Brain Irradiation in Treating Patients With Limited-Stage Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known which radiation therapy regimen is more effective in preventing brain metastases in patients with limited-stage small cell lung cancer while taking into account chronic neurotoxicity from radiation therapy. PURPOSE: This randomized phase II trial compares the incidence of chronic neurotoxicity between three different brain irradiation regimens. The corresponding phase III component addressing the prevention of brain metastases was run by EORTC and reported separately (NCT00005062).

Detailed Description
-----------------
OBJECTIVES: Compare the incidence of chronic neurotoxicity in patients treated with these regimens. Compare quality of life of patients treated with these regimens. (phase III closed to accrual as of 12/31/05) OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (60 and under vs over 60) and time since induction therapy (90 days or less vs 91-180 days vs 181-240 days). Patients are randomized to 1 of 3 treatment arms. Arm I: Patients undergo prophylactic cranial irradiation (PCI) once daily 5 days a week. Treatment continues for 2 weeks in the absence of unacceptable toxicity. Arm II: Patients undergo PCI once daily 5 days a week. Treatment continues for 2.6 weeks in the absence of unacceptable toxicity. Arm III: Patients undergo PCI twice daily 5 days a week. Treatment continues for 3.4 weeks in the absence of unacceptable toxicity. Quality of life is assessed at baseline, every 6 months for 1 year, and then annually for 3 years. Patients are followed every 6 months for 1 year and then annually for 3 years. PROJECTED ACCRUAL: A total of 264 patients will be accrued for this study within 3.5 years.

Official Title
-----------------
A Phase II Randomized Trial Of Two Dose Schedules For Delivering Prophylactic Cranial Irradiation For Patients With Limited Disease Small Cell Lung Cancer

Conditions
-----------------
Lung Cancer

Intervention / Treatment
-----------------
* Radiation: Prophylactic cranial irradiation, 2.5 Gy fx
* Radiation: Prophylactic cranial irradiation, 2.0 Gy fx
* Radiation: Prophylactic cranial irradiation, 1.5 Gy fx


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed small cell lung cancer by fine needle aspiration, biopsy, or 2 positive sputa Limited stage (I-IIIB) Confined to 1 hemithorax No T4 based on malignant pleural effusion, or N3 disease based on contralateral hilar or contralateral supraclavicular involvement Complete response after induction chemotherapy (with or without thoracic radiotherapy) Consolidative chest radiotherapy may be initiated before study No radiographic evidence of any of the following: Brain metastases Normal brain CT scan or MRI less than 1 month before study Ipsilateral lung metastases Malignant pleural effusion Minimal pleural effusion by chest CT scan allowed, but not by chest x-ray PATIENT CHARACTERISTICS: Age Not specified Performance status Zubrod 0-1 Life expectancy Not specified Hematopoietic Absolute granulocyte count at least 1,500/mm^3 Platelet count at least 75,000/mm^3 Hemoglobin at least 10.0 g/dL^ Hepatic Not specified Renal Not specified Pulmonary See Disease Characteristics Other Not pregnant or nursing Fertile patients must use effective contraception Neurological function class 1 or 2 No epilepsy requiring permanent oral medication No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix No other serious medical or psychiatric condition that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics At least 1 week since prior chemotherapy No concurrent chemotherapy Endocrine therapy Not specified Radiotherapy See Disease Characteristics No prior external beam radiotherapy to the head or neck, including stereotactic radiotherapy Concurrent thoracic radiotherapy allowed Surgery Not specified Other No concurrent antitumor agents

Ages Eligible for Study
-----------------
Maximum Age: 120 Years

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

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

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

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>Prophylactic cranial irradiation, 2.5 Gy fx | Radiation: Prophylactic cranial irradiation, 2.5 Gy fx<br>* Prophylactic cranial irradiation, 2.5 Gy once daily, M-F, in 10 fractions (fx) for a total of 25 Gy<br>* Other names: PCI;|
| Experimental: Arm II<br>Prophylactic cranial irradiation, 2.0 Gy fx | Radiation: Prophylactic cranial irradiation, 2.0 Gy fx<br>* Prophylactic cranial irradiation, 2.0 Gy once daily, M-F, in 18 fractions (fx) for a total of 36 Gy<br>* Other names: PCI;|
| Experimental: Arm III<br>Prophylactic cranial irradiation, 1.5 Gy fx | Radiation: Prophylactic cranial irradiation, 1.5 Gy fx<br>* Prophylactic cranial irradiation, 1.5 Gy twice daily, M-F, in 24 fractions (fx) for a total dose of 36 Gy<br>* Other names: PCI;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Chronic Neurotoxicity | Chronic neurotoxicity is defined as a drop in one standard error of measurement (SEM) in any one of the three tests comprising the neuropsychological test battery (Hopkins Verbal Learning Test, Controlled Word Association Test, and Trail-Making Test) without development of brain metastasis by one year. The SEM is calculated as the standard deviation of the baseline test multiplied by the square root of one minus the published reliability coefficient for the test. | From study registration to one year. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
limited stage small cell lung cancer