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

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”

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

Intervention(s) in this Clinical Trial

• Drug: LBH589

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: LBH589

Primary Measures

• Pharmacokinetic (PK) parameters
  • Time Frame: first 10 days
    Safety Issue?: Yes

Secondary Measures

• Response rate assessed by comparing tumor size via radiology scans (CTs or MRIs)
  • Time Frame: day 10 through end of treatment
    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
    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
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Novartis Pharmaceuticals Industry

Overall Clinical Trial Officials and Contacts

Novartis Pharmaceuticals Study Director Novartis Pharmeceuticals  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00535951

Study ID Number: CLBH589B2109

ClinicalTrials.gov Identifier: NCT00535951

Health Authority: Canada: Health Canada (Sante Canada)