Everolimus and Whole-Brain Radiation Therapy in Treating Patients With Brain Metastasis From Non-Small Cell Lung Cancer
RATIONALE: Everolimus 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving everolimus together with whole-brain radiation therapy may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus and to see how well it works when given together with whole-brain radiation therapy in treating patients with brain metastasis from non-small cell lung cancer.
Radiation: whole-brain radiation therapy
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of RAD001 and Radiation Therapy in Patients With Brain Metastasis From Non-small Cell Lung Cancer (NSCLC)|
- Maximum tolerated dose [ Time Frame: 4 week DLT period ] [ Designated as safety issue: Yes ]Safety is measured by the rate of ≥ grade 3 hematological and non-hematologic study-related toxicities.
- Median survival (phase II) [ Time Frame: Off-study date. ] [ Designated as safety issue: No ]
- Intracranial response rate (phase II) [ Time Frame: Off-treatment date. ] [ Designated as safety issue: No ]
- Time to CNS (neurologic) progression (phase II) [ Time Frame: Off-treatment date. ] [ Designated as safety issue: No ]
- Time to systemic non-CNS progression (phase II) [ Time Frame: Off-treatment date ] [ Designated as safety issue: No ]
|Study Start Date:||May 2009|
|Study Completion Date:||February 2011|
|Primary Completion Date:||February 2011 (Final data collection date for primary outcome measure)|
RAD001 + radiation therapy
Taken by mouth once a day, for 15 days, one day prior to initiation of whole brain radiation therapy at 5 or 10 mg/day during the phase I component. One of these doses will be selected as the maximum tolerable dose and will be selected for the phase II componentRadiation: whole-brain radiation therapy
Standard whole brain radiation therapy (WBRT) 30 Gy will be given in ten fractions.
Phase I is intended to determine the maximum tolerated dose. Study drug will be administered orally, once a day, for 15 days, one day prior to initiation of WBRT at 5 or 10 mg/day during the phase I component. One of these doses will be selected as the maximum tolerable dose and will be selected for the phase II component.
- To determine the maximum-tolerated dose of everolimus when combined concurrently with whole-brain radiotherapy in patients with brain metastasis from stage IV non-small cell lung cancer. (Phase I)
- To evaluate the median survival of these patients treated with this regimen. (Phase II)
- To assess the response rates in these patients. (Phase II)
- To assess the safety and tolerability of this regimen in these patients. (Phase II)
- To determine time to CNS (neurological) progression, confirmed by MRI, in these patients. (Phase II)
- To determine time to systemic (non-CNS) progression in these patients. (Phase II)
OUTLINE: This is a multicenter, dose-escalation study of everolimus.
Patients undergo 10 fractions of whole-brain radiotherapy (WBRT) beginning on day 0, 5 days per week, and receive oral everolimus once daily on days -1 to 13. Beginning 2 weeks after completion of WBRT, patients receive oral everolimus once daily for 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 2 months for 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00892801
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232-6838|
|Vanderbilt-Ingram Cancer Center - Cool Springs|
|Nashville, Tennessee, United States, 37064|
|Principal Investigator:||Vicki Keedy, MD||Vanderbilt-Ingram Cancer Center|