Phase I Trial of Cisplatin and Pemetrexed in Combination With Panobinostat in Advanced Solid Tumors, With Emphasis on Non-Small Cell Lung Cancer
- 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:
- Neutrophil count of ≥ 1.5 x 109/L
- Platelet count of ≥ 100 x 109/L
- Hemoglobin ≥ 9 g/dL
- 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
- 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
- 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
- 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