Safety and Efficacy of Belinostat When Used With Standard of Care Chemotherapy for Untreated Non-small Cell Lung Cancer (HCH003)
|Non-Small-Cell Lung Carcinoma||Drug: Belinostat, carboplatin, paclitaxel and bevacizumab||Phase 1 Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|Official Title:||Phase Ib/II Study to Determine the Recommended Dose, Safety, and Preliminary Efficacy of Belinostat When Used in Combination With Carboplatin, Paclitaxel, and Bevacizumab in Patients With Untreated Non-small Cell Lung Cancer.|
- The recommended phase II dose of Belinostat when used in combination with carboplatin, paclitaxel and bevacizumab. [ Time Frame: 1 year ]The aim of the initial phase Ib component is to establish the maximum tolerated dose (MTD) of Belinostat when used with a standard of care carboplatin, paclitaxel and bevacizumab course of therapy ("BelCap-B") regimen. The MTD will be determined through the process of dose-limiting-toxicity evaluation.
- To evaluate overall survival with this investigational treatment. [ Time Frame: 2 years ]The percentage of participants who are alive at 2 years post initiation of investigational treatment.
- Long-term safety (late-effects up to 2 years) [ Time Frame: 2 years ]Long-term (up to 2 years) safety evaluation of the investigational treatment will be evaluated by ongoing evaluation of adverse events/late-effects using the NCI Common Toxicity Criteria.
- Evaluate disease response of participants who receive this investigational medication regimen [ Time Frame: 2 years ]Response to therapy will be measured by the RECIST criteria. The investigators will assess the percentage of research participants whose disease status indicates a response to investigational treatment according to the RECIST criteria.
- To evaluate progression-free survival [ Time Frame: 2 years ]The number (%) of participants who do not show evidence of disease progression (according to RECIST criteria)at 2 years post initial administration of the investigational product.
|Study Start Date:||April 2010|
|Study Completion Date:||February 2012|
|Primary Completion Date:||February 2012 (Final data collection date for primary outcome measure)|
This is a one arm, open label study of the investigational medication Belinostat.
Drug: Belinostat, carboplatin, paclitaxel and bevacizumab
Induction therapy will include 6 cycles of 5-days of medication administration followed by a 16 day rest period. Belinostat will be given once a day for 5 days total. Three dose levels will be evaluated (600mg/kg, 800 mg/kg, and 1000 mg/kg). In addition, participants will receive fixed doses of intravenous carboplatin (AUC 6), Paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg) once on day 3 of each cycle. Serial disease status evaluations will be done throughout the study.
In the absence of significant toxicity or disease progression, participants may continue with a maintenance regimen of bevacizumab and Belinostat for an additional 6 cycles. The dose of Belinostat received during maintenance will be that tolerated in the initial 6 cycles.
This is a Phase Ib/II, single center, open label, dose-finding study to evaluate the use of Belinostat when given with standard of care chemotherapy in patients with untreated, non-small cell lung cancer (NSCLC). In the Phase Ib portion, dose limiting toxicity evaluation will be used to determine the maximum tolerated dose (MTD) of Belinostat when given with fixed doses of bevacizumab, carboplatin, and paclitaxel(a BelCap-B regimen). Three dose levels of Belinostat are proposed (600mg/kg, 800mg/kg, 1000mg/kg). Determination of MTD will be the basis for establishing set dosing for the phase II component of the study.
The phase II portion of the study includes further drug safety evaluation and a preliminary assessment of efficacy of Belinostat when used with specified induction and maintenance regimens. Response will be evaluated through the RECIST criteria. Additional analysis will be done to estimate the time to response, progression free survival, median survival, and overall survival (OS) in study participants to 2 years post-initiation of cycle 1.
Based on a standard 3 x 3 statistical design, the phase Ib portion may accrue between 3 to 12 participants. Phase II will have a minimum sample size of 10 and a maximum of 16 patients. Participants who complete the Phase I portion and are able to advance to Phase II, will be evaluable for the Phase II objectives.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01090830
|United States, Florida|
|Holy Cross Hospital, Inc|
|Fort Lauderdale, Florida, United States, 33308|
|Principal Investigator:||Martin E Guiterrez, MD||Holy Cross Hospital|