A Study of Ramucirumab (IMC-1121B) and Paclitaxel in Participants With Solid Tumors
Condition: Malignant Solid Tumor
MeSH terms: Neoplasms
Intervention: ramucirumab (IMC-1121B); paclitaxel
Intervention description: ramucirumab (IMC-1121B) 8 milligrams/kilogram (mg/kg) intravenous infusion, administered on Day 1and Day 15 of each 4-week cycle, unless otherwise specified.; paclitaxel 80 milligrams/square meter (mg/m²) intravenous infusion, administered on Days 1, 8 and 15 of each 4-week cycle, unless otherwise specified.
Intervention MeSH terms: Paclitaxel; Ramucirumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced Malignant Solid Tumors

Summary:

      The purpose of this study is to investigate whether there are no clinically significant
      pharmacokinetic effects of concomitant ramucirumab (IMC-1121B) on paclitaxel by investigating
      the pharmacokinetics (PK) of each in participants with advanced malignant solid tumors.

      Part A of this study will investigate the potential of concomitant ramucirumab (IMC-1121B) to
      affect the pharmacokinetics of paclitaxel. Part B of this study will investigate the
      pharmacokinetics of ramucirumab (IMC-1121B) as monotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has histologic or cytologic documentation of a malignant solid tumor

          -  Has an advanced solid tumor that is refractory to standard therapy or for which no
             standard therapy is available

          -  Part A only: Has had 0-1 prior taxane-containing treatment regimens (including taxane
             monotherapy), which must have been completed at least 6 months before the first dose
             of study medication (prior bevacizumab is allowed)

          -  Part B only: Prior bevacizumab- and taxane-containing treatment regimens (including
             taxane monotherapy) are allowed, provided these regimens have been completed at least
             6 months before the first dose of study medication

          -  Has resolution to Grade ≤ 1 of all clinically significant toxic effects of prior
             chemotherapy, surgery, radiotherapy, or hormonal therapy with the exception of
             peripheral neuropathy, which must not have exceeded Grade 1, by the National Cancer
             Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v
             4.0)

          -  Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 - 2

          -  Has adequate hematologic function. Blood transfusion is allowed but must be completed
             48 hours before study drug administration

          -  Has adequate hepatic function (bilirubin ≤ 1.5 times the upper limit of normal [ULN],
             aspartate transaminase [AST] and alanine transaminase [ALT] ≤ 1.5 x ULN

          -  Has serum creatinine ≤ 1.5 x ULN. If serum creatinine > 1.5 x ULN, the calculated
             creatinine clearance (CrCl) should be ≥ 40 milliliter/minute (mL/min)

          -  Urinary protein is <2+ on dipstick or routine urinalysis (UA)

          -  Must have adequate coagulation function as defined by an international normalized
             ratio (INR) of ≤ 1.5 and a partial thromboplastin time (PTT) or an activated PTT
             (aPTT) ≤ 1.5 x ULN

          -  Eligible participants of reproductive potential agree to use adequate method of
             contraception during the study period and for 12 weeks after the last dose of study
             medication

        Exclusion Criteria:

          -  Is receiving concomitant therapy with clinically relevant inhibitors or inducers of
             cytochrome P450, CYP2C8, CYP3AY and/or isoenzymes

          -  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 received a monoclonal antibody within 42 days prior to first dose of study
             medication

          -  Has received radiotherapy within 14 days prior to first dose of study medication

          -  Has received cytotoxic chemotherapy within 21 days (6 weeks for nitrosoureas or
             mitomycin C) prior to first dose of study medication

          -  Has a cardiac left ventricular ejection fraction (LVEF) not within institutional
             limits of normal on a multigated acquisition scan (MUGA) or echocardiogram

          -  Is receiving concurrent treatment with another anticancer therapy, including
             chemotherapy, immunotherapy, hormonal therapy, radiation therapy, chemoembolization,
             targeted or other investigational anticancer therapy

          -  Is receiving chronic therapy with nonsteroidal anti-inflammatory agents or other
             antiplatelet agents. Aspirin use at doses up to 325 milligrams/day (mg/day) and
             analgesic agents with no or low bleeding risk are permitted

          -  Has a history of uncontrolled hereditary or acquired bleeding or thromboembolic
             disorders

          -  Has experienced any arterial thromboembolic event, including myocardial infarction
             (MI), unstable angina stroke or transient ischemic attack (TIA), within 6 months prior
             to first dose of study medication

          -  Has a history of deep vein thrombosis, pulmonary embolism, or any other significant
             thromboembolism during the 3 months prior to first dose of study medication

          -  Has experienced a Grade 3 or 4 hemorrhagic event within 3 months prior to first dose
             of study medication

          -  Has experienced peripheral neuropathy ≥ Grade 2 at any time prior to study entry

          -  Has a bowel obstruction, history or presence of inflammatory enteropathy or extensive
             intestinal resection, Crohn's disease, ulcerative colitis, or chronic diarrhea

          -  History of gastrointestinal perforation and / or fistulae within 6 months prior to
             randomization

          -  Has an ongoing or active infection requiring treatment with intravenous antibiotics

          -  Has a serious or nonhealing wound, peptic ulcer, or bone fracture within 28 days prior
             to first dose of study medication

          -  Has uncontrolled hypertension

          -  Has symptomatic congestive heart failure

          -  Has known brain or leptomeningeal disease

          -  Has known positive status for human immunodeficiency virus (HIV) infection or acquired
             immunodeficiency syndrome-related illness

          -  Has known active drug or alcohol abuse that would affect participant's ability to
             comply with study treatment

          -  Has pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring
             active treatment, including the use of oxygen

          -  Has had major surgery within 28 days prior to first dose of study medication or
             subcutaneous venous access device implantation within 7 days prior to first dose of
             study medication

          -  Has an elective or planned major surgery during the course of the trial

          -  If a primary cancer is non-small-cell lung cancer (NSCLC), participant has intratumor
             cavitation, radiologically documented evidence of major blood vessel invasion or
             encasement by cancer, or proximity of cancer to major airways

          -  Has received prior ramucirumab (IMC-1121B) therapy

          -  The participant has:

               -  cirrhosis at a level of Child-Pugh B (or worse)

               -  cirrhosis (any degree) and a history of hepatic encephalopathy or ascites
                  resulting from cirrhosis and requiring ongoing treatment with diuretics and/or
                  paracentesis