Maximum Tolerated Dose Study of Belinostat (PXD-101)in Combination With Paclitaxel Plus Carboplatin in Chemotherapy-Naive Patients With Stage IV Non-Small-Cell Lung Cancer (NSCLC)
|Stage IV Non-small Cell Lung Cancer||Drug: Belinostat, Carboplatin, Paclitaxel||Phase 1 Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||The Maximum Tolerated Dose and to Evaluate Safety and Efficacy of Belinostat (PXD-101) in Combination With Paclitaxel Plus Carboplatin in Chemotherapy-Naive Patients With Stage IV Non-Small-Cell Lung Cancer (NSCLC)|
- Maximum Tolerated Dose (MTD) [ Time Frame: 24 Months ]
- Safety [ Time Frame: 24 Months ]Safety will be mainly characterized by the number and severity of treatment emergent adverse events, and treatment related AEs that occur or worsen after the first dose of study treatment.
- Efficacy [ Time Frame: 24 Months ]Efficacy will be evaluated by measuring time to progression from first dose (PFS), and calculating the proportion of patients who achieve either CR or PR (ORR) using RECIST criteria.
- Tolerability [ Time Frame: 24 Months ]Tolerability will be mainly characterized by the number and severity of treatment emergent adverse events, and treatment related AEs that occur or worsen after the first dose of study treatment.
|Study Start Date:||December 2010|
|Study Completion Date:||August 2015|
|Primary Completion Date:||August 2015 (Final data collection date for primary outcome measure)|
|Experimental: Single arm, open label||
Drug: Belinostat, Carboplatin, Paclitaxel
Up to 6 cycles of combination therapy of belinostat plus carboplatin (AUC 6) and paclitaxel 200 mg/m2. Initial dose of belinostat will be 1000mg/m2 for MTD dose escalation evaluation.
Other Name: PXD-101
This is a Phase 1/2, multi-center, open label single arm study. Patients meeting all inclusion and exclusion criteria will receive up to 6 cycles of combination therapy of belinostat plus carboplatin (AUC 6) and paclitaxel 200 mg/m2.
During phase I the Maximum Tolerated Dose (MTD) of belinostat in combination with carboplatin and paclitaxel will be determined in patients with Stage IV non-small cell lung cancer who have received no prior systemic chemotherapy. The dose escalation study will be conducted using traditional escalation rule of 3+3 design, during the first cycle of therapy. Belinostat will be assessed at a starting dose level of 1000 mg/m2 and multiple dose levels may be evaluated. Doses of belinostat, carboplatin and paclitaxel will remain constant throughout the study, unless dose modification is required by toxicity. Treatment is given on days 1-5 of every 21-day cycle. Routine safety evaluations will be conducted on days, 1, 8, and 15 of every cycle. Tumor measurement will be done after every 2 cycles of the treatment.
Additional 20 patients will be treated at the MTD defined dose during phase II expansion portion of the study.
All patients will receive up to 6 cycles of combination therapy and be followed until occurrence of unacceptable toxicity, disease progression, withdrawal of consent or death.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01310244
|United States, Alabama|
|Clearview Cancer Institute (CCI)|
|Huntsville, Alabama, United States, 35805|
|United States, California|
|Sarcoma Oncology Center|
|Santa Monica, California, United States, 90403|
|United States, Florida|
|University Cancer Insitute|
|Boynton Beach, Florida, United States, 33426|
|United States, Missouri|
|Washington University School of Medicine|
|St. Louis, Missouri, United States, 63110|
|Principal Investigator:||Brian Matthews, MD||Clearview Cancer Institute|
|Principal Investigator:||Sant Chawla, MD||Sarcoma Oncology Center|
|Principal Investigator:||Saiama Waqar, MD||Washington University School of Medicine|
|Principal Investigator:||Thomas Neiderman, MD||University Cancer Insitute|