Overview

This trial is active, not recruiting.

Condition colorectal cancer
Treatments ramucirumab, irinotecan, placebo, folinic acid, 5-fluorouracil
Phase phase 3
Target VEGF
Sponsor Eli Lilly and Company
Collaborator ImClone LLC
Start date December 2010
End date July 2014
Trial size 1050 participants
Trial identifier NCT01183780, 13856, 2010-021037-32, CP12-0920, CTRI/2011/07/001900, I4T-MC-JVBB

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
ramucirumab LY3009806
8mg/kg administered intravenously every 2 weeks until disease progression, unacceptable toxicity, noncompliance or withdrawal of consent by the patient or investigator decision
irinotecan
180mg/m2 administered intravenously every 2 weeks until disease progression, unacceptable toxicity, noncompliance or withdrawal of consent by the patient or investigator decision
folinic acid leucovorin
400mg/m2 administered intravenously every 2 weeks until disease progression, unacceptable toxicity, noncompliance or withdrawal of consent by the patient or investigator decision
5-fluorouracil
400mg/m2 bolus immediately followed by 2400mg/m2 continuous infusion every 2 weeks until disease progression, unacceptable toxicity, noncompliance or withdrawal of consent by the patient or investigator decision
(Placebo Comparator)
irinotecan
180mg/m2 administered intravenously every 2 weeks until disease progression, unacceptable toxicity, noncompliance or withdrawal of consent by the patient or investigator decision
placebo
Administered intravenously every 2 weeks until disease progression, unacceptable toxicity, noncompliance or withdrawal of consent by the patient or investigator decision
folinic acid leucovorin
400mg/m2 administered intravenously every 2 weeks until disease progression, unacceptable toxicity, noncompliance or withdrawal of consent by the patient or investigator decision
5-fluorouracil
400mg/m2 bolus immediately followed by 2400mg/m2 continuous infusion every 2 weeks until disease progression, unacceptable toxicity, noncompliance or withdrawal of consent by the patient or investigator decision

Primary Outcomes

Measure
Overall Survival
time frame: Randomization to date of death from any cause

Secondary Outcomes

Measure
Progression-free survival time
time frame: Randomization to measured progressive disease per RECIST 1.1 or date of death from any cause
Proportion of patients achieving an objective response (objective response rate)
time frame: Baseline, every 6 weeks through week 36, then every 12 weeks thereafter until disease progression
Change in European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30
time frame: Every 2 cycles through cycle 14, then every 4 cycles
Incidence of anti-ramucirumab antibodies
time frame: Baseline, 30-day follow-up
Cmax and Cmin of ramucirumab
time frame: Baseline, pre- and post-infusions at cycles 3 and 5, and at 30-day follow-up
Change in EuroQol EQ-5D
time frame: Every 2 cycles through cycle 14, then every 4 cycles

Eligibility Criteria

Male or female participants at least 18 years old.

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 one 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 v. 1.1) - Eastern Cooperative Oncology Group (ECOG) performance status 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 hish 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 - 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 - Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or clinical meaningful ascites resulting from cirrhosis; Clinically meaningful ascites is defined as ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis

Additional Information

Official title 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
Trial information was received from ClinicalTrials.gov and was last updated in July 2014.
Information provided to ClinicalTrials.gov by Eli Lilly and Company.