A Study in Second Line Metastatic Colorectal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
ImClone LLC
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01183780
First received: August 4, 2010
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Biological: Ramucirumab
Drug: Irinotecan
Biological: Placebo
Drug: Folinic Acid
Drug: 5-Fluorouracil
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: Randomization to date of death from any cause ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival time [ Time Frame: Randomization to measured progressive disease per RECIST 1.1 or date of death from any cause ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Incidence of anti-ramucirumab antibodies [ Time Frame: Baseline, 30-day follow-up ] [ Designated as safety issue: Yes ]
  • Cmax and Cmin of ramucirumab [ Time Frame: Baseline, pre- and post-infusions at cycles 3 and 5, and at 30-day follow-up ] [ Designated as safety issue: No ]
  • Change in EuroQol EQ-5D [ Time Frame: Every 2 cycles through cycle 14, then every 4 cycles ] [ Designated as safety issue: No ]

Estimated Enrollment: 1050
Study Start Date: December 2010
Estimated Study Completion Date: February 2016
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FOLFIRI + Ramucirumab Biological: Ramucirumab
8mg/kg administered intravenously every 2 weeks until disease progression, unacceptable toxicity, noncompliance or withdrawal of consent by the patient or investigator decision
Other Names:
  • LY3009806
  • IMC-1121B
Drug: Irinotecan
180mg/m2 administered intravenously every 2 weeks until disease progression, unacceptable toxicity, noncompliance or withdrawal of consent by the patient or investigator decision
Drug: Folinic Acid
400mg/m2 administered intravenously every 2 weeks until disease progression, unacceptable toxicity, noncompliance or withdrawal of consent by the patient or investigator decision
Other Name: leucovorin
Drug: 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: FOLFIRI + Placebo Drug: Irinotecan
180mg/m2 administered intravenously every 2 weeks until disease progression, unacceptable toxicity, noncompliance or withdrawal of consent by the patient or investigator decision
Biological: Placebo
Administered intravenously every 2 weeks until disease progression, unacceptable toxicity, noncompliance or withdrawal of consent by the patient or investigator decision
Drug: Folinic Acid
400mg/m2 administered intravenously every 2 weeks until disease progression, unacceptable toxicity, noncompliance or withdrawal of consent by the patient or investigator decision
Other Name: leucovorin
Drug: 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01183780

  Show 214 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
ImClone LLC
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01183780     History of Changes
Other Study ID Numbers: 13856, I4T-MC-JVBB, CP12-0920, 2010-021037-32, CTRI/2011/07/001900
Study First Received: August 4, 2010
Last Updated: July 21, 2014
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Federal Office for Safety in Health Care
Belgium: Ministry of Social Affairs, Public Health and the Environment
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
India: Drugs Controller General of India
Italy: The Italian Medicines Agency
Japan: Ministry of Health, Labor and Welfare
Japan: Pharmaceuticals and Medical Devices Agency
Korea: Food and Drug Administration
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Portugal: National Pharmacy and Medicines Institute
Portugal: Ethics Committee for Clinical Research
Romania: National Medicines Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency
Taiwan: Department of Health
United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
second line
metastatic colorectal cancer
FOLFIRI
ramucirumab
CRC
mCRC

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Levoleucovorin
Folic Acid
Fluorouracil
Irinotecan
Antidotes
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Hematinics
Hematologic Agents
Therapeutic Uses
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 30, 2014