Pharmacokinetics and Safety of Panobinostat in Patients With Advanced Solid Tumors and Various Degrees of Hepatic Function - Full Text View

Purpose

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	Intervention	Phase
Advanced Solid Tumors	Drug: LBH589	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: Open Label
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by Novartis:

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. [ Time Frame: first 7 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To assess the effect of various degrees of impairment in hepatic function on the safety of panobinostat [ Time Frame: entire duration of study ] [ Designated as safety issue: No ]
To evaluate whether there is a relationship between panobinostat PK and safety parameters in patients with various degrees of hepatic organ function [ Time Frame: first 7 days ] [ Designated as safety issue: No ]
To explore anti-tumor activity associated with panobinostat. [ Time Frame: best overall response ] [ Designated as safety issue: No ]

Estimated Enrollment:	24
Study Start Date:	March 2010
Estimated Study Completion Date:	November 2012
Estimated Primary Completion Date:	November 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: HDACi	Drug: LBH589

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01007968

Locations

United States, Utah
University of Utah / Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84103
Netherlands
Novartis Investigative Site
Leiden, Netherlands, 2300 RC
Sweden
Novartis Investigative Site
Lund, Sweden, SE-221 85
Novartis Investigative Site
Stockholm, Sweden, SE-171 76
Switzerland
Novartis Investigative Site
St. Gallen, Switzerland, 9007
United Kingdom
Novartis Investigative Site
Edinburgh, United Kingdom, EH4 2XR

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT01007968 History of Changes
Other Study ID Numbers:	CLBH589X2101, EUDRACT number: 2009-012262-31
Study First Received:	October 28, 2009
Last Updated:	October 7, 2012
Health Authority:	United States: Food and Drug Administration Switzerland: Swissmedic United Kingdom: Medicines and Healthcare Products Regulatory Agency Sweden: Medical Products Agency Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by Novartis:

solid tumors
hepatic function
advanced
panobinostat

Additional relevant MeSH terms:

Neoplasms

ClinicalTrials.gov processed this record on May 21, 2013