Carcinoma, Non-Small-Cell Lung, Mesothelioma
Conditions
Keywords
Non-small cell lung cancer, NSCLC, lung cancer, pleural mesothelioma, malignant, advanced stage, mesothelioma, phase I, LBH589, dextromethorphan, CYP2D6, oral
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
Interventions
DRUGLBH589
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetic (PK) parameters | first 10 days |
Secondary
| Measure | Time frame |
|---|---|
| Response rate assessed by comparing tumor size via radiology scans (CTs or MRIs) | day 10 through end of treatment |
| 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 |
| Tolerability (until disease progression, unacceptable toxicity or study completion) assessed by duration of patient participation | day 10 through end of treatment |
Countries
Canada, United States
Outcome results
None listed