QOL-Stereotactic RadioSurgery, Temozolomide + Erlotinib-Rx of 1-3 Brain Metastases in NSCLC

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Treatment with radiosurgery, temozolomide, and erlotinib may affect brain function (the ability to think, learn, remember, and judge) in patients with non-small cell lung cancer and brain metastases. A study that evaluates brain function may help doctors plan the best treatment. PURPOSE: This phase II trial is studying the effect of radiosurgery, temozolomide, and erlotinib on brain function in patients with non-small cell lung cancer and brain metastases.

Detailed Description
-----------------
OBJECTIVES: Primary Determine the effect of stereotactic radiosurgery, temozolomide, and erlotinib hydrochloride on cognitive function in patients with non-small cell lung cancer and brain metastases. Secondary Determine the feasibility and safety of this regimen, in terms of tumor response, time to tumor progression in brain, survival, physical functioning, and quality of life, in these patients. Determine the frequency of O6-methylguanine-DNA methyltransferase promoter methylation in these patients. OUTLINE: This is a multicenter study. Patients undergo stereotactic radiosurgery on day -7. Patients receive oral temozolomide once daily on days 1-5 and oral erlotinib hydrochloride once daily on days 1-23. Treatment with temozolomide and erlotinib hydrochloride repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo cognitive function evaluation as measured by Mini-Mental Status Exam administration and scoring; quality of life assessment as measured by Functional Assessment of Cancer Therapy subscale; and physical functioning assessment as measured by Katz index of activities of daily living and Karnofsky performance status at baseline and then every 8 weeks during study treatment. Tumor tissue is examined by O6-methylguanine-DNA methyltransferase (MGMT gene) promotor methylation. After completion of study therapy, patients are followed every 3 months. PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.

Official Title
-----------------
Phase II Quality of Life Study of Stereotactic RadioSurgery, Temozolomide and Erlotinib Chemotherapy for the Treatment of 1-3 Brain Metastases in Non-small Cell Lung Cancer

Conditions
-----------------
Lung Cancer, Metastatic Cancer

Intervention / Treatment
-----------------
* Drug: erlotinib hydrochloride
* Drug: temozolomide
* Radiation: stereotactic radiosurgery


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed non-small cell lung cancer meeting the following criteria: One to 3 brain metastases, meeting the following criteria: No larger than 3 cm Greater than 5 mm from the optic apparatus Not involving the brainstem, pons, medulla, or midbrain Stable systemic disease for the past 3 months Less than 3 months since completion of primary treatment Measurable CNS disease as defined by RECIST criteria No leptomeningeal disease documented by MRI or cerebrospinal fluid cytologic evaluation PATIENT CHARACTERISTICS: Life expectancy ≥ 12 weeks Karnofsky performance status 60-100% Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 10 g/dL Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST ≤ 3.0 times ULN Serum creatinine ≤ 1.5 mg/dL Creatinine clearance > 50 mL/min No other malignancy within the past 5 years, except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix No concurrent major medical illness or psychiatric impairment that, in the investigator's opinion, would preclude study participation No concurrent active infections No known HIV positivity Not pregnant or nursing Negative pregnancy test Fertile patients must use effective nonhormonal contraception during and for 3 months after completion of study treatment PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior complete resection of all brain metastases No prior brain radiation therapy No prior temozolomide or erlotinib hydrochloride No concurrent enzyme-inducing anti-epileptic drugs No concurrent recombinant interleukin-11 No other concurrent anticancer investigational or commercial agents or therapies, including chemotherapy, immunotherapy, hormonal cancer therapy, radiation therapy, or cancer surgery No concurrent enrollment on another clinical trial Surgery for symptomatic brain lesions prior to radiosurgery allowed

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: erlotinib hydrochloride|Erlotinib will be administered orally on at a dose of 200 mg/day on Days 1-23 of each 28 day cycle.|
|Drug: temozolomide|Temozolomide will be administered orally at a dose of 150 mg/m2 on Days 1-5 for Cycle 1 then increased to 200 mg/m2 for Cycle 2 forward.|
|Radiation: stereotactic radiosurgery|Stereotactic radiosurgery will be performed prior to chemotherapy.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive function |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response |  | 2 years | 
| Time to tumor progression in brain |  | 2 years | 
| Survival |  | 2 years | 
| Quality of life as measured by FACT subscale |  | 2 years | 
| Physical functioning as measured by Karnofsky performance status and Katz index of activities of daily living |  | 2 years | 
| Frequency of O6-methylguanine-DNA methyltransferase promoter methylation |  | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
tumors metastatic to brain, stage IV non-small cell lung cancer