Phase I Trial of Cisplatin and Pemetrexed in Combination With Panobinostat in Advanced Solid Tumors, With Emphasis on Non-Small Cell Lung Cancer

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