A Randomized, Double-Blind, Multicenter Phase 3 Study of Irinotecan, Folinic Acid, and 5-Fluorouracil (FOLFIRI) Plus Ramucirumab or Placebo in Patients With Metastatic Colorectal Carcinoma Progressive During or Following First-Line Combination Therapy With Bevacizumab, Oxaliplatin, and a Fluoropyrimidine

Phase 1

Conditions: Metastatic Colorectal Cancer
MedDRA version: 12.1Level: LLTClassification code 10010036Term: Colorectal carcinoma

Registration Number: EUCTR2010-021037-32-FR

Lead Sponsor: Eli Lilly and Company Limited, Indianapolis

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 1050

Inclusion Criteria

- Histologically or cytologically confirmed metastatic colorectal cancer (patients are eligible to enroll irrespective of KRAS mutation status)
- Confirmed metastatic colorectal cancer
- The patient has received first-line combination therapy of bevacizumab, oxaliplatin, and a fluoropyrimidine for metastatic disease and a)Experienced radiographic disease progression during first-line therapy, or b)Experienced radiographic disease progression within 6 months after the last dose of first-line therapy, or c)Discontinued part or all of first-line therapy due to toxicity and experienced radiographic disease progression within 6 months after the last dose of first-line therapy; Note that a patient must have received a minimum of 2 doses of bevacizumab as part of a first-line regimen containing chemotherapy
- Receipt of no more than 2 prior systemic chemotherapy regimens in any setting (only 1 prior regimen for metastatic disease is permitted)
- Measurable or nonmeasurable disease based on the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v. 1.1)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate hematologic, renal, hepatic and coagulation function
- Consent to provide a historical colorectal cancer tissue sample for assessment of biomarkers
- Ability to provide signed informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Receipt of bevacizumab within 28 days prior to randomization
- Receipt of any investigational therapy within 28 days prior to randomization
- Receipt of any previous systemic therapy, other than a combination of bevacizumab, oxaliplatin, and a fluoropyrimidine, for first-line treatment of metastatic colorectal cancer
- Known leptomeningeal disease or brain metastases or uncontrolled spinal cord compression
- Experience of any arterial thrombotic or arterial thromboembolic events, including, but not limited to myocardial infarction, transient ischemic attack, or cerebrovascular accident, within 12 months prior to randomization
- Pregnant (confirmed by serum beta human chorionic gonadotropin [ß HCG] test within 7 days prior to randomization) or lactating
- History of inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) in the 12 months prior to randomization
- Acute or subacute bowel obstruction or history of chronic diarrhea which is considered clinically significant in the opinion of the investigator
- Grade 3 or higher bleeding event within 3 months prior to randomization
- Experience of any of the following during first-line therapy with a bevacizumab-containing regimen: an arterial thrombotic/thromboembolic event, Grade 4 hypertension, Grade 4 proteinuria, a Grade 3-4 bleeding event, or bowel perforation
- Known history or clinical evidence of Gilbert's Syndrome, or is known to have any of the following genotypes: UGT1A1*6/*6, UGT1A1*28/*28, or UGT1A1*6/*28
- Known allergy to any of the study treatment components, including any components used in the preparation of ramucirumab, or other contraindication to receive the study treatments

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to compare overall survival (OS) in patients with metastatic colorectal carcinoma (CRC) when treated with FOLFIRI in combination with placebo versus FOLFIRI in combination with ramucirumab DP.;Secondary Objective: Secondary objectives are to compare FOLFIRI plus placebo treatment with FOLFIRI plus ramucirumab DP treatment for:<br>• progression-free survival (PFS)<br>• objective response rate (ORR)<br>• patient-reported outcome (PRO) measures (using European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 and EuroQol EQ 5D)<br>• safety profile<br>• assessment of the association between biomarkers and clinical outcome<br><br>In addition, secondary objectives include:<br>• assessment of anti-ramucirumab antibodies (immunogenicity)<br>• assessment of serum levels of ramucirumab<br>;Primary end point(s): overall survival

Secondary Outcome Measures