Advanced Solid Tumors
Conditions
Keywords
Ph I, panobinostat (DACi), PK & safety, solid tumors, varying renal function, advanced
Brief summary
Panobinostat (LBH589) is a deacetylase inhibitor (DACi) which belongs to a structurally novel cinnamic hydroxamic acid class of compounds. It is one of the most potent class I/II pan-DAC inhibitor (pan-DACi) that has shown anti-tumor activity in pre-clinical models and patients with solid tumors and hematological malignancies. To date, the pharmacokinetics (PK) of panobinostat has been characterized in patients with solid tumors and hematological malignancies participating in several phase I/II clinical studies. Panobinostat PK does not appear to be different in patients with solid tumors and hematological malignancies. However, the effect of organ dysfunction on PK of panobinostat is yet to be elucidated. Kidney and liver are involved in the elimination and metabolism of panobinostat. The current study is designed to evaluate the impact of renal function status on panobinostat PK.
Interventions
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient has documented diagnosis of advanced solid tumor for which no standard systemic therapy exists 2. Patient has normal or abnormal renal organ function 3. Patient has provided written informed consent prior to any screening procedures
Exclusion criteria
1. Patient needing valproic acid for any medical condition during the study or within 5 days prior to the first panobinostat dose 2. Patient received prior treatment with DAC inhibitors including panobinostat 3. Patient requiring dialysis 4. Patient requiring diuretics unless patient is taking potassium sparring diuretics 5. Patient has acute renal failure, history of transplant, ESRD (however acceptable severe renal impaired group) 6. Female patient who is pregnant or breast feeding or with childbearing potential and not willing to use a double method of contraception up to 3 months after the end of study treatment. Male patient who is not willing to use a barrier method of contraception up to 3 months after the end of study treatment. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the effect of varying degrees of renal function as defined by creatinine clearance), on the pharmacokinetics of panobinostat. | First 7 days |
Secondary
| Measure | Time frame |
|---|---|
| To assess the effect of varying degrees of renal function on the safety of panobinostat | Entire duration of study |
| To evaluate whether there is a relationship between PK and safety parameters in patients with varying degrees of renal function. | 7 days |
| To explore anti-tumor activity associated with panobinostat. | 6 months (6 cycles) |
Countries
Netherlands, Switzerland, United Kingdom, United States
Outcome results
None listed