A Study to Assess the Pharmacokinetics of Ramucirumab (IMC-1121B) in Combination With FOLFIRI
Condition: Solid Tumors
Intervention: Ramucirumab (IMC-1121B); Irinotecan; Folinic acid; 5-Fluorouracil
Intervention description: Ramucirumab (IMC-1121B) 8 milligrams per kilogram (mg/kg), administered as an intravenous (IV) infusion on Day 1 of each 2-week cycle (except Cycle 1); 180 milligrams per square meter (mg/m²) administered IV on Day 1 of each cycle; 400 mg/m² administered IV on Day 1 of each cycle; 400 mg/m² bolus over 2 to 4 minutes administered IV on Day 1 of each cycle, followed by 2400 mg/m² administered IV over 46 to 48 hours on Days 1 and 2 of each cycle
Intervention MeSH terms: Leucovorin; Folic Acid; Fluorouracil; Irinotecan; Ramucirumab; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced Malignant Solid Tumors

Summary:

      The purpose of this study is to assess the effect of concomitant ramucirumab (IMC-1121B) on
      the pharmacokinetics of irinotecan and its metabolite SN-38 when coadministered with folinic
      acid and 5-fluorouracil, in participants with advanced malignant solid tumors resistant to
      standard therapy or for which no standard therapy is available.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has histologic or cytologic documentation of a malignant solid tumor

          -  Has an advanced solid tumor that is resistant to standard therapy or for which no
             standard therapy is available

          -  Has resolution to Grade ≤1, per the National Cancer Institute Common Terminology
             Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v. 4.0), of all clinically
             significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal
             therapy

          -  Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

          -  Has adequate hematologic, coagulation, and hepatic function

          -  Has serum creatinine ≤ 1.5 x upper limit of normal (ULN)

          -  Urinary protein is <2+ on dipstick or routine urinalysis (UA) at study entry

          -  Women with childbearing potential must have a negative serum or urine pregnancy test

          -  Eligible participants of reproductive potential (both sexes) agree to use adequate
             method of contraception during the study period and for 12 weeks after the last dose
             of study medication

        Exclusion Criteria:

          -  Has received a therapeutic monoclonal antibody within the last 42 days

          -  Has received cytotoxic chemotherapy within the last 21 days

          -  Has received radiotherapy within the last 14 days

          -  Are currently enrolled in, or discontinued within the last 14 days from, a clinical
             trial involving an investigational product or non-approved use of a drug or device, or
             concurrently enrolled in any other type of medical research judged not to be
             scientifically or medically compatible with this study

          -  Has a history of deep vein thrombosis, pulmonary embolism, or any other significant
             thromboembolism during the last 3 months

          -  Has an uncontrolled illness, including, but not limited to uncontrolled hypertension,
             symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly
             controlled cardiac arrhythmia, psychiatric illness/social situations, or any other
             serious uncontrolled medical disorders

          -  Has experienced any arterial thromboembolic event within the last 6 months

          -  Has known leptomeningeal disease or brain metastases or uncontrolled spinal cord
             compression

          -  Has an ongoing or active infection requiring parenteral antibiotic, antifungal, or
             antiviral therapy

          -  Has known human immunodeficiency virus infection or acquired immunodeficiency
             syndrome-related illness

          -  Has received a prior organ or transplantation

          -  Has undergone major surgery within the last 28 days

          -  Has had a serious nonhealing wound, ulcer, or bone fracture within the last 28 days

          -  Has an elective or planned major surgery to be performed during the course of the
             trial

          -  Has a bowel obstruction, history or presence of inflammatory enteropathy or extensive
             intestinal resection, Crohn's disease, ulcerative colitis, or chronic diarrhea

          -  Has experienced a Grade 3 or higher bleeding event within the last 3 months

          -  Has a known history or clinical evidence of Gilbert's Syndrome, or is known to have
             any of the following genotypes: uridine diphosphate glucuronosyltransferase isoform
             1A1 (UGT1A1)*6/*6, UGT1A1*28/*28, or UGT1A1*6/*28

          -  Has received clinically relevant inhibitors or inducers of cytochrome P (CYP) 450
             CYP3A4/5 or CYP2C9 and/or isoenzymes within the last 3 weeks

          -  Has cirrhosis at a level of Child-Pugh B (or worse), or cirrhosis and a history of
             hepatic encephalopathy, or ascites resulting from cirrhosis and requiring ongoing
             treatment with diuretics and/or paracentesis