Study of Pazopanib and Vorinostat in Patients With Advanced Malignancies

Inclusion Criteria:

1. Patients with advanced cancer, either refractory to standard therapy or for which no effective standard therapy that increases survival for at least 3 months is available.
2. Patients must have measurable or evaluable disease, as defined by RECIST 1.1.
3. Men or women aged \>/= 18 years. However, patients who are 13 years old or older and have more than 45 kg of body weight will be eligible after consultation with their pediatric attending since the doses of these agents are the fixed doses.
4. Women of child-bearing potential and men must agree to use adequate contraception.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
6. Adequate organ functions: Neutrophils \> 1000/uL, Platelets \>/= 75,000/uL, Total bilirubin \</= 2 x upper limit of normal (ULN) (upper limit of normal), ALT \</= 2.5 x ULN or \</= 5 x ULN if liver metastases persist, Serum creatinine \< 2 x ULN
7. Patients with either previous vascular endothelial growth factor (VEGF) inhibition based treatment or previous vorinostat based treatment are eligible. However, patients who received both VEGF and histone deacetylase (HDAC) inhibition simultaneously are ineligible.
8. Specific to the cohorts as designed to enroll patients with TP53 mutations: TP53 mutations are identified by next-generation sequencing in a chemiluminescence immunoassay analyzer (CLIA)-certified laboratory prior to screening.

Exclusion Criteria:

1. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure (NYHA Class III or IV), or unstable angina pectoris.
2. Inadequately controlled hypertension (defined as systolic blood pressure \>or = 140 and/or diastolic blood pressure \> or = 90 mmHg on antihypertensive medications), any prior history of hypertensive crisis or hypertensive encephalopathy, and history of myocardial infarction or unstable angina within 6 months prior to study enrollment.
3. History of stroke or transient ischemic attack within 6 months prior to study enrollment.
4. Major surgical procedure within 28 days prior to study enrollment.
5. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment.
6. History of allergic reactions to the study drugs, their analogs or any component of the products.
7. Any treatment specific for tumor control within 3 weeks of study drugs; or within 2 weeks if cytotoxic agents were given weekly (within 6 weeks for nitrosoureas or mitomycin C), or within 5 half-lives for targeted agents with half lives and pharmacodynamic effects lasting less than 5 days (that includes but is not limited to erlotinib, sorafenib, sunitinib, bortezomib, and other similar agents). Palliative radiation immediately before or during the study is acceptable provided there is evaluable disease that has not been radiated.
8. Urine for proteinuria \>/= 2+ (patients discovered to have \>/= 2+ proteinuria on urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate \</= 1g of protein in 24 hours to be eligible).
9. Patients with clinical bleeding, active gastric or duodenal ulcer.
10. Symptomatic primary tumors or metastasis of brain and/or central nervous system that are uncontrolled with antiepileptics and requiring high doses of steroids.
11. Concurrent use of antiarrythmics or contraindicated medications (including, but not limited to, cisapride, mesoridazine, pimozide, posaconazole, sparfloxacin, thioridazine).