Pharmacokinetic, Safety, and Efficacy Effects of Oral LBH589 on Dextromethorphan in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer or Malignant Pleural Mesothelioma

Novartis

Status and phase: Completed; Phase 1

Conditions: Carcinoma, Non-Small-Cell Lung; Mesothelioma

Treatments: Drug: LBH589

Study type: Interventional

Funder types: Industry

Identifiers

NCT00535951

CLBH589B2109

Details and patient eligibility

About

This study will investigate the effect of oral LBH589 on dextromethorphan, a CYP2D6 substrate, and to assess safety and efficacy of oral LBH589 when used with this co-medication in advanced stage NSCLC or malignant pleural mesothelioma patients

Enrollment: 18 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥ 18 years
2. Must have histologically or cytologically confirmed advanced or metastatic incurable solid tumor as documented by CT or MRI that has progressed on or following standard therapies
3. Must have failed prior standard systemic therapy
4. Must have at least one measurable and/or non-measurable lesion as defined by RECIST criteria
5. Baseline MUGA or ECHO must demonstrate LVEF ≥ the lower limit of the institutional normal.
6. Written informed consent obtained prior to any screening procedures
7. Willingness to have multiple blood draws
8. Ability to swallow capsules or tablets

Exclusion criteria

1. Uncontrolled brain metastases
2. Prior treatment with an HDAC inhibitor
3. Presence of clinically detectable third-space fluid collections (e.g., ascites or pleural effusions) that can not be controlled by drainage or other procedures prior to study entry
4. Concomitant use of any anti-cancer therapy, including radiation therapy
5. Significant cardiac disease
6. Concomitant use of drugs with a risk of causing torsades de pointes
7. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589
8. Previous use of monoamine oxidase inhibitors (e.g. clorgyline, iproniazid, isocarboxazid, moclobemide, sibutramine, phenelzine, tranylcypromine) within 14 days prior to the first dose of dextromethorphan

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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18 participants in 1 patient group

LBH589

Experimental group

Treatment:

Drug: LBH589