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

NCT ID: NCT01955629

Last Updated: 2016-04-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2015-03-31

Brief 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.

Detailed Description

The duration of the study for each participant includes a period for screening of up to 3 weeks, study drug administrations every 3 weeks up to disease progression, unacceptable toxicity or participant's refusal of further study treatment, followed by a minimum of 30-day follow-up after the last study treatment administration.

After study treatment discontinuation each participant will be followed-up until death, participant's refusal or end of study (whichever comes first).

This trial is being conducted in Europe, where the INN designation for the study molecule is "aflibercept" and this term is therefore used throughout the synopsis. In the US, the US proper name is "ziv-aflibercept".

Conditions

Colorectal Cancer Metastatic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Aflibercept + XELOX (Oxaliplatin and Capecitabine)

Aflibercept 6 mg/kg every 3 weeks (q3w) in combination with Oxaliplatin 100 mg/m\^2 q3w and Capecitabine 850 mg/m\^2 twice daily orally (from Day 1 to Day 14 of each cycle), up to 6 cycles as induction therapy, followed by aflibercept 6 mg/kg q3w as maintenance therapy up to disease progression or unacceptable toxicity or participant's refusal of further treatment.

Group Type: EXPERIMENTAL

Aflibercept AVE0005

Intervention Type: DRUG

Pharmaceutical form: Concentrate for solution for infusion; Route of administration: Intravenous

Oxaliplatin

Intervention Type: DRUG

Pharmaceutical form: Concentrate for solution for infusion; Route of administration: Intravenous

Capecitabine

Intervention Type: DRUG

Pharmaceutical form: Tablets; Route of administration: Oral

Interventions

Aflibercept AVE0005

Pharmaceutical form: Concentrate for solution for infusion; Route of administration: Intravenous

Intervention Type: DRUG

Oxaliplatin

Pharmaceutical form: Concentrate for solution for infusion; Route of administration: Intravenous

Intervention Type: DRUG

Capecitabine

Pharmaceutical form: Tablets; Route of administration: Oral

Intervention Type: DRUG

Other Intervention Names

Zaltrap; Eloxatin; SR96669

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 380-001

Genova, , Italy

Investigational Site Number 380-002

Milan, , Italy

Countries

Italy

Other Identifiers

2013-000858-22

Identifier Type: -

Identifier Source: secondary_id

U1111-1143-3015

Identifier Type: OTHER

Identifier Source: secondary_id

AFLIBC06561

Identifier Type: -

Identifier Source: org_study_id