Panobinostat and Epirubicin in Treating Patients With Metastatic Malignant Solid Tumors

Inclusion Criteria

• •DISEASE CHARACTERISTICS:
• •Cytologically or histologically confirmed solid tumor malignancy for which no curative therapy exists
• •* Metastatic disease
• •Measurable or evaluable disease (i.e., elevated CA-125 or elevated PSA for patients with ovarian cancer or prostate cancer, respectively)
• •Disease amenable to biopsy AND patient willing to undergo biopsies (for patients enrolled in the dose expansion cohort only)
• •No uncontrolled CNS metastasis
• •* Stable CNS metastasis allowed provided patient has undergone complete surgical resection, gamma knife radiotherapy (for isolated lesions) or whole-brain radiotherapy AND the metastasis has been stable for ≥ 6 weeks
• •PATIENT CHARACTERISTICS:
• •ECOG performance status 0-2
• •WBC \> 3,000/mm³
• •ANC \> 1,500/mm³
• •Hemoglobin \> 9.0 g/dL (RBC transfusion allowed)
• •Platelet count \> 100,000/mm³
• •AST/ALT ≤ 1.5 times upper limit of normal (ULN)
• •Serum bilirubin ≤ 1.3 times ULN
• •Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min by 24-hour urine collection
• •Total serum calcium (corrected for serum albumin) or ionized calcium ≥ lower limit of normal
• •Serum potassium ≥ 4.0 mEq/L (supplementation allowed)
• •Serum magnesium normal (supplementation allowed)
• •Serum sodium ≥ 130 mEq/L
• •Serum albumin ≥ 3 g/dL
• •Elevated alkaline phosphatase or gamma-glutamyl-transferase due to bone metastasis or liver metastasis allowed
• •Not pregnant or nursing
• •Negative pregnancy test
• •Fertile patients must use effective double-method (including barrier) contraception during and for 3 months after completion of study treatment
• •QTc \< 460 ms
• •No evidence of significant active infection (e.g., pneumonia, cellulitis, or wound abscess)
• •No impaired cardiac function, including any of the following:
• •* Complete left bundle branch block or use of a permanent cardiac pacemaker
• •* Congenital long QT syndrome
• •* History or presence of ventricular tachyarrhythmias
• •* Clinically significant resting bradycardia (\< 50 beats per minute)
• •* QTcF \> 470 msec on screening ECG
• •* Right bundle branch block plus left anterior hemiblock (bifascicular block)
• •* Atrial fibrillation (ventricular heart rate \> 100 beats per minute)
• •* Angina pectoris or acute myocardial infarction within the past 6 months
• •* New York Heart Association class III-IV congestive heart failure
• •* LVEF \< 50% on baseline MUGA or ECHO
• •No history of seizures
• •PRIOR CONCURRENT THERAPY:
• •No prior cumulative anthracycline dose \> 300 mg/m² of doxorubicin hydrochloride or \> 480 mg/m² of epirubicin hydrochloride
• •More than 5 days since prior valproic acid
• •More than 3 weeks since prior and no other concurrent chemotherapy, hormonal therapy, radiotherapy, or experimental anticancer therapy for the primary disease
• •No other concurrent HDAC inhibitors
• •No concurrent medications that may induce torsades de pointes or cause QTc prolongation
• •No other concurrent investigational or anticancer therapy
• •No concurrent CYP3A4 inhibitors (including grapefruit or grapefruit juice) and/or CYP3A4 inducers
• •No concurrent anti-arrhythmic therapy