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 - Full Text View

Sponsor:	Novartis Pharmaceuticals
Information provided by:	Novartis
ClinicalTrials.gov Identifier:	NCT00535951

Purpose

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	Intervention	Phase
Carcinoma, Non-Small-Cell Lung Mesothelioma	Drug: LBH589	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer Mesothelioma

Drug Information available for: Dextromethorphan hydrochloride LBH589 Levomethorphan Dextromethorphan Racemethorphan Dextromethorphan hydrobromide

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Pharmacokinetic (PK) parameters [ Time Frame: first 10 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Response rate assessed by comparing tumor size via radiology scans (CTs or MRIs) [ Time Frame: day 10 through end of treatment ] [ Designated as safety issue: No ]
Safety (until disease progression, unacceptable toxicity or study completion) assessed by duration of patient participation [ Time Frame: first 10 days, day 10 through end of treatment plus follow-up ] [ Designated as safety issue: Yes ]
Tolerability (until disease progression, unacceptable toxicity or study completion) assessed by duration of patient participation [ Time Frame: day 10 through end of treatment ] [ Designated as safety issue: Yes ]

Enrollment:	18
Study Start Date:	November 2007
Primary Completion Date:	January 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: LBH589	Drug: LBH589

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00535951

Locations

United States, Arkansas
Highlands Oncology Group
Fayetteville, Arkansas, United States, 72703
United States, Georgia
Medical College of Georgia
Augusta, Georgia, United States, 30912
United States, Illinois
RUSH Medical Center
Chicago, Illinois, United States, 60612
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Canada
Novartis Investigative Site
Ontario, Canada

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

Novartis Pharmeceuticals

More Information

No publications provided

Responsible Party:	External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00535951 History of Changes
Other Study ID Numbers:	CLBH589B2109
Study First Received:	September 26, 2007
Last Updated:	January 14, 2010
Health Authority:	Canada: Health Canada (Sante Canada); United States: Food and Drug Administration

Keywords provided by Novartis:

Non-small cell lung cancer
NSCLC
lung cancer
pleural mesothelioma
malignant
advanced stage
mesothelioma

phase I
LBH589
dextromethorphan
CYP2D6
oral
Non-small Cell Lung Cancer
Pleural Mesothelioma

Additional relevant MeSH terms:

Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Mesothelioma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases

Adenoma
Neoplasms, Mesothelial
Dextromethorphan
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antitussive Agents
Central Nervous System Agents
Therapeutic Uses
Respiratory System Agents

ClinicalTrials.gov processed this record on February 09, 2012