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

Lilly

Status and phase

Completed

Phase 1

Conditions

Colorectal Carcinoma

Treatments

Drug: 5-Fluorouracil (5-FU)

Biological: Ramucirumab (IMC-1121B)

Drug: Irinotecan

Drug: levofolinate

Study type

Interventional

Funder types

Industry

Identifiers

NCT01286818

14223

14T-IE-JVBY (Other Identifier)

CP12-1029 (Other Identifier)

Details and patient eligibility

About

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).

Enrollment

6 patients

Sex

All

Ages

20+ years old

Volunteers

No Healthy Volunteers

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