Safety, Tolerability and Pharmacokinetics of Quisinostat, a Histone Deacetylase Inhibitor, in Combination With Chemotherapy

Exclusion Criteria

• •1. Indications for X-ray therapy or chemoradiation therapy at the time of inclusion, regardless of the treated area;
• •2. Presence of clinical and/or radiological signs of metastases in the brain and meningeal structures (CNS);
• •3. Previous therapy with HDAC inhibitors
• •4. Any contraindications to the chemotherapy with Gemcitabine + Cisplatin or Paclitaxel + Carboplatin (in patients with lung cancer); contraindications to chemotherapy according to the standard chemotherapy combination scheme Paclitaxel + Carboplatin (in female patients with ovarian cancer);
• •5. Any contraindications to administration of glucocorticosteroids, antihistamine drugs, serotonin 5-HT3 receptor antagonists, aprepitant;
• •6. Any contraindications to forced rehydration and/or administration of forced diuresis (in case of lung cancer);
• •7. Conditions that require continuous use of oral anticoagulants, or clinically significant changes in blood coagulation parameters at screening (INR \> 1.5, aPTT\> 1.5 х ULN)
• •8. Conditions that require admission of prohibited drugs, or impossibility to replace those with allowed drugs in the study
• •9. Current infection or other systemic conditions constituting a contraindication to the intended chemotherapy;
• •10. Diseases of the digestive system which may infringe absorption of the investigational product (Crohn's disease, nonspecific ulcerative colitis, irritable bowel syndrome)
• •11. Clinically significant cardiovascular diseases including:
• •* Myocardial infarction within 12 months before screening
• •* Unstable angina within 12 months before screening
• •* Congestive heart failure Class III or IV according to the New York Heart Association criteria (NYHA)
• •* Clinically significant ventricular arrhythmia including ventricular tachycardia, ventricular fibrillation, history of cardiac arrest, atrioventricular block (Mobitz II or III), use of cardiostimulator
• •* QTc interval \> 450 ms in men or 470 ms in women (ECG) (calculated according to Fredericia formula), or a diagnosis of long QT syndrome
• •* Hypotension (systolic blood pressure \< 86 mm Hg or bradycardia with a heart rate of \< 50 beats per minute (ECG) except when caused by medications (e.g. beta-blockers).
• •* Uncontrolled arterial hypertension (systolic arterial pressure \> 170 millimeters of mercury or diastolic blood pressure \> 105 millimeters of mercury)
• •12. Pregnancy and lactation
• •13. Presence of HIV antibodies, Hepatitis В and С antibodies
• •14. Drug or alcohol abuse at the moment of screening or in the past which according to the opinion of the Investigator makes the patient unsuitable for participation in the study
• •15. Significant allergic reactions in medical history
• •16. Participation in other clinical studies or administration of test drugs during 30 days before beginning of the study or persisting side effect of any of the test drugs;
• •17. Toxic effects of previous treatments or complications after surgical treatments that did not resolve to grades 1 and/or 0 (according to the CTCAE scale).
• •18. Patient not willing to participate in the study or unable to understand or follow the protocol instructions.