Pharmacokinetics and Safety of Panobinostat in Patients With Advanced Solid Tumors and Various Degrees of Hepatic Function

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01007968

Collaborator

(none)

Enrollment

Locations

Arm

32.1

Duration (Months)

4.2

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 hepatic function status on panobinostat PK.

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

Study Design

Study Type:

Interventional

Actual Enrollment :

25 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

A Phase I, Open-label, Multicenter Study to Evaluate the Pharmacokinetics and Safety of Oral Panobinostat in Patients With Advanced Solid Tumors and Various Degrees of Hepatic Function

Study Start Date :

Mar 1, 2010

Actual Primary Completion Date :

Nov 1, 2012

Actual Study Completion Date :

Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HDACi	Drug: LBH589

Arm

Intervention/Treatment

Experimental: HDACi

Drug: LBH589

Outcome Measures

Primary Outcome Measures

To assess the effect of various degrees of impairment in hepatic function as measured by the National Cancer Institute-Cancer Therapy Evaluation Program (NCI-CTEP) criteria, on the pharmacokinetics of panobinostat. [first 7 days]

Secondary Outcome Measures

To assess the effect of various degrees of impairment in hepatic function on the safety of panobinostat [entire duration of study]
To evaluate whether there is a relationship between panobinostat PK and safety parameters in patients with various degrees of hepatic organ function [first 7 days]
To explore anti-tumor activity associated with panobinostat. [best overall response]

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 hepatic 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 requires treatment with warfarin that cannot be switched to another anticoagulant treatment prior to starting study drug
Patient has encephalopathy
Patient has ascites requiring intervention
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	Lund		Sweden	SE-221 85
4	Novartis Investigative Site	Stockholm		Sweden	SE-171 76
5	Novartis Investigative Site	St. Gallen		Switzerland	9007
6	Novartis Investigative Site	Edinburgh		United Kingdom	EH4 2XR