Clinical trial NCT01007968: Pharmacokinetics and Safety of Panobinostat in Patients With Advanced Solid Tumors and Various Degrees of Hepatic Function
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: solid tumors
hepatic function
advanced
panobinostat
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-11-05
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: first 7 days
Secondary outcomes:
measure: To assess the effect of various degrees of impairment in hepatic function on the safety of panobinostat
timeFrame: entire duration of study
measure: To evaluate whether there is a relationship between panobinostat PK and safety parameters in patients with various degrees of hepatic organ function
timeFrame: first 7 days
measure: To explore anti-tumor activity associated with panobinostat.
timeFrame: best overall response
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: University of Utah / Huntsman Cancer Institute
state: Utah
city: Leiden
country: Netherlands
facility: Novartis Investigative Site
city: Lund
country: Sweden
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: St. Gallen
country: Switzerland
facility: Novartis Investigative Site
city: Edinburgh
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.