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

University of Medicine and Dentistry of New Jersey

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Conditions

Lung Cancer Metastatic Cancer

Interventions

erlotinib hydrochlorideDRUG

Erlotinib will be administered orally on at a dose of 200 mg/day on Days 1-23 of each 28 day cycle.

temozolomideDRUG

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.

stereotactic radiosurgeryRADIATION

Stereotactic radiosurgery will be performed prior to chemotherapy.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Cognitive function

Time frame: 2 years

Secondary Outcomes

Tumor response

Time frame: 2 years

Time to tumor progression in brain

Time frame: 2 years

Survival

Time frame: 2 years

Quality of life as measured by FACT subscale

Time frame: 2 years

Physical functioning as measured by Karnofsky performance status and Katz index of activities of daily living

Time frame: 2 years

Frequency of O6-methylguanine-DNA methyltransferase promoter methylation

Time frame: 2 years

Data from ClinicalTrials.gov

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