Clinical trial NCT01955629: Study of Aflibercept as Maintenance Therapy Following Induction With Aflibercept in Combination With XELOX, as First-Line Treatment for Metastatic Colorectal Cancer Patient
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer Metastatic
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2013-10-07
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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".

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.

Primary outcomes:
measure: Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Cycle 1 (Up to 3 weeks)
measure: Part 2: Number of Participants With Progression Free Survival (PFS) at 6 Months After the Start of Maintenance Therapy
timeFrame: 6 months after the start of maintenance therapy.
Secondary outcomes:
measure: Part 1: Number of Participants With Tumor Responses (Complete Response [CR], Partial Response [PR], Stable Disease [SD] or Progressive Disease [PD])
timeFrame: Baseline and every 9 weeks up to DP (up to 15 months).
measure: Part 2: Progression Free Survival (PFS)
timeFrame: From the date of enrollment up to the date of DP or death, whichever occurred first (up to 15 months).
measure: Part 2: Overall Survival (OS)
timeFrame: From the date of enrollment up to the date of death (up to 15 months).
measure: Part 2: Overall Rate of Resectability of Metastatic Lesions
timeFrame: 12 months after the last participant enrolled.
measure: Part 2: Number of Participants With CR or PR
timeFrame: Baseline and every 9 weeks up to end of study completion (15 months).
measure: Part 2: Pharmacodynamic Parameters: Modulation of Circulating Analytes
timeFrame: Baseline (within 21 days before registration); Day 1/pre-dose of Cycle 1, 2 and 3 of induction phase and maintenance phase; 30 ± 3 days after the last aflibercept administration.
measure: Part 2: Aflibercept Biomarkers Evaluation
timeFrame: Baseline (within 21 days before registration); Day 1/pre-dose of Cycle 1, 2 and 3 of induction phase and maintenance phase; 30 ± 3 days after the last aflibercept administration.
Other outcomes:
Locations:
city: Genova
country: Italy
facility: Investigational Site Number 380-001
city: Milano
country: Italy
facility: Investigational Site Number 380-002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: