Study of Cisplatin and Pemetrexed in Combination With Panobinostat in Solid Tumors

Inclusion Criteria:

• Histological or cytological proven advanced solid tumors for which curative standard treatments are not available.
• Must have measurable or evaluable disease.
• Male or female patients aged ≥ 18 years old.
• Any number of prior chemotherapy regimens.
• ECOG Performance Status of ≤ 2 with a life expectancy greater than 3 months.
• Clinically euthyroid (may be on thyroid hormone replacement)
• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of study treatment.
• Ability to provide written informed consent
• Must meet the following laboratory criteria:

Hematology:

• Neutrophil count of ≥ 1.5 x 109/L
• Platelet count of ≥ 100 x 109/L
• Hemoglobin ≥ 9 g/dL

Biochemistry:

• AST/SGOT and ALT/SGPT ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if the transaminase elevation is due to disease involvement
• Serum bilirubin ≤ 1.5 x ULN
• Serum creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 50 ml/min
• Total serum calcium (corrected for serum albumin) or ionized calcium ≥ LLN and ≤ ULN
• Serum potassium ≥ LLN and ≤ ULN
• Serum sodium ≥ LLN and ≤ ULN
• Serum albumin ≥ LLN or 3g/dl
• Serum magnesium ≥ LLN and ≤ ULN
• Any elevated Alkaline Phosphatase due to bone metastasis can be enrolled

Exclusion Criteria:

• Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer.
• Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment.
• Patients who have received chemotherapy, any investigational drug or undergone major surgery < 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
• Impaired cardiac function
• Other concurrent severe and/or uncontrolled medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol
• Concomitant use of drugs which are generally recognized to have a risk of causing torsades de pointes where such treatment cannot be discontinued or switched to a different medication prior to starting study drug
• Patients with unresolved diarrhea ≥ CTCAE grade 2
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobinostat. Inability to swallow panobinostat capsules whole.
• Concomitant use of any anti-cancer therapy or radiation therapy
• Uncontrolled or symptomatic brain metastases.
• Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not willing to use a double barrier method of contraception during the study and 3 months after the end of treatment. One of these methods of contraception must be a barrier method. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months).
• Male patients whose sexual partners are WOCBP not using a double method of contraception during the study and 3 months after the end of treatment.
• Known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required
• Any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent