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
- 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
- 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
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.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Acute and long-term toxicity (i.e., neurotoxicity, gastrointestinal, cutaneous, and hematologic) as assessed by NCI CTCAE v3.0.
James L. Rubenstein, MD, PhD
University of California, San Francisco
United States: Food and Drug Administration
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|