) f) Study Part 2: Proportion of patients with complete or partial response as defined in RECIST 1.1 criteria g) Study Part 2: Number of patients reporting adverse events or laboratory abnormalities as per NCI-CTCAE 4.03 criteria h) Study Part 2: Aflibercept pharmacodynamic parameters evaluation i) Study Part 2: Aflibercept biomarkers evaluation;Timepoint(s) of evaluation of this end point: a) Every cycle up to 30 days after the last treatment administration, study period b) Every 9 weeks up to disease progressio c) Study period, approximately 2.5 years d) Study period, approximately 2.5 years e) Up to 12 months after the end of study enrollment f) Up to 12 months after the end of study enrollment g) Every cycle up to 30 days after the last treatment administration, study period h) During the study treatment period i) During the study treatment period | — |
Countries
Italy
Outcome results
None listed