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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT00535951

Collaborator

(none)

Enrollment

Locations

Arm

3.6

Patients Per Site

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small-Cell Lung Mesothelioma	Drug: LBH589	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase IB, Open-Label, Multicenter Study to Investigate the Effect of Oral LBH589 on Dextromethorphan, a CYP2D6 Substrate, and to Assess the Efficacy and Safety of Oral LBH589 in Patients With Advanced Solid Tumors

Study Start Date :

Nov 1, 2007

Actual Primary Completion Date :

Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LBH589	Drug: LBH589

Arm

Intervention/Treatment

Experimental: LBH589

Drug: LBH589

Outcome Measures

Primary Outcome Measures

Pharmacokinetic (PK) parameters [first 10 days]

Secondary Outcome Measures

Response rate assessed by comparing tumor size via radiology scans (CTs or MRIs) [day 10 through end of treatment]
Safety (until disease progression, unacceptable toxicity or study completion) assessed by duration of patient participation [first 10 days, day 10 through end of treatment plus follow-up]
Tolerability (until disease progression, unacceptable toxicity or study completion) assessed by duration of patient participation [day 10 through end of treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

Age ≥ 18 years
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
Must have failed prior standard systemic therapy
Must have at least one measurable and/or non-measurable lesion as defined by RECIST criteria
Baseline MUGA or ECHO must demonstrate LVEF ≥ the lower limit of the institutional normal.
Written informed consent obtained prior to any screening procedures
Willingness to have multiple blood draws
Ability to swallow capsules or tablets

Exclusion criteria:

Uncontrolled brain metastases
Prior treatment with an HDAC inhibitor
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
Concomitant use of any anti-cancer therapy, including radiation therapy
Significant cardiac disease
Concomitant use of drugs with a risk of causing torsades de pointes
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Highlands Oncology Group	Fayetteville	Arkansas	United States	72703
2	Medical College of Georgia	Augusta	Georgia	United States	30912
3	RUSH Medical Center	Chicago	Illinois	United States	60612
4	MD Anderson Cancer Center	Houston	Texas	United States	77030
5	Novartis Investigative Site	Ontario		Canada