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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT00997399

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

7.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Drug: panobinostat (LBH589)	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

37 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Study Start Date :

Mar 1, 2010

Actual Primary Completion Date :

Jun 1, 2014

Actual Study Completion Date :

Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LBH589	Drug: panobinostat (LBH589)

Arm

Intervention/Treatment

Experimental: LBH589

Drug: panobinostat (LBH589)

Outcome Measures

Primary Outcome Measures

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

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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Utah / Huntsman Cancer Institute	Salt Lake City	Utah	United States	84103
2	Novartis Investigative Site	Leiden		Netherlands	2300 RC
3	Novartis Investigative Site	Utrecht		Netherlands	3584CX
4	Novartis Investigative Site	St. Gallen		Switzerland	9007
5	Novartis Investigative Site	Merseyside		United Kingdom	L63 4JY