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

Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00048997
• Other study ID #: RTOG-0214
• Secondary ID: CDR0000257200ECO
• Status: Completed
• Phase: Phase 3
• Start date: September 2002
• Est. completion date: December 2016

Study information

• Verified date: May 2018
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 356
• Est. completion date: December 2016
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Radiation:
• Radiation therapy
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.

Other:
• Observation

Locations

Country	Name	City	State
United States	Cancer Institute of New Jersey at Cooper University Hospital - Camden	Camden	New Jersey
United States	Resurrection Medical Center	Chicago	Illinois
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Shore Regional Cancer Center at Memorial Hospital - Easton	Easton	Maryland
United States	MetroWest Medical Center - Framingham Union Hospital	Framingham	Massachusetts
United States	Central Maine Comprehensive Cancer Center at Central Maine Medical Center	Lewiston	Maine
United States	Arizona Oncology Services Foundation	Phoenix	Arizona
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah
United States	Maine Center for Cancer Medicine and Blood Disorders - Scarborough	Scarborough	Maine
United States	Virginia G. Piper Cancer Center at Scottsdale Healthcare - Osborn	Scottsdale	Arizona
United States	Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea	Scottsdale	Arizona
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	Eastern Cooperative Oncology Group, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (4)

Gondi V, Paulus R, Bruner D, et al.: Prognostic significance of QOL deterioration during early lung cancer survivorship: secondary analysis of RTOG 0212 and 0214. [Abstract] J Clin Oncol 29 (Suppl 15): A-6061, 2011.

Gore E. RTOG 0214: a phase III comparison of prophylactic cranial irradiation versus observation in patients with locally advanced non-small cell lung cancer. Clin Adv Hematol Oncol. 2005 Aug;3(8):625-6. — View Citation

Gore EM, Bae K, Wong SJ, Sun A, Bonner JA, Schild SE, Gaspar LE, Bogart JA, Werner-Wasik M, Choy H. Phase III comparison of prophylactic cranial irradiation versus observation in patients with locally advanced non-small-cell lung cancer: primary analysis — View Citation

Sun A, Bae K, Gore EM, Movsas B, Wong SJ, Meyers CA, Bonner JA, Schild SE, Gaspar LE, Bogart JA, Werner-Wasik M, Choy H. Phase III trial of prophylactic cranial irradiation compared with observation in patients with locally advanced non-small-cell lung ca — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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.)