Dose Escalation Study of ARQ 197 in Combination With Gemcitabine in Adult Patients With Advanced Solid Tumors

Inclusion Criteria:

* Written informed consent granted prior to initiation of any study-specific screening procedures, given with the understanding that the patient has the right to withdraw from the study at any time, without prejudice
* 18 year of age or older
* Histologically or cytologically confirmed locally advanced, inoperable or metastatic primary solid tumors
* Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1
* Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN) or ≤ 5 x ULN with metastatic liver disease
* Hemoglobin ≥ 10 g/dl (or ≥ 9 g/dl for expanded cohort)
* Total bilirubin ≤ 1.5 x ULN
* Serum creatinine ≤ 1.5 x ULN
* Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
* Platelets ≥ 100 x 10\^9/L
* Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study drug
* Male and female subjects of child-bearing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after last investigational drug dose received

Exclusion Criteria:

* Other cancer within the last three years, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri or basal or squamous cell carcinoma of the skin
* Previous anti-cancer chemotherapy, radiotherapy, major surgery, immunotherapy or investigational agents within 4 weeks prior to the first day of study defined treatment
* History of cardiac disease: congestive heart failure defined as Class II to IV per New York Heart Association (NYHA) classification; active coronary artery disease (CAD); previously diagnosed bradycardia or other cardiac arrhythmia defined as ≥ Grade 2 according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) (version 3.0), or uncontrolled hypertension; myocardial infarction occurred within 6 months prior to study entry (myocardial infarction occurred \> 6 months prior to study entry is permitted)
* Active clinically serious infections defined as ≥ Grade 2 according to NCI CTCAE, version 3.0
* Substance abuse, medical, psychological or social conditions that may, in the opinion of the Investigator, interfere with the patient's participation in the study or evaluation of the study results
* Any condition that is unstable or which could jeopardize the safety of the patient and his/her protocol compliance
* Known human immunodeficiency virus (HIV) infection
* Pregnancy or breast-feeding
* Inability to swallow oral medications
* Significant gastrointestinal disorder, in the opinion of the Investigator, could interfere with the absorption of ARQ 197 and/or gemcitabine (e.g. significant, uncontrolled inflammatory bowel disease or extensive small bowel resection)
* Central nervous system metastases