Pazopanib and ARQ 197 for Advanced Solid Tumors

• ELIGIBILITY CRITERIA:
• Patients with histologically confirmed (by the Laboratory of Pathology, National Institutes of Health (NIH) solid tumors that have progressed following at least one line of standard therapy or for whom no standard treatment options exist.
• Patients must have measurable or evaluable disease.
• Patients enrolling in the expansion cohorts must have disease amenable to biopsy, and be willing to undergo pre-and post-treatment biopsies.
• Patients must have completed any chemotherapy, radiation therapy, or biologic therapy greater than or equal to 4 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin C). Patients must be greater than or equal to 2 weeks since any prior administration of a study drug in a phase 0 or equivalent study. Patients must have recovered to eligibility levels from prior toxicity or adverse events. Treatment with bisphosphonates is permitted.
• Patients who have had prior treatment with any anti-angiogenic therapy and/or mesenchymal epithelial transition factor (c-MET) inhibitor are eligible in the dose escalation phase unless the antiangiogenic therapy and/or c-MET inhibitor were administered within the 4 weeks prior to entering the study. In the expansion phase, prior c-MET inhibitor is not allowed, and anti-angiogenic therapy is allowed unless it was administered within the 3 months prior to entering the study.
• Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of pazopanib in combination with ARQ 197 (Tivantinib) in patients less than 18 years of age, children are excluded from this study.
• Life expectancy greater than 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Patients must have normal organ and marrow function as defined below:
• Absolute neutrophil count greater than or equal to 1,500/microL
• Platelets greater than or equal to 100,000/microL
• Total bilirubin less than or equal to 1.5 X institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase(SGOT)/alanine transaminase (ALT) serum glutamic pyruvic transaminase(SGPT) less than or equal to 2.5 X institutional ULN
• Creatinine less than or equal to 1.5 mg/dL (133 mcmol/L); OR
• Measured creatinine greater than or equal to 60 mL/minute for patients with clearance creatinine levels greater than 1.5 mg/dL
• Urine protein/creatinine ratio less than 1 OR 24-hour urine protein less than 1 gram
• Subjects who have both bilirubin greater than ULN and AST/ALT greater than ULN are not eligible.
• Subjects in the expansion cohort must have prothrombin time (PT)/ international normalized ratio (INR)/partial thromboplastin time (PTT) less than or equal to 1.2 X institutional ULN, except patients with confirmed positive lupus anticoagulant test.
• Subjects must have blood pressure (BP) no greater than 140 mmHg (systolic) and 90 mmHg (diastolic) for eligibility. Initiation or adjustment of BP medication is permitted prior to study entry provided that the average of three BP readings at a visit prior to enrollment is less than 140/90 mmHg.
• The effects of study drugs on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 2 months after dosing with study drugs ceases. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Women of child-bearing potential must have a negative pregnancy test prior to entry.
• Patients must be able to swallow whole tablets or capsules. Nasogastric or G-tube administration is not allowed.
• Ability to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA