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

Carcinoma, Non-Small-Cell Lung Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00535951
• Other study ID #: CLBH589B2109
• Status: Completed
• Phase: Phase 1
• Start date: November 2007

Study information

• Verified date: November 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Mesothelioma

Intervention

Drug:
• LBH589

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Ontario
United States	Medical College of Georgia	Augusta	Georgia
United States	RUSH Medical Center	Chicago	Illinois
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	MD Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic (PK) parameters		first 10 days
Secondary	Response rate assessed by comparing tumor size via radiology scans (CTs or MRIs)		day 10 through end of treatment
Secondary	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
Secondary	Tolerability (until disease progression, unacceptable toxicity or study completion) assessed by duration of patient participation		day 10 through end of treatment

External Links

•   Results for CLBH589B2109 can be found on the Novartis Clinical Trial Results Website