Colorectal Cancer Metastatic

NCT ID: NCT01670721

Last Updated: 2016-11-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 175 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2015-06-30

Brief Summary

Primary Objective:

To evaluate the safety of aflibercept in participants with mCRC treated with irinotecan/5-Fluorouracil (5-FU) combination (FOLFIRI) after failure of an oxaliplatin-based regimen (participants similar to those evaluated in the VELOUR trial [EFC10262, NCT00561470]) according to side effects prevention and management guidelines.

Secondary Objective:

To document the Health-Related Quality of Life (HRQL) of aflibercept in this participant population.

Detailed Description

Each participant was treated until disease progression (DP), unacceptable toxicity, death, Investigator's decision or participant's refusal for further treatment (whichever come first). Participants were followed-up during treatment and for at least 30 days after its last study treatment (either Aflibercept or FOLFIRI) administration, up to a maximum of 6 months.

Conditions

Colorectal Cancer Metastatic

Study Design

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

Study Groups

Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)

Aflibercept 4 mg/kg intravenous (IV) infusion over 60 minutes followed by Irinotecan 180 mg/m\^2 IV infusion over 90 minutes and Leucovorin 400 mg/m\^2 IV infusion over 120 minutes at the same time followed by 5-FU 400 mg/m\^2 IV bolus over 2-4 minutes followed by 5-FU 2400 mg/m\^2 continuous IV infusion over 46 hours on Day 1 of each cycle (1 Cycle = 2 weeks), until DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.

Group Type: EXPERIMENTAL

AFLIBERCEPT

Intervention Type: DRUG

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

Irinotecan

Intervention Type: DRUG

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

Fluorouracil

Intervention Type: DRUG

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

Leucovorin

Intervention Type: DRUG

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

Interventions

AFLIBERCEPT

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

Intervention Type: DRUG

Irinotecan

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

Intervention Type: DRUG

Fluorouracil

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

Intervention Type: DRUG

Leucovorin

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

Intervention Type: DRUG

Other Intervention Names

AVE0005

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically proven adenocarcinoma of the colon or rectum.
• Metastatic disease.
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
• One and only one prior chemotherapeutic regimen for metastatic disease. This prior chemotherapy must be an oxaliplatin containing regimen. Participants must progressed during or following the last administration of the oxaliplatin based chemotherapy. Participants relapsing within 6 months of completion of oxaliplatin adjuvant chemotherapy were also eligible.
• Participants must be affiliated to a Social Security System.

Exclusion Criteria

Related to Methodology

• Prior therapy with irinotecan; Absolute neutrophil counts (ANC) <1.5 x 109/L; Platelet count <100 x 109/L; Hemoglobin <9.0 g/dL; Total bilirubin >1.5 x upper limit of normal (ULN); Transaminases >3 x ULN (unless liver metastasis are present, 5 x ULN in that case); Alkaline phosphatase >3 x ULN (unless liver metastasis are present, 5 x ULN in that case).
• Less than 4 weeks elapsed from prior radiotherapy or prior chemotherapy or major surgery to the time of inclusion or until the surgical wound was fully healed whichever came later (48 hours in case of minor surgical procedure or until wound full healing observed).
• Treatment with any investigational drug within 30 days prior to inclusion.
• History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease.
• Other prior malignancy. Basal cell or squamous cell skin cancer, carcinoma in situ of the cervix or any other cancer from which the participant had been disease free for >5 years were allowed.
• Any of the following within 6 months prior to inclusion: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class III or IV congestive heart failure, stroke or transient ischemic attack.
• Any of the following within 3 months prior to inclusion: Grade 3-4 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.
• Occurrence of deep vein thrombosis within 4 weeks, prior to inclusion.
• Known acquired immunodeficiency syndrome (AIDS)-related illnesses or known human deficiency virus (HIV) disease requiring antiretroviral treatment.
• Any severe acute or chronic medical condition, which could impair the ability of the participant to participate to the study or to interfere with interpretation of study results.
• Pregnant or breast-feeding women. Positive pregnancy test for women of reproductive potential.
• Participants with reproductive potential (female and male) who did not agree to use a method of contraception during the study treatment period and for at least 6 months following completion of study treatment. The definition of effective method was left to the investigator's judgment.

Related to Aflibercept:

• Urine protein-creatinine ratio (UPCR) >1 on morning spot urinalysis or proteinuria > 500 mg/24-h.
• Serum creatinine >1.5 x ULN . If creatinine 1.0-1.5 x ULN, creatinine clearance, calculated according to Cockroft-Gault formula, <60 ml/min will exclude the participant.
• Uncontrolled hypertension (blood pressure >140/90 mmHg or systolic blood pressure >160 mmHg when diastolic blood pressure <90 mmHg, on at least 2 repeated determinations on separate days, or upon clinical judgement within 3 months prior to study inclusion.
• Participants on anticoagulant therapy with unstable dose of warfarin and/or having an out-of-therapeutic range international normalized ratio (INR) (>3) within the 4 weeks prior to inclusion.
• Evidence of clinically significant bleeding diathesis or underlying coagulopathy (e.g. INR >1.5 without vitamine K antagonist therapy), non-healing wound.

Related to FOLFIRI

• Known dihydropyrimidine dehydrogenase deficiency.
• Predisposing colonic or small bowel disorders in which the symptoms were uncontrolled as indicated by baseline of >3 loose stools daily.
• Prior history of chronic enteropathy, inflammatory enteropathy, chronic diarrhea, unresolved bowel obstruction/sub-obstruction, more than hemicolectomy, extensive small intestine resection with chronic diarrhea.
• History of anaphylaxis or known intolerance to atropine sulphate or loperamide or appropriate antiemetics to be administered in conjunction with FOLFIRI.
• Treatment with concomitant anticonvulsivant agents that are cytochrome P450 3A4 (CYP3A4) inducers (phenytoin, phenobarbital, carbamazepine), unless discontinued >7 days.
• Participants with known Gilbert's syndrome.

The above information was 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

Administrative office

Paris, , France

Countries

France

Other Identifiers

2012-000048-89

Identifier Type: -

Identifier Source: secondary_id

U1111-1128-9325

Identifier Type: OTHER

Identifier Source: secondary_id

AFLIBL06266

Identifier Type: -

Identifier Source: org_study_id