Radiation Therapy in Preventing Central Nervous System (CNS) Metastases in Patients With Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known if giving radiation therapy to the head is effective in preventing CNS metastases in patients who have stage III non-small cell lung cancer. PURPOSE: This randomized phase III trial is studying how well radiation therapy to the head works in preventing CNS metastases in patients who have been previously treated for stage III non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Determine whether prophylactic cranial irradiation improves survival after effective locoregional/systemic therapy in patients with stage IIIA or IIIB non-small cell lung cancer. Determine the neuropsychologic impact of this therapy in these patients. Assess quality of life of patients receiving this therapy. Determine the impact of this therapy on the incidence of CNS metastases in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease stage (IIIA vs IIIB), histology (non-squamous cell vs squamous cell), and prior surgery (yes vs no). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients undergo prophylactic cranial irradiation 5 days a week for 3 weeks. Arm II: Patients undergo observation. Patients are followed 3 months during the first year, every 6 months for 2-3 years and then annually thereafter. Quality of life is assessed at baseline and at months 6, 12, 24, 36, and 48. PROJECTED ACCRUAL: A total of 1,058 patients (529 per treatment arm) will be accrued for this study within 36 months.

Official Title
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A Phase III Comparison Of Prophylactic Cranial Irradiation (PCI) Versus Observation In Patients With Locally Advanced Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Radiation: Radiation therapy
* Other: Observation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of stage IIIA or IIIB non-small cell lung cancer Complete response, partial response, or stable disease after definitive locoregional therapy (with surgery and/or radiation therapy, with or without chemotherapy (chemotherapy alone does not constitute definitive therapy)) No more than 16 weeks since prior therapy No progressive disease No extracranial distant metastatic disease No suspicion of CNS metastases by MRI or CT scan PATIENT CHARACTERISTICS: Age 18 and over Performance status Not specified Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified Other No other malignancy within the past 3 years except nonmelanoma skin cancer Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent anticancer biologic therapy Chemotherapy See Disease Characteristics No concurrent anticancer cytotoxic chemotherapy Endocrine therapy Not specified Radiotherapy See Disease Characteristics No prior cranial irradiation Surgery See Disease Characteristics Other Recovered from all prior therapies No concurrent enrollment on any other phase III study that has progression-free, disease-free, or overall survival as an endpoint

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 |
| --- | --- |
| Experimental: Prophylactic cranial irradiation (PCI)<br>Radiation therapy | Radiation: Radiation therapy<br>* PCI is given to the whole brain in a dose of 2 Gy per fraction, 5 days per week, for 3 weeks for a total dose of 30 Gy.<br>|
| Other: Observation<br>Observation | Other: Observation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. This analysis was planned to occur when all patients had been potentially followed for at least 12 months. | From randomization to last follow-up. Analysis occurred after all patients had been on study for at least 12 months. Maximum follow-up at time of analysis was 96 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Deterioration in the Hopkins Verbal Learning Test - Revised (HVLT-R) Recall Score at One Year | The HVLT-R assesses verbal learning and memory. It incorporates 6 different forms to mitigate practice effects of repeated administrations. Each form includes 12 nouns (targets) with 4 words drawn from 3 semantic categories, which differ across the 6 forms. The recall part of the test involves memorizing a list of 12 targets for 3 consecutive trials for immediate recall. The raw score is derived by summing the number of targets correctly recalled and ranges from 0 to 36 with a higher score indicating better functioning. A patient was classified with deterioration if there was a statistically significant decrease in score from baseline to one year as determined by the method of reliable change index. | Baseline and one year post study entry | 
| Percentage of Subjects With Deterioration in the Hopkins Verbal Learning Test - Revised (HVLT-R) Delayed Recall Score at One Year | The HVLT-R assesses verbal learning and memory. It incorporates 6 different forms to mitigate practice effects of repeated administrations. Each form includes 12 nouns (targets) with 4 words drawn from 3 semantic categories, which differ across the 6 forms. The delayed recall part of the test involves memorizing a list of 12 targets and recalling them after a 20-minute delay. The raw score is derived by summing the number of targets correctly recalled and ranges from 0 to 12 with a higher score indicating better functioning. A patient was classified with deterioration if there was a statistically significant decrease in score from baseline to one year as determined by the method of reliable change index. | Baseline and one year post study entry | 
| Percentage of Subjects With Deterioration in Global Health Status From the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) at One Year | The EORTC QLQ is an integrated system for assessing the health-related quality of life (QOL) of cancer patients participating in international clinical trials. The QLQ Core-30 (QLQ-C30 ) is a 30-item self-report questionnaire that has patients rate the items on a 4-point scale, with 1 not at all to 4 very much and is composed of both multi-item scales and single-item measures, including 5 functional scales (physical, role, emotional, cognitive, social), 3 symptom scales (fatigue, nausea and vomiting, pain), a global health status, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties). The raw score is calculated as the mean of component items. This score is then standardized such that all of the scales and single-item measures range in score from 0-100. A high score for the global health status represents a high QOL. An increase from baseline to one year by >= 10 points was considered deterioration. | Baseline and one year from randomization | 
| Percentage of Subjects With Deterioration in Cognitive Functioning From the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) at One Year | The EORTC QLQ is an integrated system for assessing the health-related quality of life (QOL) of cancer patients participating in international clinical trials. The QLQ Core-30 (QLQ-C30 ) is a 30-item self-report questionnaire that has patients rate the items on a 4-point scale, with 1 not at all to 4 very much and is composed of both multi-item scales and single-item measures, including 5 functional scales (physical, role, emotional, cognitive, social), 3 symptom scales (fatigue, nausea and vomiting, pain), a global health status, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties). The raw score is calculated as the mean of component items. This score is then standardized such that all of the scales and single-item measures range in score from 0-100. A high score for a functional status represents a high QOL. An increase from baseline to one year by >= 10 points was considered deterioration. | Baseline and one year from randomization | 
| Percentage of Subjects With Deterioration in Fatigue From the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) at One Year | The EORTC QLQ is an integrated system for assessing the health-related quality of life (QOL) of cancer patients participating in international clinical trials. The QLQ Core-30 (QLQ-C30 ) is a 30-item self-report questionnaire that has patients rate the items on a 4-point scale, with 1 not at all to 4 very much and is composed of both multi-item scales and single-item measures, including 5 functional scales (physical, role, emotional, cognitive, social), 3 symptom scales (fatigue, nausea and vomiting, pain), a global health status, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties). The raw score is calculated as the mean of component items. This score is then standardized such that all of the scales and single-item measures range in score from 0-100. A high score for a symptom scale/item represents a high level of symptomatology/problems. An increase from baseline to one year by >= 10 points was considered deterioration. | Baseline and one year from randomization | 
| Percentage of Subjects With Deterioration in Future Uncertainty From the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Brain-20 (EORTC QLQ-B20) at One Year | The EORTC QLQ-B20 is a 20-item self-report that assesses 11 symptom scales/items such as future uncertainty, visual disorder, motor dysfunction, and communication deficit. Items are presented as questions on a scale ranging from 1 = not at all to 4 = very much. It is meant for use among brain cancer patients varying in disease stage and treatment modality (i.e. surgery, chemotherapy, radiotherapy, etc.) and should always be complemented by the QLQ-C30. The raw score is calculated as the mean of component items. This score is then standardized such that all of the scales and single-item measures range in score from 0 to 100. A high score for a symptom scale/item represents a high level of symptomatology/problems. An increase from baseline to one year by >= 10 points was considered deterioration. | Baseline and one year from randomization | 
| Percentage of Subjects With Deterioration in Communications Deficit From the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Brain-20 (EORTC QLQ-B20) at One Year | The EORTC QLQ-B20 is a 20-item self-report that assesses 11 symptom scales/items such as future uncertainty, visual disorder, motor dysfunction, and communication deficit. Items are presented as questions on a scale ranging from 1 = not at all to 4 = very much. It is meant for use among brain cancer patients varying in disease stage and treatment modality (i.e. surgery, chemotherapy, radiotherapy, etc.) and should always be complemented by the QLQ-C30. The raw score is calculated as the mean of component items. This score is then standardized such that all of the scales and single-item measures range in score from 0 to 100. A high score for a symptom scale/item represents a high level of symptomatology/problems. An increase from baseline to one year by >= 10 points was considered deterioration. | Baseline and one year from randomization | 
| Number of Subjects With Central Nervous System (CNS) Metastases in the First Year | The presence of metastases were determined by computerized tomography (CT) of the brain with and without contrast or by magnetic resonance imaging (MRI) of the brain with and without gadolinium, using the same method that was done prior to study entry. | From randomization to one year (Scans given at 6 and 12 months and additionally at other times within the time frame if clinically indicated.) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer