Panobinostat, Etoposide, and Cisplatin as First-Line Therapy in Treating Patients With Extensive-Stage Small Cell Lung Cancer
RATIONALE: Panobinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as etoposide and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving panobinostat together with etoposide and cisplatin may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of panobinostat when given together with etoposide and cisplatin as first-line therapy in treating patients with extensive-stage small cell lung cancer.
Drug: etoposide phosphate
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Dose Finding Study of the Pan-DAC Inhibitor Panobinostat (LBH589) in Combination With Etoposide and Cisplatin in the First Line Treatment of Extensive-Stage Small Cell Lung Cancer - An ICORG In-House Study|
- Maximum-tolerated dose (MTD) and recommended dose (RD) [ Designated as safety issue: No ]
- Response rates and toxicity at MTD and RD [ Designated as safety issue: Yes ]
- Objective response rate according to RECIST criteria [ Designated as safety issue: No ]
- Time to progression according to RECIST criteria [ Designated as safety issue: No ]
- Duration of response or disease stabilization according to RECIST criteria [ Designated as safety issue: No ]
- Overall survival according to RECIST criteria [ Designated as safety issue: No ]
- Effect of the combination regimen on drug pharmacokinetics [ Designated as safety issue: No ]
- Adverse events [ Designated as safety issue: Yes ]
- Quality of life evaluated by EQ-5D (Euro QoL) [ Designated as safety issue: Yes ]
|Study Start Date:||November 2009|
|Primary Completion Date:||October 2010 (Final data collection date for primary outcome measure)|
|Experimental: Cisplatin, Etoposide & Panobinostat||Drug: cisplatin Drug: etoposide phosphate Drug: panobinostat Other: laboratory biomarker analysis Other: pharmacological study|
- To determine the maximum-tolerated dose, the recommended dose, and the activity of panobinostat when given in combination with etoposide and cisplatin to patients with extensive-stage small cell lung cancer.
- To estimate the time-to-progression, the duration of response, and disease stabilization in these patients.
- To estimate the overall survival of these patients.
- To determine the pharmacokinetic profile of panobinostat in combination with etoposide and cisplatin.
- To assess the overall safety profile of panobinostat in these patients.
- To determine the adverse events in these patients treated with this regimen.
- To assess the quality of life of these patients.
OUTLINE: This is a multicenter, dose-escalation study of panobinostat.
Patients receive chemotherapy comprising cisplatin IV on day 1, etoposide IV on days 1-3, and panobinostat IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline and then periodically during study treatment and follow up, using questionnaire EQ-5D (Euro QoL).
Blood samples may be collected at baseline and periodically during and after study treatment for pharmacokinetic assessment and biomarker translational studies.
After completion of study treatment, patients are followed up at 4 weeks and then every 3 months.