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-GR

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
- The patient has received no more than 2 prior systemic chemotherapy regimens in
any setting (only 1 prior regimen for metastatic disease is permitted). For patients
with rectal cancer, sequential neoadjuvant and adjuvant therapy will count as a single
systemic regimen
- 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