Colorectal Cancer Metastatic

NCT01670721 | Completed Phase 3 Results

• 3 other identifiers: AFLIBL062662012-000048-89U1111-1128-9325
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer Metastatic

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Adverse Events (AEs)

  Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period. On-treatment period was defined as the time from the first dose of treatment to 30 days after the last dose of treatment (either Aflibercept or FOLFIRI). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.

  Baseline upto 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure:723 days)

Secondary Outcomes (3)

• Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment for Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)

  Pre-dose at Baseline, Day 1 of every odd cycle; and at end of treatment (30 days after last study treatment) (maximum exposure: 99 weeks)

• Change From Baseline in HRQL European-Quality of Life-5 Dimension Instrument-3 Levels (EQ-5D-3L) Index Score

  Pre-dose at Baseline, Day 1 of every odd cycle; and at end of treatment (30 days after last study treatment) (maximum exposure: 99 weeks)

• Change From Baseline in HRQL EQ-5D-3L VAS Score

  Pre-dose at Baseline, Day 1 of every odd cycle; and at end of treatment (30 days after last study treatment) (maximum exposure: 99 weeks)

Study Arms (1)

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

EXPERIMENTAL

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.

Drug: AFLIBERCEPT; Drug: Irinotecan; Drug: Fluorouracil; Drug: Leucovorin

Interventions

AFLIBERCEPT DRUG

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

Also known as: AVE0005

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

Irinotecan DRUG

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

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

Fluorouracil DRUG

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

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

Leucovorin DRUG

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

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

Administrative office

Paris, France

Location

MeSH Terms

Interventions

aflibercept; Irinotecan; Fluorouracil; Leucovorin

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2012
• First Posted: August 22, 2012
• Study Start: August 1, 2012
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: November 28, 2016
• Results First Posted: November 28, 2016

Record last verified: 2016-10

Locations

FR (1)