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

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: LBH589

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient has documented diagnosis of advanced solid tumor for which no standard systemic therapy exists
2. Patient has normal or abnormal hepatic organ function
3. Patient has provided written informed consent prior to any screening procedures

Exclusion Criteria:

1. Patient needing valproic acid for any medical condition during the study or within 5 days prior to the first panobinostat dose
2. Patient received prior treatment with DAC inhibitors including panobinostat
3. Patient requires treatment with warfarin that cannot be switched to another anticoagulant treatment prior to starting study drug
4. Patient has encephalopathy
5. Patient has ascites requiring intervention
6. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HDACi	Drug: LBH589

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Slingerland M, Hess D, Clive S, Sharma S, Sandstrom P, Loman N, Porro MG, Mu S, Waldron E, Valera SZ, Gelderblom H. 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. Cancer Chemother Pharmacol. 2014 Nov;74(5):1089-98. doi: 10.1007/s00280-014-2594-6. Epub 2014 Sep 25.

Helpful Links

• Results for CLBH589X2101 on the Novartis clinical trial website

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: October 28, 2009
• First Submitted That Met QC Criteria: November 4, 2009
• First Posted (Estimate): November 5, 2009

Study Record Updates

• Last Update Posted (Actual): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: solid tumors; advanced; panobinostat; hepatic function
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Histone Deacetylase Inhibitors; Panobinostat
• Other Study ID Numbers: CLBH589X2101; 2009-012262-31 (EudraCT Number)