Lung Cancer, Metastatic Cancer
Conditions
Keywords
tumors metastatic to brain, stage IV non-small cell lung cancer
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.
Interventions
DRUGerlotinib hydrochloride
Erlotinib will be administered orally on at a dose of 200 mg/day on Days 1-23 of each 28 day cycle.
DRUGtemozolomide
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.
RADIATIONstereotactic radiosurgery
Stereotactic radiosurgery will be performed prior to chemotherapy.
Sponsors
National Cancer Institute (NCI)
Schering-Plough
Genentech, Inc.
University of Medicine and Dentistry of New Jersey
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cognitive function | 2 years |
Secondary
| Measure | Time frame |
|---|---|
| Time to tumor progression in brain | 2 years |
| Survival | 2 years |
| Tumor response | 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 |
| Quality of life as measured by FACT subscale | 2 years |
Outcome results
None listed