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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00535951
First received: September 26, 2007
Last updated: November 26, 2012
Last verified: November 2012
  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 1

Study Type: Interventional
Study Design: 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:


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:

  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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00535951     History of Changes
Other Study ID Numbers: CLBH589B2109
Study First Received: September 26, 2007
Last Updated: November 26, 2012
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, Non-Small-Cell Lung
Mesothelioma
Neoplasms, Mesothelial
Adenoma
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Lung Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Dextromethorphan
Panobinostat
Antineoplastic Agents
Antitussive Agents
Central Nervous System Agents
Enzyme Inhibitors
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014