Radiation Therapy Combined With Either Gefitinib or Temozolomide in Pats With NSCLC and Brain Metastases

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with either gefitinib or temozolomide may kill more tumor cells. PURPOSE: This randomized phase II trial is studying how well giving radiation therapy together with either gefitinib or temozolomide works in treating patients with non-small cell lung cancer and brain metastases.

Detailed Description
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OBJECTIVES: Primary Compare the efficacy of whole-brain radiotherapy combined with either gefitinib or temozolomide, in terms of overall survival, in patients with non-small cell lung cancer and brain metastases. Secondary Compare the tolerability and toxicity of these regimens in these patients. Compare the time to neurological disease progression, time to extracranial disease progression, and time to overall disease progression, in patients treated with these regimens. Compare adverse events in patients treated with these regimens. Compare cognitive function and quality of life of patients treated with these regimens. OUTLINE: This is a randomized, open-label, parallel-group, multicenter study. Patients are stratified according to extracranial disease (yes vs no), number of brain metastases (1-3 vs ≥ 4), prior chemotherapy (yes vs no), WHO performance status (0-1 vs 2), and participating center. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients undergo whole-brain radiotherapy (WBRT) once daily on days 1-5 and 8-12 and receive oral gefitinib once daily on days 1-28. Gefitinib treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Arm II: Patients undergo WBRT as in arm I and receive oral temozolomide once daily on days 1-21. Temozolomide treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline and on day 1 of courses 2, 3, and 5. After completion of study therapy, patients are followed every 3 months. PROJECTED ACCRUAL: A total of 30-86 patients (15-43 per treatment arm) will be accrued for this study within 3 years.

Official Title
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Whole Brain Radiotherapy in Combination With Gefitinib (Iressa) or Temozolomide (Temodal) for Brain Metastases From Non-Small Lung Cancer (NSCLC) A Randomized Phase II Trial

Conditions
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Lung Cancer, Metastatic Cancer

Intervention / Treatment
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* Drug: gefitinib
* Drug: temozolomide
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer AND newly diagnosed brain metastases meeting 1 of the following criteria: Multiple brain metastases Single brain metastasis not amenable to potentially curative treatment No advanced extracranial disease severely compromising vital functions and performance PATIENT CHARACTERISTICS: Age 18 and over Performance status WHO 0-2 Life expectancy Not specified Hematopoietic Hemoglobin > 10 g/dL Absolute neutrophil count > 1,500/mm^3 Platelet count > 100,000/mm^3 Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST and ALT ≤ 2.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN in the presence of documented bone metastases) No unstable or uncompensated hepatic disease that would preclude study participation Renal Creatinine clearance ≥ 40 mL/min No unstable or uncompensated renal disease that would preclude study participation Cardiovascular No myocardial infarction within the past 3 months No unstable or uncompensated cardiac disease that would preclude study participation Pulmonary No clinically active interstitial lung disease Patients with chronic stable radiographic changes who are asymptomatic eligible No other unstable or uncompensated respiratory disease that would preclude study participation Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 12 months after completion of study treatment No nausea, vomiting, inability to swallow whole tablets/capsules, or malabsorption syndrome that would preclude oral medication ingestion or absorption No psychiatric disorder that would preclude giving informed consent or study compliance No active infection No uncontrolled diabetes mellitus No other medical condition that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior temozolomide Endocrine therapy Concurrent corticosteroids allowed provided dose has been stable or decreasing for ≥ 4 days before study entry Radiotherapy No prior brain irradiation Surgery Not specified Other No prior gefitinib or erlotinib More than 30 days since prior investigational clinical trial participation No other concurrent experimental drugs No other concurrent anticancer therapy No concurrent treatment with any of the following: Phenytoin Carbamazepine Rifampin Barbiturates Hypericum perforatum (St. John's wort) Other enzyme-inducing anti-epileptic drugs or tuberculostatic treatments Any drug that contraindicates administration with study drugs

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I<br>Patients undergo whole-brain radiotherapy (WBRT) once daily on days 1-5 and 8-12 and receive oral gefitinib once daily on days 1-28. Gefitinib treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity | Drug: gefitinib<br>* Once daily during days 1-28<br>Radiation: radiation therapy<br>* Whole brain radiotherapy<br>|
| Active Comparator: Arm II<br>Patients undergo WBRT as in arm I and receive oral temozolomide once daily on days 1-21. Temozolomide treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity | Drug: temozolomide<br>* Once daily on days 1-21<br>Radiation: radiation therapy<br>* Whole brain radiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | life-long | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression |  | 28 days | 
| Time to neurological progression |  | 28 days | 
| Time to extracranial disease progression |  | 28 days | 
| Adverse events as measured at completion of study treatment |  | 28 days | 

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