A Study of Irinotecan, Levofolinate, and 5-Fluorouracil (FOLFIRI) Plus Ramucirumab (IMC-1121B)
Condition: Colorectal Carcinoma
MeSH terms: Carcinoma; Colorectal Neoplasms
Intervention: Ramucirumab (IMC-1121B); Irinotecan; levofolinate; 5-Fluorouracil (5-FU)
Intervention description: Ramucirumab (IMC-1121B): Intravenous (IV) infusions, 8 milligrams per kilogram (mg/kg) every 2 weeks; IV Infusion, 180 milligrams per square meter (mg/m²) every 2 weeks; IV infusion, 200 mg/m² every 2 weeks; 400 mg/m² bolus followed by a 2400 mg/m² continuous infusion, every 2 weeks
Intervention MeSH terms: Leucovorin; Fluorouracil; Irinotecan; Ramucirumab; Antibodies, Monoclonal; Levoleucovorin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Colon Cancer; Rectal Cancer

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).
    

Eligibility 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