Vorinostat, Paclitaxel, and Radiation Therapy in Treating Patients Unable to Tolerate Cisplatin With Stage III Non-Small Lung Cancer That Cannot Be Removed By Surgery
|Stage IIIA Non-small Cell Lung Cancer Stage IIIB Non-small Cell Lung Cancer||Drug: vorinostat Drug: paclitaxel Radiation: radiation therapy||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase I/II Clinical Trial Evaluating the Use of Vorinostat Combined With Paclitaxel and Radiotherapy in Patients With Inoperable Stage III Non-Small Cell Lung Cancer Unable to Tolerate Cisplatin|
- MTD of Vorinostat When Administered in Combination With Paclitaxel and Radiotherapy Therapy as Assessed by NCI Common Toxicity Criteria for Adverse Events (CTCAE) Version 3.0 (Phase I) [ Time Frame: 8 weeks ]Defined as the highest dose level at which no more than 1 of 6 patients experiences dose-limiting toxicity (DLT). Toxicity was graded according to the National Institutes of Health Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. A DLT was defined as any Grade 3 or higher non-hematologic adverse event with the exception of alopecia, fatigue, or anorexia. Nausea and/or vomiting that persisted > 48 hours despite optimal medical management at grade 3 or higher was considered a DLT. Hematologic dose-limiting toxicity was defined as either: Grade 4 neutropenia lasting for ≥ 7 days in duration, Grade > 3 febrile neutropenia with/without infection, Grade 4 thrombocytopenia or Grade 5 hematologic toxicity.
- Radiological Response Rate as Assessed by CT [ Time Frame: 12 weeks post-treatment, then every 3 months for 2 years, and then every 6 months for a year thereafter ]Count of participants with stable disease or partial response. Patients were evaluated for treatment response per RECIST criteria (version 1.0).
- Duration of Response [ Time Frame: Up to 3 years ]
- Progression-free Survival [ Time Frame: 1 year ]Kaplan-Meier estimate. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0).
- Overall Survival [ Time Frame: 1 year ]Kaplan-Meier estimate
- Safety and Toxicity of Vorinostat at the MTD as Assessed by NCI CTCAE Version 3.0 [ Time Frame: Weekly during treatment, 30 days post-treatment, and 12 weeks post-treatment ]Count of participants with a grade 3 or higher toxicity. Toxicities were assessed using the NCI CTCAE (v3.0). Grade 3 or higher toxicities were considered worse.
|Study Start Date:||March 2008|
|Study Completion Date:||September 2011|
|Primary Completion Date:||January 2010 (Final data collection date for primary outcome measure)|
Experimental: Treatment (vorinostat with paclitaxel and radiotherapy)
Patients receive vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
Other Names:Drug: paclitaxel
Other Names:Radiation: radiation therapy
Undergo radiation therapy
I. To determine the maximum tolerated dose (MTD) of vorinostat when administered in combination with paclitaxel and thoracic radiation therapy in patients with locally advanced NSCLC.
I. To assess the safety and toxicity of vorinostat when administered in combination with paclitaxel and thoracic radiation therapy in patients with locally advanced NSCLC.
II. To determine the radiological response rate, by computed tomography (CT) scan, of vorinostat when administered in combination with paclitaxel and thoracic radiation therapy in patients with locally advanced NSCLC.
III. To describe the progression free survival (PFS) and overall survival (OS) of this regiment over 3 years of follow up.
OUTLINE: This is a phase I, dose-escalation study of vorinostat followed by a phase II study.
Patients receive vorinostat orally (PO) once daily (QD), 5 days a week and paclitaxel intravenously (IV) over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, 12 weeks, every 3 months for 2 years, and then every 6 months for 1 year.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00662311
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Shilpen Patel||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|