Clinical trial NCT00535951: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma, Non-Small-Cell Lung
Mesothelioma
Keywords: Non-small cell lung cancer
NSCLC
lung cancer
pleural mesothelioma
malignant
advanced stage
mesothelioma
phase I
LBH589
dextromethorphan
CYP2D6
oral
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2007-09-27
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: Pharmacokinetic (PK) parameters
timeFrame: first 10 days
Secondary outcomes:
measure: Response rate assessed by comparing tumor size via radiology scans (CTs or MRIs)
timeFrame: day 10 through end of treatment
measure: Safety (until disease progression, unacceptable toxicity or study completion) assessed by duration of patient participation
timeFrame: first 10 days, day 10 through end of treatment plus follow-up
measure: Tolerability (until disease progression, unacceptable toxicity or study completion) assessed by duration of patient participation
timeFrame: day 10 through end of treatment
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Chicago
country: United States
facility: RUSH Medical Center
state: Illinois
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Ontario
country: Canada
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmeceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: