Clinical trial NCT00048997: Radiation Therapy in Preventing Central Nervous System (CNS) Metastases in Patients With Non-Small Cell Lung Cancer
Official title: A Phase III Comparison Of Prophylactic Cranial Irradiation (PCI) Versus Observation In Patients With Locally Advanced Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Cancer
Keywords: stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: Eastern Cooperative Oncology Group
First posted: 2003-01-27
Enrollment: 356
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival
timeFrame: 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 outcomes:
measure: Percentage of Subjects With Deterioration in the Hopkins Verbal Learning Test - Revised (HVLT-R) Recall Score at One Year
timeFrame: Baseline and one year post study entry
measure: Percentage of Subjects With Deterioration in the Hopkins Verbal Learning Test - Revised (HVLT-R) Delayed Recall Score at One Year
timeFrame: Baseline and one year post study entry
measure: 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
timeFrame: Baseline and one year from randomization
measure: 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
timeFrame: Baseline and one year from randomization
measure: 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
timeFrame: Baseline and one year from randomization
measure: 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
timeFrame: Baseline and one year from randomization
measure: 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
timeFrame: Baseline and one year from randomization
measure: Number of Subjects With Central Nervous System (CNS) Metastases in the First Year
timeFrame: From randomization to one year (Scans given at 6 and 12 months and additionally at other times within the time frame if clinically indicated.)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Oncology Services Foundation
state: Arizona
city: Scottsdale
country: United States
facility: Virginia G. Piper Cancer Center at Scottsdale Healthcare - Osborn
state: Arizona
city: Scottsdale
country: United States
facility: Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea
state: Arizona
city: Chicago
country: United States
facility: Resurrection Medical Center
state: Illinois
city: Lewiston
country: United States
facility: Central Maine Comprehensive Cancer Center at Central Maine Medical Center
state: Maine
city: Scarborough
country: United States
facility: Maine Center for Cancer Medicine and Blood Disorders - Scarborough
state: Maine
city: Easton
country: United States
facility: Shore Regional Cancer Center at Memorial Hospital - Easton
state: Maryland
city: Framingham
country: United States
facility: MetroWest Medical Center - Framingham Union Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Hospital
state: Michigan
city: Camden
country: United States
facility: Cancer Institute of New Jersey at Cooper University Hospital - Camden
state: New Jersey
city: Danville
country: United States
facility: Geisinger Cancer Institute at Geisinger Health
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute at University of Utah
state: Utah
city: Yakima
country: United States
facility: North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
state: Washington
Study officials:
affiliation: Medical College of Wisconsin
name: Elizabeth M. Gore, MD
role: STUDY_CHAIR
affiliation: University of Alabama at Birmingham
name: James A. Bonner, MD
role: STUDY_CHAIR
References:
citation: 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.
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 of radiation therapy oncology group study RTOG 0214. J Clin Oncol. 2011 Jan 20;29(3):272-8. doi: 10.1200/JCO.2010.29.1609. Epub 2010 Dec 6.
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 cancer: neurocognitive and quality-of-life analysis. J Clin Oncol. 2011 Jan 20;29(3):279-86. doi: 10.1200/JCO.2010.29.6053. Epub 2010 Dec 6.
citation: 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. No abstract available.
citation: Sun A, Hu C, Wong SJ, Gore E, Videtic G, Dutta S, Suntharalingam M, Chen Y, Gaspar LE, Choy H. Prophylactic Cranial Irradiation vs Observation in Patients With Locally Advanced Non-Small Cell Lung Cancer: A Long-term Update of the NRG Oncology/RTOG 0214 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2019 Jun 1;5(6):847-855. doi: 10.1001/jamaoncol.2018.7220.