A Study to Evaluate the Potential of Concomitant Ramucirumab to Affect the Pharmacokinetics of Paclitaxel in Patients With Advanced Malignant Solid Tumors

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 [x
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 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 patients 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 LVEF (left ventricular ejection fraction) not within institutional
limits of normal on a 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 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 patient'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), patient 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 patient 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