A Study of Irinotecan, Levofolinate, and 5-Fluorouracil (FOLFIRI)Plus Ramucirumab (IMC-1121B)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01286818
First received: January 25, 2011
Last updated: August 19, 2013
Last verified: August 2013
  Purpose

The primary objective of this study is to investigate the safety and tolerability of the anti-VEGFR-2 monoclonal antibody Ramucirumab (IMC-1121B) in combination with FOLFIRI in Japanese subjects with advanced colorectal carcinoma.


Condition Intervention Phase
Colorectal Carcinoma
Biological: Ramucirumab (IMC-1121B)
Drug: Irinotecan
Drug: levofolinate
Drug: 5-FU
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b Study of Irinotecan, Levofolinate, and 5-Fluorouracil (FOLFIRI) Plus Ramucirumab (IMC-1121B) Drug Product in Japanese Subjects 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:
  • Number of participants that experience any Dose-Limiting Toxicities (DLT) during the the DLT assessment period [ Time Frame: Day 1, Cycle 1 through Day 1, Cycle 3 ] [ Designated as safety issue: Yes ]
  • Number of participants with Adverse Events or Serious Adverse Events [ Time Frame: Approximately 9 Months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Serum Anti-IMC-1121B Antibody Assessment (immunogenicity) [ Time Frame: Approximately 9 Months ] [ Designated as safety issue: Yes ]
    Antibody Assessment will be done prior to infusion in Cycles 1, 5 ,7 and at end of study

  • Maximum concentration (Cmax) of Ramucirumab [ Time Frame: Approximately 18 Weeks ] [ Designated as safety issue: No ]
  • Area under the curve (AUC) of Ramucirumab [ Time Frame: Approximately 18 Weeks ] [ Designated as safety issue: No ]
  • Half life (t 1/2) of Ramucirumab [ Time Frame: Approximately 18 Weeks ] [ Designated as safety issue: No ]
  • Clearance (Cl) of Ramucirumab [ Time Frame: Approximately 18 Weeks ] [ Designated as safety issue: No ]
  • Steady State Volume of Distribution (Vss) of Ramucirumab [ Time Frame: Approximately 18 Weeks ] [ Designated as safety issue: No ]
  • Anti-tumor activity of Ramucirumab (IMC-1121B) with FOLFIRI [ Time Frame: Every 8 weeks until Progressive disease ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: February 2011
Study Completion Date: March 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FOLFIRI plus Ramucirumab (IMC-1121B) Biological: Ramucirumab (IMC-1121B)
IV infusions, 8 mg/kg every 2 weeks
Other Name: IMC-1121B
Drug: Irinotecan
IV Infusion, 180 mg/m² every 2 weeks
Drug: levofolinate
IV infusion, 200 mg/m² every 2 weeks
Drug: 5-FU
400 mg/m² bolus followed by a 2400 mg/m² continuous infusion, every 2 weeks

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant is Japanese
  • Has an ECOG performance status of 0 or 1
  • Has histologically or cytologically confirmed CRC
  • Has metastatic disease that is not amenable to potentially curative resection
  • Has measurable or nonmeasurable disease based on the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v 1.1)
  • Has received no more than 2 prior systemic chemotherapy regimens in any setting
  • Has received first-line combination therapy of bevacizumab, oxaliplatin, and a fluoropyrimidine for metastatic disease and has experienced disease progression during first-line therapy, or disease progression within 6 months after the last dose of first-line therapy
  • Has adequate hepatic, renal, hematologic, and coagulation function
  • Eligible participants of reproductive potential agree to use adequate contraceptive methods during the study period and for 12 weeks after the study

Exclusion Criteria:

  • Has received bevacizumab within 28 days prior to study registration
  • Has received chemotherapy within 21 days prior to study registration
  • Has received any previous systemic therapy (other than a combination of bevacizumab, oxaliplatin, and a fluoropyrimidine) for first-line treatment of metastatic CRC
  • Has received wide-field (full-dose pelvic) radiotherapy within 28 days prior to study registration
  • Has received any investigational therapy within 28 days prior to the study registration date
  • Has undergone major surgery within 28 days prior to study registration
  • Has elective or planned surgery to be conducted during the trial.
  • Has a history of deep vein thrombosis or pulmonary embolism within the past 12 months
  • Has experienced any arterial thrombotic event within the past 12 months.
  • Participant is receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin, or similar agents
  • Participant is receiving chronic therapy with nonsteroidal anti-inflammatory agents
  • Has a significant bleeding disorder or has had a significant (Grade 3 or higher) bleeding event within 3 months prior to registration date
  • Has a history of gastrointestinal perforation and/or fistulae within 6 months prior to registration date
  • Has symptomatic congestive heart failure, unstable angina pectoris, or symptomatic or poorly controlled cardiac arrhythmia
  • Has uncontrolled arterial hypertension
  • Has a serious or nonhealing wound, peptic ulcer or bone fracture within 28 days prior to study registration
  • Has an acute/subacute bowel obstruction or history of chronic diarrhea
  • Has a history of inflammatory bowel disease or Crohn's disease requiring medical intervention within 12 months prior to registration date
  • Has had prior organ transplantation
  • Has an active infection requiring antibiotic, antifungal, or antiviral therapy
  • Has HIV or AIDS
  • Participant is pregnant or lactating
  • Has brain metastases or uncontrolled spinal cord compression
  • Has an uncontrolled metabolic disorder
  • Has a known allergy or hypersensitivity to monoclonal antibody treatment or any components used in ramucirumab DP preparation
  • Has a known allergy or hypersensitivity to any of the study medication components or other contraindication to receive the study medications
  • Has a known history of Gilbert's Syndrome is known to have any of the following genotypes: UGT1A1*6/*6; UGT1A1*28/*28 or UGT1A1*6/*28
  • Has previous or concurrent malignancy, except for basal or squamous cell skin cancer and/or in situ carcinoma, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years
  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: NCT01286818

Locations
Japan
ImClone Investigational Site
Chiba, Japan, 277-8577
ImClone Investigational Site
Osaka, Japan, 569-8686
ImClone Investigational Site
Shizuoka, Japan, 411-8777
Sponsors and Collaborators
Eli Lilly and Company
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: NCT01286818     History of Changes
Other Study ID Numbers: 14223, CP12-1029, 14T-IE-JVBY
Study First Received: January 25, 2011
Last Updated: August 19, 2013
Health Authority: Japan: Institutional Review Board

Keywords provided by Eli Lilly and Company:
Colon Cancer
Rectal Cancer

Additional relevant MeSH terms:
Carcinoma
Colorectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Irinotecan
Fluorouracil
Levoleucovorin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on September 29, 2014