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Lung CancerPhase 3NCT00048997

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

A Phase 3 study testing Radiation therapy and Observation in people with Lung Cancer, run by Radiation Therapy Oncology Group at 14 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lung Cancer
What is being tested?
Radiation therapy and Observation
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
356 participants
Where
14 sitesUnited States
Study dates
Sep 2002to Dec 2016
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites
  • Cancer Institute of New Jersey at Cooper University Hospital - Camden

    Camden, New Jersey, 08103

  • Resurrection Medical Center

    Chicago, Illinois, 60631

  • Geisinger Cancer Institute at Geisinger Health

    Danville, Pennsylvania, 17822-0001

  • Josephine Ford Cancer Center at Henry Ford Hospital

    Detroit, Michigan, 48202

  • Shore Regional Cancer Center at Memorial Hospital - Easton

    Easton, Maryland, 21601

  • MetroWest Medical Center - Framingham Union Hospital

    Framingham, Massachusetts, 01702

  • Central Maine Comprehensive Cancer Center at Central Maine Medical Center

    Lewiston, Maine, 04240

  • Arizona Oncology Services Foundation

    Phoenix, Arizona, 85013

  • Huntsman Cancer Institute at University of Utah

    Salt Lake City, Utah, 84112

  • Maine Center for Cancer Medicine and Blood Disorders - Scarborough

    Scarborough, Maine, 04074

  • Virginia G. Piper Cancer Center at Scottsdale Healthcare - Osborn

    Scottsdale, Arizona, 85251

  • Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea

    Scottsdale, Arizona, 85260

  • Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center

    Wilkes-Barre, Pennsylvania, 18711

  • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital

    Yakima, Washington, 98902

Other trials in United States

About this study

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

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.

Read the 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.

Conditions
Lung Cancer
Being tested
Radiation therapy, Observation
Keywords
stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer
Medical subject headings
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Radiation therapyRadiation

    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.

  • ObservationOther

Study groups in NCT00048997
Study groupRoleWhat they receive
Prophylactic cranial irradiation (PCI)ExperimentalRadiation therapy
Receives: Radiation: Radiation therapy
ObservationOtherObservation
Receives: Other: Observation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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 (8)
  1. 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.

    Measured: Baseline and one year post study entry

  2. 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.

    Measured: Baseline and one year post study entry

  3. 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.

    Measured: Baseline and one year from randomization

  4. 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.

    Measured: Baseline and one year from randomization

  5. 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.

    Measured: Baseline and one year from randomization

  6. 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.

    Measured: Baseline and one year from randomization

  7. 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.

    Measured: Baseline and one year from randomization

  8. 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.

    Measured: From randomization to one year (Scans given at 6 and 12 months and additionally at other times within the time frame if clinically indicated.)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startSep 2002
  3. Primary completionDec 2008
  4. Study completionDec 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
356 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00048997
Sponsor's protocol ID
RTOG-0214
Other IDs
CDR0000257200, ECOG-RTOG-0214
Status last verified
May 2018
First submitted
12 Nov 2002
Last updated
8 Jun 2018
Data monitoring committee
Yes

Publications

  • 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 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.

    PubMed 21135270
  • 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.

    PubMed 21135267
  • 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.

    PubMed 16167048
  • 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.

    PubMed 30869743

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Radiation therapy and Observation in people with Lung Cancer, run by Radiation Therapy Oncology Group at 14 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Oct 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00048997, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2018; AzTrials last refreshed its copy on 7 Nov 2026.

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