HDAC Inhibitor AR-42 and Pazopanib Hydrochloride in Treating Patients with Advanced Soft Tissue or Kidney Cancer

Inclusion Criteria

• Recurrent, unresectable, or metastatic RCC or STS (any histologic type) for which pazopanib is an appropriate therapy
• Measurable or evaluable disease by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Absolute neutrophil count (ANC) >= 1200/mm^3
• Platelets >= 120,000/mm^3
• Hemoglobin >= 9.5 g/dL
• Creatinine =< 1.5 x upper limit of normal (ULN) for the laboratory or calculated or actual creatinine clearance >= 60 mL/min
• Proteinuria =< 2+ (100 mg/dL) using a random urine sample or < 3.0 gm using a 24-hour sample; Note: If urine sample indicates >= 2+ [100 mg/dL]), a 24-hour urine sample must be collected and tested; urine protein in the 24-hour sample must be < 3.0 gm/24 hours
• Total bilirubin =< 1.5 x ULN for the laboratory; Note: Patients with known Gilbert’s syndrome are not eligible for this study
• Aspartate aminotransferase (AST) =< 2.5 x ULN for the laboratory
• Alanine aminotransferase (ALT) =< 2.5 x ULN for the laboratory
• Non-hematologic toxicities from previous cancer therapies resolved to =< grade 1
• International normalized ratio (INR) =< 1.5
• Activated partial thromboplastin time (aPTT) =< 1.5 x ULN for the laboratory
• Left ventricular ejection fraction (LVEF) assessment (eg, echocardiogram, radionuclide ventriculogram scan [MUGA], first-pass technique) performed within 3 months prior to initiation of study treatment indicates an LVEF of >= 50%
• A woman of childbearing potential (WCBP), defined as a woman who is < 60 years of age and has not had a hysterectomy, must have a documented negative serum pregnancy test within 7 days prior to initiating study treatment
• A WCBP and a male patient with a partner who is a WCBP must agree to use a medically accepted method for preventing pregnancy for the duration of study treatment and for 2 months following completion of study treatment
• Ability to understand and willingness to sign the consent form

Exclusion Criteria

• Symptomatic or untreated brain metastasis
• Leptomeningeal metastasis
• Any investigational agent within 4 weeks prior to initiating study treatment
• Previous therapy with pazopanib
• Inability to swallow medication
• Known or suspected malabsorption condition or obstruction
• Contraindication to antiangiogenic agents, including: * Serious non-healing wound, non-healing ulcer, or bone fracture * Major surgical procedure or significant traumatic injury within 4 weeks prior to initiating study treatment; other surgical procedures within 2 weeks prior to initiating study treatment * Pulmonary hemorrhage/bleeding event >= grade 2 within 12 weeks prior to initiating study treatment * Any other hemorrhage/bleeding event >= grade 3 within 12 weeks prior to initiating study treatment
• History of organ allograft including corneal transplant
• Evidence of bleeding diathesis or coagulopathy
• Documented Gilbert’s syndrome
• Resting systolic blood pressure (BP) < 100 mmHg
• Hypertension defined as systolic BP >= 140 mmHg or diastolic BP >= 90 mmHg despite optimal medical management
• Corrected QT (QTc) interval > 450 ms on screening 12-lead electrocardiogram (ECG) * If baseline QTc on screening ECG meets exclusion criteria: ** Check calcium, potassium, and magnesium serum levels ** Correct any identified hypocalcemia, hypokalemia, and/or hypomagnesemia and repeat ECG to confirm exclusion of patient due to prolonged QTc interval * For patients with heart rate (HR) 60-100 beats per minute (bpm), manual read of QTc is not required * For patients with a baseline HR < 60 bpm or > 100 bpm, manual read of the QT interval by a cardiologist is required, with Fridericia correction applied to determine QTc (ie, QTcF)
• Active or clinically significant cardiac disease including any of the following: * Unstable angina (eg, anginal symptoms at rest) or onset of angina within 3 months prior to initiating study treatment * Myocardial infarction within 6 months prior to initiating study treatment * Cardiac arrhythmias currently requiring anti-arrhythmic therapy other than beta blockers
• Any documented history of clinically significant thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident, transient ischemic attack, deep vein thrombosis, or pulmonary embolism necessitating therapeutic anticoagulation within 6 months prior to initiating study treatment; Note: Patients with a tumor-associated thrombus of locally-involved vessels should not be excluded from participating in the study
• Active infection requiring treatment or chronic infection requiring suppressive therapy
• Chronic or active hepatitis B or C infection requiring treatment with antiviral therapy
• Pleural effusion or ascites that causes respiratory compromise (eg, >= grade 2 dyspnea)
• Required ongoing treatment with other drugs thought to potentially have adverse interactions with either of the medications included in the study treatment; if such medications have been used, patients must have discontinued these agents at least 1 week prior to initiating study treatment; examples include: * Strong cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors and/or strong CYP3A4 inducers; * Strong inhibitors of P-glycoprotein (P-gp) and/or breast cancer resistance protein (BCRP); * Simvastatin and other hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (ie, statins) * Drugs that raise gastric potential of hydrogen (pH) including proton pump inhibitors and histamine-2 receptor antagonists (hydrogen [H2]-blockers); Note: Short-acting antacids, in place of proton pump inhibitors (PPIs) and H2-blockers, are permitted * HDAC inhibitors
• Pregnancy or breastfeeding
• Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient’s risk or limit the patient’s adherence with study requirements