Stereotactic Radiosurgery and Erlotinib in Treating Patients With Non-Small Cell Lung Cancer and Brain Metastases
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Stereotactic radiosurgery may be able to deliver x-rays directly to the tumor and cause less damage to normal tissue. Erlotinib may make tumor cells more sensitive to radiation therapy. Giving erlotinib together with stereotactic radiosurgery may kill more tumor cells.
PURPOSE: This phase I clinical trial is studying the side effects of erlotinib when given together with stereotactic radiosurgery and to see how well it works in treating patients with non-small cell lung cancer with brain metastases.
Drug: erlotinib hydrochloride
Other: immunoenzyme technique
Other: laboratory biomarker analysis
Other: liquid chromatography
Other: mass spectrometry
Other: pharmacological study
Radiation: stereotactic radiosurgery
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Open-Label, Dose-Finding Study to Evaluate the Safety and Efficacy of Concurrent Radiosurgery and Erlotinib Administration in Non-Small Cell Lung Cancer Patients With Brain Metastases|
- Acute and long-term toxicity (i.e., neurotoxicity, gastrointestinal, cutaneous, and hematologic) as assessed by NCI CTCAE v3.0. [ Designated as safety issue: Yes ]
- Disease progression [ Designated as safety issue: No ]
- Response rate of radiosurgically treated lesions in patients receiving concurrent erlotinib hydrochloride and radiosurgery on this study vs the response rate of historical controls previously treated with gamma knife radiosurgery alone [ Designated as safety issue: No ]
- CNS progression at 1 year [ Designated as safety issue: No ]
- Distribution of erlotinib hydrochloride in plasma and cerebrospinal fluid (CSF) [ Designated as safety issue: No ]
- CSF and serum biomarkers [ Designated as safety issue: No ]
- Incidence of subclinical leptomeningeal disease [ Designated as safety issue: No ]
|Study Start Date:||January 2009|
|Study Completion Date:||July 2009|
|Primary Completion Date:||July 2009 (Final data collection date for primary outcome measure)|
- To determine the acute as well as long-term toxicity (especially grade III neurotoxicity) of concurrent erlotinib hydrochloride and single-fraction radiosurgery in patients with non-small cell lung cancer (NSCLC) and brain metastases.
- To determine the freedom from progression in all detected lesions (i.e., radiosurgically treated and untreated) and the rate of response of radiosurgically treated lesions in patients receiving concurrent erlotinib hydrochloride and radiosurgery as compared with historical controls treated with gamma knife radiosurgery alone at UCSF.
- To measure the rate of freedom from any CNS progression in these patients at 1 year post treatment.
- To assess cerebrospinal fluid (CSF) distribution of erlotinib hydrochloride by measuring both erlotinib hydrochloride and its major metabolite, OSI-420, in plasma and CSF at 4 or more days after initial erlotinib hydrochloride administration but before radiosurgery, and again at 4 weeks after stereotactic radiosurgery (optional).
- To perform CSF and serum biomarker analysis for NSCLC using 2-dimensional liquid chromatography or mass spectrometry (2D-LC/MS).
- To determine the incidence of subclinical leptomeningeal disease in patients assigned to gamma-knife treatment and who do not exhibit signs or symptoms or carcinomatous meningitis.
OUTLINE: Patients receive oral erlotinib hydrochloride once daily for at least 7 days. Patients then undergo stereotactic radiosurgery on day 0. Beginning the day after radiosurgery, patients receive erlotinib hydrochloride once daily for 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients may continue to receive erlotinib hydrochloride at the discretion of their oncologist.
Patients undergo cerebrospinal fluid (CSF) and blood sample collection at baseline (at least 4 days after starting erlotinib hydrochloride and prior to radiosurgery) for pharmacokinetic and biomarker correlative studies. Samples are analyzed for concentrations of erlotinib hydrochloride by 2-dimensional-liquid chromatography/mass spectrometry and antithrombin by enzyme-linked immunosorbent assay.
After completion of study therapy, patients are followed every 3 months for 1 year.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00738335
|United States, California|
|UCSF Helen Diller Family Comprehensive Cancer Center|
|San Francisco, California, United States, 94115|
|Principal Investigator:||James L. Rubenstein, MD, PhD||University of California, San Francisco|