Study of Cisplatin and Pemetrexed in Combination With Panobinostat in Solid Tumors
The purpose of this study is to find out if panobinostat taken with cisplatin and pemetrexed can be used safely without increasing side effects and that the combination will have a better effect than platinum-based doublet chemotherapy alone.
Non-Small Cell Lung Cancer (NSCLC)
Drug: Panobinostat, Cisplatin, Pemetrexed
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Trial of Cisplatin and Pemetrexed in Combination With Panobinostat in Advanced Solid Tumors, With Emphasis on Non-Small Cell Lung Cancer|
- Safety and feasibility of oral panobinostat in combination with cisplatin and pemetrexed [ Time Frame: Within ±3 days of the scheduled day of assessment except for adverse events that will be evaluated continuously through the study. The expected time frame for this outcome measure is 18 weeks (or six cycles) ] [ Designated as safety issue: Yes ]Safety assessments will consist of monitoring and recording all adverse events and serious adverse events, the regular monitoring of hematology, blood chemistry and urine values, regular measurement of vital signs and the performance of physical examination. Safety and tolerability will be assessed according to the NCI CTCAE v4.
- Maximum-tolerated dose as assessed by NCI CTCAE, Version 4.0 [ Time Frame: 3 week cycle; the expected time frame is 18 weeks (or 6 cycles) ] [ Designated as safety issue: Yes ]Determination of maximum tolerated dose (MTD) will be based on cycle 1 toxicities
- Dose-limiting toxicities and toxicity profile as assessed by NCI CTCAE, Version 4.0 [ Time Frame: 3 week cycle; the expected time frame is 18 weeks (or 6 cycles) ] [ Designated as safety issue: Yes ]Dose-limiting toxicity (DLT) will be based on cycle 1 toxicities.
- Exploratory biomarker analysis [ Time Frame: Blood specimens will be collected prior to treatment, prior to Cycles 2-6. In addition, a blood specimen will be collected if the patient is removed from the study due to progression of disease. the expected time frame is 18 weeks (or 6 cycles) ] [ Designated as safety issue: No ]Molecular markers predictive for response to panobinostat remain unknown. This trial offers the opportunity to retrospectively study biomarkers and their association with clinical outcomes.
- Efficacy of oral panobinostat in combination with cisplatin/pemetrexed in an expanded cohort of patients with NSCLC [ Time Frame: CT scans will be performed at baseline and every two cycles; the expected time frame is 18 weeks (or 6 cycles) ] [ Designated as safety issue: No ]Response rate will be assessed by CT scan. CT scans will be performed at baseline and every two cycles. The evaluation of response will be based on standard RECIST criteria.
|Study Start Date:||April 2011|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Phase I dose-escalation
Drug: panobinostat Drug: cisplatin Drug: pemetrexed Other: Biomarker studies
Drug: Panobinostat, Cisplatin, Pemetrexed
Drug: Panobinostat Oral (by mouth) once daily every Monday, Wednesday, and Friday for the first two weeks of each three week cycle (as per dose escalation schedule (dose levels 1 and 2: AUC 5; dose levels 3 and 4: AUC 6). Number of cycles: 6 maximum.
Drug: Cisplatin IV (in the vein) on day 1 of a 21-day cycle Number of cycles: 6 maximum. Drug: Pemetrexed IV (in the vein) on day 1 of a 21-day cycle Other: Correlative studies Biomarker Analysis: blood collected pre-study and Cycles 2-6, Day 1.
The purpose of this phase I study of oral panobinostat plus cisplatin and pemetrexed is to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) in patients with advanced solid tumors, with an emphasis in non-small cell lung cancer. Another purpose of this study is to find out if oral panobinostat in combination with cisplatin and pemetrexed can be administered safely without significant increase in toxicity and that the combination will increase efficacy compared to platinum-based doublet chemotherapy alone.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01336842
|United States, California|
|University of California Davis Cancer Center|
|Sacramento, California, United States, 95817|
|United States, Michigan|
|Henry Ford Health System|
|Detroit, Michigan, United States, 48202|
|Principal Investigator:||David Gandara, MD||University of California, Davis|