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

Novartis

Status and phase: Completed; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: LBH589

Study type: Interventional

Funder types: Industry

Identifiers

NCT01007968

2009-012262-31 (EudraCT Number)

CLBH589X2101

Details and patient eligibility

About

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.

Enrollment: 25 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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25 participants in 1 patient group

HDACi

Experimental group

Treatment:

Drug: LBH589