Study to Evaluate Panobinostat (DACi) Pharmacokinetics and Safety in Solid Tumors and Varying Renal Function

Phase 1

Completed

• Conditions: Advanced Solid Tumors
• Interventions: Drug: panobinostat (LBH589)

• Registration Number: NCT00997399
• Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-10-15
• Study First Submitted QC: 2009-10-16
• Study First Posted: 2009-10-19
• Study Start: 2010-03
• Primary Completion: 2014-06
• Study Completion: 2014-06
• Status Verified: 2019-07
• Last Update Submitted: 2020-12-16
• Last Update Posted: 2020-12-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 37

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LBH589	panobinostat (LBH589)	-

Primary Outcome Measures

Name	Time	Method
To assess the effect of varying degrees of renal function as defined by creatinine clearance), on the pharmacokinetics of panobinostat.	First 7 days

Secondary Outcome Measures

Name	Time	Method
To assess the effect of varying degrees of renal function on the safety of panobinostat	Entire duration of study
To evaluate whether there is a relationship between PK and safety parameters in patients with varying degrees of renal function.	7 days
To explore anti-tumor activity associated with panobinostat.	6 months (6 cycles)

Trial Locations

Locations (2)

University of Utah / Huntsman Cancer Institute; 🇺🇸 Salt Lake City, Utah, United States

Novartis Investigative Site; 🇬🇧 Merseyside, United Kingdom