Study to Evaluate Panobinostat (DACi) Pharmacokinetics and Safety in Solid Tumors and Varying Renal 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 renal function status on panobinostat PK.

Condition	Intervention	Phase
Advanced Solid Tumors	Drug: panobinostat (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, Multi-center Study to Evaluate the Pharmacokinetics and Safety of Oral Panobinostat in Patients With Advanced Solid Tumors and Varying Degrees of Renal 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 varying degrees of renal function as defined by creatinine clearance), on the pharmacokinetics of panobinostat. [ Time Frame: First 7 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To assess the effect of varying degrees of renal function on the safety of panobinostat [ Time Frame: Entire duration of study ] [ Designated as safety issue: Yes ]
To evaluate whether there is a relationship between PK and safety parameters in patients with varying degrees of renal function. [ Time Frame: 7 days ] [ Designated as safety issue: No ]
To explore anti-tumor activity associated with panobinostat. [ Time Frame: 6 months (6 cycles) ] [ Designated as safety issue: No ]

Estimated Enrollment:	37
Study Start Date:	February 2010
Estimated Study Completion Date:	June 2014
Estimated Primary Completion Date:	May 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: LBH589	Drug: panobinostat (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 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00997399

Contacts

Contact: Novartis Pharmaceuticals	1-888-669-6682
Contact: Novartis Pharmaceuticals

Locations

United States, Utah
University of Utah / Huntsman Cancer Institute	Recruiting
Salt Lake City, Utah, United States, 84103
Contact: Daniel Grissom 801-587-5597 Daniel.Grissom@hci.utah.edu
Principal Investigator: Sunil Sharma
Netherlands
Novartis Investigative Site	Completed
Leiden, Netherlands, 2300 RC
Novartis Investigative Site	Completed
Utrecht, Netherlands, 3584CX
Sweden
Novartis Investigative Site	Withdrawn
Stockholm, Sweden, 171 76
Switzerland
Novartis Investigative Site	Completed
St. Gallen, Switzerland, 9007
United Kingdom
Novartis Investigative Site	Active, not recruiting
Merseyside, United Kingdom, L63 4JY

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT00997399 History of Changes
Other Study ID Numbers:	CLBH589X2105, 2009-012263-34
Study First Received:	October 15, 2009
Last Updated:	April 15, 2013
Health Authority:	United States: Food and Drug Administration Switzerland: Swissmedic Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Novartis:

Ph I
panobinostat (DACi)
PK & safety

solid tumors
varying renal function
advanced

Additional relevant MeSH terms:

Neoplasms

ClinicalTrials.gov processed this record on May 19, 2013