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

Colorectal Cancer Metastatic Clinical Trial

— AMOR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01955629
• Other study ID #: AFLIBC06561
• Secondary ID: 2013-000858-22U1
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 13, 2013
• Last updated: April 21, 2015
• Start date: December 2013
• Est. completion date: March 2015

Study information

• Verified date: April 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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 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 survival, overall survival, response to treatment, the overall safety (during induction and maintenance therapy) and the assessment of aflibercept pharmacodynamics and biomarkers parameters.

Description:

The duration of the study for each patient includes a period for screening of up to 3 weeks, study drug administrations every 3 weeks up to disease progression, unacceptable toxicity or patient'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 patient will be followed-up until death, patient'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".

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

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 patient 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.

• 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.

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer Metastatic
• Colorectal Neoplasms

Intervention

Drug:
• AFLIBERCEPT AVE0005
Pharmaceutical form:Concentrate for solution for infusion Route of administration: intravenous
• OXALIPLATIN
Pharmaceutical form:Concentrate for solution for infusion Route of administration: intravenous
• CAPECITABINE
Pharmaceutical form:Tablets Route of administration: oral

Locations

Country	Name	City	State
Italy	Investigational Site Number 380-001	Genova
Italy	Investigational Site Number 380-002	Milano

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Study Part 1: treatment related Dose Limiting Toxicity(ies) (DLTs) observed at first cycle		At 3 weeks (completion of first cycle) for patients included in dose-escalation study Part 1	Yes
Primary	Study Part 2: proportion of patients alive without progression at 6 months after the start of the maintenance therapy		6 months after the start of the maintenance therapy	No
Secondary	Study Part 1: number of patients reporting adverse events or laboratory abnormalities per each dose level tested		At each cycle, at 30 days after the last treatment, up to an estimation of 34 weeks	Yes
Secondary	Study Part 1: Tumor response category: Complete Response (CR), Partial Response (PR), No Change (NC) or Progressive Disease (PD)		Every 9 weeks from treatment start up to the first documentation of disease progression	No
Secondary	Study Part 2: Progression free survival		Study period, approximately 2.5 years	No
Secondary	Study Part 2: Overall survival		Study period, approximately 2.5 years	No
Secondary	Study Part 2: Proportion of patients reaching a total metastases resection (if applicable)		Up to 12 months after the end of study enrollment	No
Secondary	Study Part 2: Proportion of patients with complete or partial response as defined in RECIST 1.1 criteria		Up to 12 months after the end of study enrollment	No
Secondary	Study Part 2: Number of patients reporting adverse events or laboratory abnormalities as per NCI-CTCAE 4.03 criteria		Every cycle up to 30 days after the last treatment administration, study period	Yes
Secondary	Study Part 2: Aflibercept pharmacodynamic parameters evaluation		Up to an average of 34 weeks	No
Secondary	Study Part 2: Aflibercept biomarkers evaluation		Up to an average of 34 weeks	No