Study to Evaluate Panobinostat (DACi) Pharmacokinetics and Safety in Solid Tumors and Varying Renal Function

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I, Open-label, Multi-center Study to Evaluate the Pharmacokinetics and Safety of Oral Panobinostat in Patients With Advanced Solid Tumors and Varying Degrees of Renal Function

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: panobinostat (LBH589)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has documented diagnosis of advanced solid tumor for which no standard systemic therapy exists Patient has normal or abnormal renal organ function Patient has provided written informed consent prior to any screening procedures Exclusion Criteria: Patient needing valproic acid for any medical condition during the study or within 5 days prior to the first panobinostat dose Patient received prior treatment with DAC inhibitors including panobinostat Patient requiring dialysis Patient requiring diuretics unless patient is taking potassium sparring diuretics Patient has acute renal failure, history of transplant, ESRD (however acceptable severe renal impaired group) 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/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LBH589<br> | Drug: panobinostat (LBH589)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ph I, panobinostat (DACi), PK & safety, solid tumors, varying renal function, advanced