Testing the Addition of an Anti-Cancer Drug, ZEN003694, to the Usual Chemotherapy Treatment (Capecitabine) for Metastatic or Unresectable Cancers

Inclusion Criteria:

• Dose Escalation additional criteria: Patients must have histologically confirmedcancer that is metastatic or unresectable and must have progressed on standardtherapies which would have included fluorouracil (5-FU) or capecitabine

• Dose Escalation additional criteria specifically for colorectal cancer (CRC)patients: Willingness and ability to undergo a pre-treatment biopsy

• Dose Expansion additional criteria: Patients must have histologically confirmed CRCthat is metastatic or unresectable and must have progressed on standard therapieswhich would have included 5-FU or capecitabine

• Dose Expansion additional criteria: Willingness and ability to undergo pre- and on-treatment biopsies

• Patients must have measurable disease

• Age >= 18 years. Because no dosing or adverse event data are currently available onthe use of ZEN003694 (ZEN-3694) in combination with capecitabine in patients < 18years of age, children are excluded from this study

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Karnofsky >= 60%)

• Availability of archival tumor tissue at the time of patient enrollment formolecular profiling studies

• Prior to study dosing, previous systemic therapy must have been completed for atleast five half-lives or 2 weeks, whichever is shorter

• Absolute neutrophil count >= 1,000/mcL

• Platelets >= 100,000/mcL

• Total bilirubin =< 1.5 institutional upper limit of normal (ULN)

• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN

• Glomerular filtration rate (GFR) >= 50 mL/min/1.73 m^2

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviraltherapy with undetectable viral load within 6 months are eligible for this trial

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBVviral load must be undetectable on suppressive therapy, if indicated

• Patients with a history of hepatitis C virus (HCV) infection must have been treatedand cured. For patients with HCV infection who are currently on treatment, they areeligible if they have an undetectable HCV viral load

• Patients with treated brain metastases are eligible if follow-up brain imaging aftercentral nervous system (CNS)-directed therapy shows no evidence of progression

• Patients with a prior or concurrent malignancy whose natural history or treatmentdoes not have the potential to interfere with the safety or efficacy assessment ofthe investigational regimen are eligible for this trial

• Patients should be New York Heart Association Functional Classification of class 2Bor better

• The effects of ZEN003694 (ZEN-3694) and capecitabine on the developing human fetusare unknown. For this reason and because BET inhibitors as well as other therapeuticagents used in this trial are known to be teratogenic, women of child-bearingpotential and men must agree to use adequate contraception (hormonal or barriermethod of birth control; abstinence) prior to study entry and for the duration ofstudy participation. Women of child-bearing potential and men treated or enrolled onthis protocol must also agree to use adequate contraception prior to the study, forthe duration of study participation, and 6 months after completion of ZEN003694 (ZEN-3694) and capecitabine administration

• Ability to understand and the willingness to sign a written informed consentdocument. Legally authorized representatives may sign and give informed consent onbehalf of study participants

Exclusion Criteria:

• Previous treatment with BET inhibitors

• History of inability to tolerate capecitabine at the projected treatment dose onthis trial

• Use of oral Factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxabanotamixaban, letaxaban, eribaxaban) and Factor IIa inhibitors (i.e., dabigatran). Lowmolecular weight heparin is allowed

• Treatment for HIV, hepatitis B or hepatitis C only if this interferes with thecurrent treatment (e.g. through drug-drug interactions)

• Gastrointestinal pathology or history that adversely impacts the ability to take orabsorb oral medication

• Hepatic tumor burden > 30% or peritoneal carcinomatosis

• Untreated/uncontrolled central nervous system (CNS) disease

• Known dihydropyrimidine dehydrogenase (DPD) deficiency

• Severe intercurrent illness or comorbidity

• Inability to comply with the protocol and/or not willing or who will not beavailable for follow-up assessments

• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia andneuropathy up to and including grade 2

• Patients who are receiving any other investigational agents

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to ZEN003694 (ZEN-3694) or other agents used in study

• Patients receiving any medications or substances that are strong inhibitors orinducers of CYP3A4 are ineligible. Strong inhibitors of CYP3A4 must be discontinuedat least 7 days, and inducers 14 days prior to the first dose of ZEN003694 andcapecitabine. Substrates of CYP1A2 with narrow therapeutic window must be avoidedwhile taking ZEN003694

• Pregnant women are excluded from this study because ZEN003694 (ZEN-3694) is an agentwith the potential for teratogenic or abortifacient effects. Because there is anunknown but potential risk for adverse events in nursing infants secondary totreatment of the mother with ZEN003694 (ZEN-3694), breastfeeding should bediscontinued if the mother is treated with ZEN003694 (ZEN-3694). These potentialrisks may also apply to other agents used in this study