ZEN003694 Combined With Niraparib in Patients With Metastatic or Recurrent Solid Tumors

Exclusion Criteria

• •Current or anticipated use of medications known to be strong inhibitors or inducers of CYP3A4 or substrates of CYP1A2 with narrow therapeutic windows. Strong inhibitors, inducers or substrates must be discontinued at least 7 days prior to the first administration of study drug.
• •Current or anticipated use within 7 days prior to the first administration of study drug, or during the study, of strong P-gp inhibitors.
• •Use of oral Factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban otamixaban, letaxaban, eribaxaban) and Factor IIa inhibitors (i.e., dabigatran). Low molecular weight heparin is allowed
• •Radiation to \>25% of the bone marrow
• •Treatment with a bone-targeted radionuclide within 6 weeks of first dose of study drug
• •Have previously received an investigational BET inhibitor (including previous participation in studies with Zenith drug, ZEN003694)
• •QTcF interval \> 470 msec
• •Insufficient recovery from prior treatment-related toxicities except for alopecia, fatigue and Grade 2 neuropathy
• •Non-healing wound, ulcer or bone fracture (not including a pathological bone fracture caused by a pre-existing pathological bone lesion)
• •Brain metastases not adequately treated and/or clinically stable (at the discretion of the Investigator) for at least 6 months prior to the start of study treatment.
• •Known impaired cardiac function or clinically significant cardiac disease such as uncontrolled supraventricular arrhythmia, ventricular arrhythmia requiring therapy, or congestive heart failure (New York Heart Association functional class III or IV)
• •Myocardial infarction or unstable angina within 6 months prior to the first administration of study drug
• •Known myelodysplastic syndrome
• •Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy, or any other condition that could compromise safety or the patient's participation in the study
• •Impairment of gastrointestinal function that may significantly alter the absorption of ZEN003694 or niraparib
• •Other known active cancer requiring therapy at time of study entry or that progressed or required treatment within 3 years prior to starting study drug (except for skin basal cell carcinoma or squamous cell carcinoma or in situ cervical cancer)
• •Prior history with PRES
• •Hypersensitivity to the active substance of to any of the excipients, including tartrazine in the capsule formulation.
• •Patients with not adequately controlled hypertension despite adequate medical treatment.
• •History of infection with (screening tests not required): human immunodeficiency virus; hepatitis B virus with currently active disease defined as hepatitis B surface antigen (HBsAg) positivity; or hepatitis C virus unless previously treated and viral load is undetectable except following situations:
• •* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of enrollment are eligible for this trial.
• •* Patients with a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection are allowed to be included if: participant on a stable dose of antiviral therapy, HBV viral load below the limit of quantification. HCV viral load below the limit of quantification.
• •Major surgery other than diagnostic surgery, dental surgery or stenting within 4 weeks prior to the first administration of study drug
• •Concurrent participation in another clinical investigational treatment trial
• •Any other reason that in the opinion of the Investigator would prevent the patient from completing participation or following the study schedule