A Trial of Oral 5-azacitidine in Combination With Romidepsin in Advanced Solid Tumors, With an Expansion Cohort in Virally Mediated Cancers and Liposarcoma

Inclusion Criteria:

* Understand and voluntarily sign informed consent form (ICF).
* Age ≥ 18 years at time of signing ICF.
* Adhere to study visit schedule and other protocol requirements.
* Histologically or cytologically confirmed metastatic or unresectable solid tumor (phase I dose escalation), OR HPV+ nasopharyngeal cancer, HPV+ cervical cancer or liposarcoma (for expansion cohort).
* Failed at least one previous chemotherapy regimen for metastatic disease if standard therapies exist.
* Measurable disease per RECIST 1.1
* Life expectancy ≥ 12 weeks
* No previous cancer therapy ≥ 4 weeks.
* ECOG performance status ≤ 1
* Laboratory test results:

  * Absolute neutrophil count ≥ 1500/mm³
  * Platelet ≥ 100,000/mm³
  * Serum creatinine levels \< 1.5 X ULN OR creatinine clearance \>60 mL/min/1.73 m2 for subjects with creatinine levels \> institutional normal
  * Serum bilirubin ≤ 1.5 times the upper limit of the normal range for the laboratory (ULN).
  * AST (SGOT) and ALT (SGPT) ≤ to 2.5 x ULN
* Disease free of prior malignancies ≥ 5 years (except currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast).
* Women of childbearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment with 5-azacitidine. All men/women of childbearing potential must use acceptable methods of birth control throughout the study.

Exclusion Criteria:

* Serious medical conditions, laboratory abnormality, or psychiatric illness that would prevent the subject from signing ICF.
* Pregnant or breastfeeding women. (Lactating women must agree not to breast feed while taking 5-azacitidine).
* Conditions, including laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret study data.
* Chemotherapy, radiotherapy, or experimental drug or therapy ≤ 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to enrollment or adverse events \< grade 1 due to agents administered \>4 weeks earlier except for stable grade 2 neuropathy.
* No other concomitant investigational agents.
* Known or suspected hypersensitivity to 5-azacitidine, romidepsin, mannitol or other agents used in this study.
* Uncontrolled brain metastases.
* Known positive for HIV, infectious hepatitis, type B or C.
* Uncontrolled intercurrent illness
* Known GI disorders precluding oral administration of 5-azacitidine.
* Known cardiac abnormalities such as:

  * Congenital long QT syndrome
  * QTc interval ≥ 500 milliseconds;
  * Myocardial infarction ≤6 months of C1D1. Subjects with a history of myocardial infarction between 6-12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate;
  * Other significant ECG abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min);
  * Symptomatic coronary artery disease (CAD), e.g., angina. In any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;
  * Screening ECG showing evidence of cardiac ischemia (ST depression, depression of ≥2 mm, measured from isoelectric line to the ST segment). If in any doubt, patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;
  * Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II to IV definitions and/or ejection fraction \<40% by MUGA scan or \<50% by echocardiogram and/or MRI;
  * Known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD);
  * Hypertrophic cardiomegaly or restrictive cardiomyopathy;
  * Uncontrolled hypertension, i.e., blood pressure (BP) of ≥160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria; or
  * Cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)
* Patients taking drugs leading to significant QT prolongation
* Concomitant use of CYP3A4 inhibitors