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

• Status: Completed
• Trial end date: 2012-03-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of this study is to investigate the safety and tolerability of the anti-vascular endothelial growth factor receptor-2 (anti-VEGFR-2) monoclonal antibody Ramucirumab (IMC-1121B) in combination with irinotecan, levofolinate, and 5-fluorouracil (FOLFIRI) in Japanese participants with advanced colorectal carcinoma (CRC).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Eli Lilly and Company
• Treatments: Antibodies, Monoclonal; Camptothecin; Fluorouracil; Irinotecan; Leucovorin; Levoleucovorin; Ramucirumab

Criteria

Inclusion Criteria:

• Participant is Japanese

• Has an Eastern Cooperative Oncology Group (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 received no more than 2 prior systemic chemotherapy regimens in any setting (only 1 prior regimen for metastatic disease is permitted)

• 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, or discontinued part or all of first-line therapy due to toxicity and experienced disease progression within 6 months after the last dose of first-line therapy. Participants must have received a minimum of 2 doses of bevacizumab as part of a first-line regimen containing chemotherapy in order to enroll.

• Has adequate hepatic, renal, hematologic, and coagulation function

• The participant's urinary protein is ≤1+ on dipstick or routine urinalysis. If urine dipstick or routine analysis indicates proteinuria ≥2+, then a 24-hour urine must be collected and must demonstrate <1000 milligrams (mg) of protein in 24 hours to allow participation in 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

• The participant experienced 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

• Has received wide-field (full-dose pelvic) radiotherapy within 28 days prior to study registration

• Has undergone major surgery within 28 days or subcutaneous venous access device placement within 7 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 [Aspirin up to 325 milligrams per day (mg/day) permitted]

• 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 despite standard medical management

• 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 clinically significant chronic diarrhea

• Has a history of inflammatory bowel disease or Crohn's disease requiring medical intervention within 12 months prior to registration date

• The participant has either peptic ulcer disease associated with a bleeding event or known active diverticulitis

• Has an active infection requiring antibiotic, antifungal, or antiviral therapy

• Has known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness

• Has known leptomeningeal or brain metastases or uncontrolled spinal cord compression

• Has a known history of Gilbert's Syndrome, or is known to have any of the following genotypes: uridine diphosphate glucuronosyltransferase 1 family, polypeptide A1 (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