Clinical trial NCT00997399: Study to Evaluate Panobinostat (DACi) Pharmacokinetics and Safety in Solid Tumors and Varying Renal Function
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Ph I
panobinostat (DACi)
PK & safety
solid tumors
varying renal function
advanced
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-10-19
Enrollment: 37
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 renal 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 renal 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 requiring dialysis
4. Patient requiring diuretics unless patient is taking potassium sparring diuretics
5. Patient has acute renal failure, history of transplant, ESRD (however acceptable severe renal impaired group)
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 varying degrees of renal function as defined by creatinine clearance), on the pharmacokinetics of panobinostat.
timeFrame: First 7 days
Secondary outcomes:
measure: To assess the effect of varying degrees of renal function on the safety of panobinostat
timeFrame: Entire duration of study
measure: To evaluate whether there is a relationship between PK and safety parameters in patients with varying degrees of renal function.
timeFrame: 7 days
measure: To explore anti-tumor activity associated with panobinostat.
timeFrame: 6 months (6 cycles)
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: Utrecht
country: Netherlands
facility: Novartis Investigative Site
city: St. Gallen
country: Switzerland
facility: Novartis Investigative Site
city: Merseyside
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Sharma S, Witteveen PO, Lolkema MP, Hess D, Gelderblom H, Hussain SA, Porro MG, Waldron E, Valera SZ, Mu S. A phase I, open-label, multicenter study to evaluate the pharmacokinetics and safety of oral panobinostat in patients with advanced solid tumors and varying degrees of renal function. Cancer Chemother Pharmacol. 2015 Jan;75(1):87-95. doi: 10.1007/s00280-014-2612-8. Epub 2014 Nov 7.