Panobinostat and Epirubicin in Treating Patients With Metastatic Malignant Solid Tumors

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