Clinical Trials/NCT01183780

NCT01183780

Completed

Phase 3

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

Eli Lilly and Company1 site in 1 country1,072 target enrollmentDecember 2, 2010

ConditionsColorectal Cancer

InterventionsRamucirumab Irinotecan Folinic Acid 5-Fluorouracil Placebo

DrugsIrinotecan Folinic Acid 5-Fluorouracil

Overview

Phase: Phase 3
Intervention: Ramucirumab
Conditions: Colorectal Cancer
Sponsor: Eli Lilly and Company
Enrollment: 1072
Locations: 1
Primary Endpoint: Overall Survival (OS)
Status: Completed
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to compare overall survival in participants with metastatic colorectal cancer treated with either ramucirumab and FOLFIRI or placebo and FOLFIRI.

Registry

clinicaltrials.gov

Start Date

December 2, 2010

End Date

June 20, 2016

Last Updated

6 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Eli Lilly and Company

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologically or cytologically confirmed colorectal cancer, excluding primary tumors of appendiceal origin (participants are eligible to enroll irrespective of KRAS mutation status)
•Confirmed metastatic colorectal cancer (Stage IV)
•The participant 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 ≤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 ≤6 months after the last dose of first-line therapy. Note that a participant must have received a minimum of 2 doses of bevacizumab as part of a first-line regimen containing chemotherapy; in addition, a participant must have received at least 1 cycle of first-line therapy that included bevacizumab, oxaliplatin and a fluoropyrimidine in the same cycle. Note that a participant must not have received more than 2 different fluoropyrimidines as part of a first-line regimen; disease progression is not an acceptable reason for discontinuing 1 fluoropyrimidine and starting a second fluoropyrimidine
•Receipt of no more than 2 prior systemic chemotherapy regimens in any setting (only 1 prior regimen for metastatic disease is permitted). For participants with rectal cancer, sequential neoadjuvant and adjuvant therapy will count as a single systemic regimen. Note that rechallenge with oxaliplatin is permitted and will be considered part of the first-line regimen for metastatic disease, both initial oxaliplatin treatment and subsequent rechallenge are considered as 1 regimen
•Measurable or nonmeasurable disease based on the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
•Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
•Adequate hematologic, renal and hepatic function
•Adequate coagulation function \[International Normalized Ratio (INR) ≤1.5 and Partial Thromboplastin Time (PTT) or activated PTT (aPTT) ≤1.5 x upper limit of normal (ULN)). Participants on full-dose anticoagulation must be on a stable dose of anticoagulant therapy and if on oral anticoagulation, must have an INR ≤3 and have no clinically significant active bleeding or pathological condition that carries a high risk of bleeding
•Consent to provide a historical colorectal cancer tissue sample for assessment of biomarkers and the tumor tissue sample is available
•Ability to provide signed informed consent

Exclusion Criteria

•Receipt of bevacizumab ≤28 days prior to randomization
•Receipt of any investigational therapy for non-oncology clinical indication ≤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 (currently or in the past)
•Experience of any arterial thrombotic or arterial thromboembolic events, including, but not limited to, myocardial infarction, transient ischemic attack, or cerebrovascular accident, ≤12 months prior to randomization
•Pregnant (confirmed by serum beta human chorionic gonadotropin (ß HCG) test ≤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) ≤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 ≤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 3 proteinuria, a Grade 3-4 bleeding event, or bowel perforation

Arms & Interventions

FOLFIRI + Ramucirumab

Intervention: Ramucirumab

FOLFIRI + Ramucirumab

Intervention: Irinotecan

FOLFIRI + Ramucirumab

Intervention: Folinic Acid

FOLFIRI + Ramucirumab

Intervention: 5-Fluorouracil

FOLFIRI + Placebo

Intervention: Placebo

FOLFIRI + Placebo

Intervention: Irinotecan

FOLFIRI + Placebo

Intervention: Folinic Acid

FOLFIRI + Placebo

Intervention: 5-Fluorouracil

Outcomes

Primary Outcomes

Overall Survival (OS)

Time Frame: Randomization to Date of Death from Any Cause Up to 39.36 Months

OS was defined as the time in months from the date of randomization to the date of death from any cause. For participants not known to have died as of the cut-off date, OS was censored at the last known date alive.

Secondary Outcomes

Progression-free Survival (PFS) Time(Randomization to Measured PD or Date of Death from Any Cause Up to 38.01 Months)
Percentage of Participants Achieving an Objective Response (Objective Response Rate)(Randomization until Disease Progression Up to 38.01 Months)
Change From Baseline in European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 Global Health Status(Baseline Up to 171 Weeks)
Change From Baseline in EuroQol- 5D (EQ-5D)(Baseline and 30-Day Follow-Up (FU) up to 171 Weeks)
Percentage of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies(Cycles 1, 3, 5, and 30-Day FU)
Observed Maximum Concentration (Cmax) and Observed Minimum Concentration (Cmin) of Ramucirumab(Preinfusion and 1 hour postinfusion in Cycles 3, 5, 9, 13, and 17)