Lung CancerPhase 2NCT00960999
Radiation Therapy in Treating Patients With Stage I Non-Small Cell Lung Cancer
A Phase 2 study testing Single-fraction stereotactic body radiation therapy (SBRT) and Multiple-fraction stereotactic body radiation therapy (SBRT) in people with Lung Cancer, run by Radiation Therapy Oncology Group at 38 sites in 2 countries.
Trial summary
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. 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?
- Single-fraction stereotactic body radiation therapy (SBRT) and Multiple-fraction stereotactic body radiation therapy (SBRT)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 94 participants
- Where
- 38 sitesin 2 countries
- Study dates
- Nov 2009to 14 May 2018
- Phase
- Phase 2
- 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
Who may be able to join
- Histological confirmation (by biopsy or cytology) of non-small cell lung cancer (NSCLC) prior to treatment; the following primary cancer types are eligible: squamous cell carcinoma, adenocarcinoma, large cell carcinoma, large cell neuroendocrine, or non-small cell carcinoma not otherwise specified; Note: although bronchioloalveolar cell carcinoma is a subtype of NSCLC, patients with the pure type of this malignancy are excluded from this study because the spread of this cancer between adjacent airways is difficult to target on computed tomography (CT).
- Stage T1, N0, M0 or T2 (≤ 5 cm), N0, M0, (AJCC Staging, 6th Ed.), based upon #3.
- Minimum diagnostic workup:
- History/physical examination, including weight and assessment of Zubrod performance status, within 4 weeks prior to registration;
- Evaluation by an experienced thoracic cancer clinician (a thoracic surgeon, medical oncologist, radiation oncologist, or pulmonologist) within 8 weeks prior to registration;
- CT scan with intravenous contrast (unless medically contraindicated) within 8 weeks prior to registration of the entirety of both lungs and the mediastinum, liver, and adrenal glands; the primary tumor dimension will be measured on the CT. Positron emission tomography (PET) evaluation of the liver and adrenal glands also is permitted. In addition, if the enrolling institution has a combined PET/CT scanner and both aspects are of diagnostic quality and read by a trained radiologist, the PET/CT will meet the staging requirements for both CT and PET.
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- Whole body or wide field FDG-PET within 8 weeks prior to registration with adequate visualization of the primary tumor and draining lymph node basins in the hilar and mediastinal regions and adrenal glands; in the event of lung consolidation, atelectasis, inflammation or other confounding features, PET-based imaging correlated with CT imaging will establish the maximal tumor dimensions. Standardized uptake value (SUV) must be measured on PET. To be included in this analysis, the patient's PET studies must be performed with a dedicated bismuth germanium oxide (BGO), lutetium oxyorthosilicate (LSO), or gadolinium oxyorthosilicate (GSO) PET or PET/CT scanner. PET scanners with sodium iodide (Nal) detectors are not acceptable. If the baseline PET study is performed at the treating institution (or its affiliated PET facility), it is recommended that the reassessment PET scans be performed at the same site.
- Pulmonary function tests (PFTs): Routine spirometry, lung volumes, and diffusion capacity, within 8 weeks prior to registration; arterial blood gases are optional. Note: All patients enrolled in this study must have these pulmonary assessments whether or not the reason for their medical inoperability is pulmonary based, since the objective assessment of pulmonary factors is a component of the outcomes assessment for this study.
- Patients with hilar or mediastinal lymph nodes ≤ 1cm and no abnormal hilar or mediastinal uptake on PET will be considered N0. Patients with > 1 cm hilar or mediastinal lymph nodes on CT or abnormal PET (including suspicious but non-diagnostic uptake) may still be eligible if directed tissue biopsy of all abnormally identified areas are negative for cancer.
- The patient's resectable NSCLC must be considered medically inoperable by an experienced thoracic cancer clinician (a thoracic surgeon, medical oncologist, radiation oncologist, or pulmonologist) or a standard lobectomy and mediastinal lymph node dissection/sampling procedure. The patient may have underlying physiological medical problems that would prohibit a surgery due to a low probability of tolerating general anesthesia, the operation, the postoperative recovery period, or the removal of adjacent functioning lung. These types of patients with severe underlying health problems are deemed "medically inoperable." Standard justification for deeming a patient medically inoperable based on pulmonary function for surgical resection of NSCLC may include any of the following:
- Baseline forced expiratory volume in one second (FEV1) < 40% predicted;
- Postoperative FEV1 < 30% predicted;
- Severely reduced diffusion capacity;
- Baseline hypoxemia and/or hypercapnia;
- Exercise oxygen consumption < 50% predicted;
- Severe pulmonary hypertension;
- Diabetes mellitus with severe end organ damage;
- Severe cerebral, cardiac, or peripheral vascular disease;
- Severe chronic heart disease. If the patient has resectable disease but declines surgery after consulting with a thoracic surgeon, he/she will be considered eligible.
- The patient must have measurable disease.
- Zubrod Performance Status 0-2;
- Age ≥ 18;
- Negative serum or urine pregnancy test within 72 hours prior to registration for women of childbearing potential;
- Women of childbearing potential and male participants must agree to use a medically effective means of birth control, such as condom/diaphragm and spermicidal foam, intrauterine device (IUD), or prescription birth control pills, throughout their participation in the treatment phase of the study
- The patient must provide study specific informed consent prior to study entry.
Who cannot join
- Patients with T2 primary tumors > 5 cm or involving the central plural and/or structures of the mediastinum;
- The primary tumor of any T-stage within or touching the zone of the proximal bronchial tree, defined as a volume 2 cm in all directions around the proximal bronchial tree (carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus, right and left lower lobe bronchi);
- Direct evidence of regional or distant metastases after appropriate staging studies, or synchronous primary malignancy or prior malignancy in the past 2 years except for invasive malignancy that has been treated definitively and the patient remains disease free for > 3 years with life expectancy of > 3 years or carcinoma in situ or early stage skin cancers that have been treated definitively;
- Previous radiotherapy to the lung or mediastinum;
- Previous chemotherapy for this lung or mediastinum tumor; chemotherapy for another invasive malignancy is permitted if it has been treated definitively and the patient has remained disease free for > 3 years.
- Previous surgery for this lung or mediastinum tumor;
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- Plans for the patient to receive other concomitant antineoplastic therapy (including standard fractionated radiotherapy, chemotherapy, biological therapy, vaccine therapy, and surgery) while on this protocol except at disease progression;
- Patients with active systemic, pulmonary, or pericardial infection;
- Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo or fetus.
Trial locations and contacts
38 sites in 2 countries.
38 sites in 2 countries
United States35 sites
INOVA Alexandria Hospital
Alexandria, Virginia, 22304
Auburn Radiation Oncology
Auburn, California, 95603
University of Colorado Cancer Center at UC Health Sciences Center
Aurora, Colorado, 80045
Alta Bates Summit Comprehensive Cancer Center
Berkeley, California, 94704
Roswell Park Cancer Institute
Buffalo, New York, 14263-0001
Radiation Oncology Centers - Cameron Park
Cameron Park, California, 95682
Mercy Cancer Center at Mercy San Juan Medical Center
Carmichael, California, 95608
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, 60611-3013
Case Comprehensive Cancer Center
Cleveland, Ohio, 44106-5065
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, 44195
Geisinger Cancer Institute at Geisinger Health
Danville, Pennsylvania, 17822-0001
Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, 48202
Dale and Frances Hughes Cancer Center at Pocono Medical Center
East Stroudsburg, Pennsylvania, 18301
Great Lakes Cancer Institute at McLaren Regional Medical Center
Flint, Michigan, 48532
Parkview Regional Cancer Center at Parkview Health
Fort Wayne, Indiana, 46805
Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033-0850
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, 77030-4009
Baptist Cancer Institute - Jacksonville
Jacksonville, Florida, 32207
CCOP - Kansas City
Kansas City, Missouri, 64131
Lucille P. Markey Cancer Center at University of Kentucky
Lexington, Kentucky, 40536-0093
James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky, 40202
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, 53226
Veterans Affairs Medical Center - Milwaukee
Milwaukee, Wisconsin, 53295
Community Cancer Center
Normal, Illinois, 61761
M.D. Anderson Cancer Center at Orlando
Orlando, Florida, 32806
Advocate Lutheran General Cancer Care Center
Park Ridge, Illinois, 60068-1174
OSF St. Francis Medical Center
Peoria, Illinois, 61637
Providence Cancer Center at Providence Portland Medical Center
Portland, Oregon, 97213-2967
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, 23298-0037
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, 14642
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115
Memorial Hospital of South Bend
South Bend, Indiana, 46601
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
St Louis, Missouri, 63110
Stony Brook University Cancer Center
Stony Brook, New York, 11794-9446
Flower Hospital Cancer Center
Sylvania, Ohio, 43560
Canada3 sites
Grand River Regional Cancer Centre at Grand River Hospital
Kitchener, Ontario, N2G 1G3
McGill Cancer Centre at McGill University
Montreal, Quebec, H2W 1S6
Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
About this study
Official title: A Randomized Phase II Study Comparing 2 Stereotactic Body Radiation Therapy (SBRT) Schedules for Medically Inoperable Patients With Stage I Peripheral Non-Small Cell Lung Cancer
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. It is not yet known which regimen of stereotactic body radiation therapy is more effective in treating patients with non-small cell lung cancer.
PURPOSE: This randomized phase II trial is studying the side effects of two radiation therapy regimens and to see how well they work in treating patients with stage I non-small cell lung cancer.
Read the detailed description
OBJECTIVES:
Primary
- To determine the 1-year rate of ≥ grade 3 adverse events that are definitely, probably, or possibly related to treatment with single fraction vs multiple fraction stereotactic body radiotherapy in medically inoperable patients with stage I peripheral non-small cell lung cancer.
Secondary
- To estimate the 1-year primary tumor control rate in these patients.
- To estimate the 1-year overall survival and disease-free survival rate of these patients.
- To assess FDG-PET (fluorodeoxyglucose - positron emission tomography) standardized uptake value changes as a measure of treatment response and outcomes.
- To determine pulmonary function changes by treatment arm and response.
- To determine the association between biomarkers and primary tumor control and/or ≥ grade 2 radiation pneumonitis.
OUTLINE: This is a multicenter study. Patients are stratified according to Zubrod performance status (0 vs 1 vs 2) and T stage (T1 vs T2). Patients are randomized to 1 of 2 treatment arms.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.
- Conditions
- Lung Cancer
- Being tested
- Single-fraction stereotactic body radiation therapy (SBRT), Multiple-fraction stereotactic body radiation therapy (SBRT)
- Keywords
- stage I non-small cell lung cancer, squamous cell lung cancer, adenocarcinoma of the lung, large cell lung cancer
- Medical subject headings
- Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Adenocarcinoma of Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Single-fraction stereotactic body radiation therapy (SBRT)Radiation
34 Gy in 1 fraction to the prescription line at the edge of the planning target volume (PTV). The maximum dose must exist within the PTV, and the prescription isodose surface must be ≥ 60% and < 90% of the maximum dose. 99% of the PTV must receive a minimum of 90% of the prescription dose. The maximum dose to any point ≥ 2 cm away from the PTV in any direction must be at least < 50% of the prescription dose. The percent of the lungs (excluding PTV) receiving 20 Gy or more must be < 10%.
Multiple-fraction stereotactic body radiation therapy (SBRT)Radiation
48 Gy in four 12 Gy fractions to the prescription line at the edge of the planning target volume (PTV). Treatments are given on 4 consecutive calendar days, but at least 18 hours apart. The maximum dose must exist within the PTV, and the prescription isodose surface must be ≥ 60% and < 90% of the maximum dose. 99% of the PTV must receive a minimum of 90% of the prescription dose. The maximum dose to any point ≥ 2 cm away from the PTV in any direction must be at least < 50% of the prescription dose. The percent of the lungs (excluding PTV) receiving 20 Gy or more must be < 10%.
| Study group | Role | What they receive |
|---|---|---|
| Single-fraction SBRT (34 Gy) | Experimental | Single-fraction stereotactic body radiation therapy (SBRT) of 34 Gy Receives: Radiation: Single-fraction stereotactic body radiation therapy (SBRT) |
| Multiple-fraction SBRT (48 Gy) | Experimental | Multiple-fraction stereotactic body radiation therapy (SBRT) given in four daily 12 Gy fractions for a total dose of 48 Gy Receives: Radiation: Multiple-fraction stereotactic body radiation therapy (SBRT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Counts of ≥ Grade 3 Adverse Events (AE) Graded by CTCAE v4 (Common Terminology Criteria for Adverse Events) That Are Definitely, Probably, or Possibly Related to Treatment (DPPRT)
Number of patients with ≥ grade 3 AE occurring within 1 year of treatment (TRT) start and reported as DPPRT among this subset of CTCAE v4: pericardial effusion, pericarditis, restrictive cardiomyopathy, dysphagia, esophagitis, esophageal fistula/obstruction/perforation/stenosis/ulcer/hemorrhage, rib fracture, brachial plexopathy, recurrent laryngeal nerve palsy, myelitis, atelectasis, bronchopulmonary/mediastinal/pleural/tracheal hemorrhage, bronchial/pulmonary/bronchopleural/tracheal fistula, hypoxia, bronchial/tracheal obstruction, pleural effusion, pneumonitis, pulmonary fibrosis, skin ulceration (thorax only), FEV1 (Forced Expiratory Volume) or FVC (forced vital capacity) decline, or grade 5 related to TRT. Each arm is considered independently. For each arm, >=5 of 38 analyzable subjects experiencing a grade ≥ 3 AE during the 1st year following TRT start would determine the respective TRT excessively toxic. For each arm this design provides 88% power with a 0.10 type I error rate.
Measured: From start of treatment to 1 year
Secondary outcomes (11)
1-year Primary Tumor Control Rate
Primary tumor control is defined as the lack of primary tumor failure. Primary tumor failure is defined as the development of in-field or marginal failure. Primary tumor control time is defined as time from randomization to the the date of primary tumor failure, last known follow-up (censored), or death without failure (competing risk). Primary tumor control rates are estimated using the cumulative incidence method.
Measured: From start of treatment to 1 year
1-year Overall Survival Rate
Overall survival time is defined as time from registration/randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method.
Measured: From start of treatment to 1 year
1-year Disease-free Survival Rate
Disease-free survival is defined as being alive without experiencing in-field, marginal, involved lobe, regional or metastatic failure, development of a second primary, or death due to any cause. Disease-free survival time is defined as time from randomization to the the date of first failure or last known follow-up (censored). Disease-free survival rates are estimated using the Kaplan-Meier method.
Measured: From start of treatment to 1 year
Change in Peak Standardized Uptake Value (SUV) at 12 Weeks Post-radiotherapy
Standardized uptake value (SUV) describes the level of biologic activity in a particular spot compared to activity elsewhere in the body. An SUV reading of 1 is considered normal cellular activity, with higher values indicating increased activity. Peak SUV is an average SUV computed within a fixed-size volume of interest (VOI), most often containing (and not necessarily centered on) the hottest pixel value. Peak SUV was measured from whole-body FDG-PET (fluorodeoxyglucose - positron emission tomography) scans that were required at baseline and requested (not required) at 12 weeks and 12 months post-radiotherapy. Change from baseline is calculated by subtracting the follow-up value from the baseline value. A positive change from baseline indicates decreased SUV.
Measured: Baseline and 12 weeks post-radiotherapy
Change in Peak Standardized Uptake Value (SUV) at One Year Post-radiotherapy
Standardized uptake value (SUV) describes the level of biologic activity in a particular spot compared to activity elsewhere in the body. An SUV reading of 1 is considered normal cellular activity, with higher values indicating increased activity. Peak SUV is an average SUV computed within a fixed-size volume of interest (VOI), most often containing (and not necessarily centered on) the hottest pixel value. Peak SUV was measured from whole-body FDG-PET scans that were required at baseline and requested (not required) at 12 weeks and 12 months post-radiotherapy. Change from baseline is calculated by subtracting the follow-up value from the baseline value. A positive change from baseline indicates decreased SUV. SUV does not have a unit.
Measured: Baseline and one year
Change in Normalized Standardized Uptake Value (SUV) at 12 Weeks
Standardized uptake value (SUV) describes the level of biologic activity in a particular spot compared to activity elsewhere in the body. An SUV reading of 1 is considered normal cellular activity, with higher values indicating increased activity. SUV was measured from whole-body FDG-PET scans that were required at baseline and requested (not required) at 12 weeks and 12 months post-radiotherapy. Normalized SUV = peak SUV of regions of interest / mean SUV of the aortic arch. Change from baseline is calculated by subtracting the follow-up value from the baseline value. A positive change from baseline indicates decreased SUV. SUV does not have a unit.
Measured: Baseline and 12 weeks
Change in Normalized Standardized Uptake Value (SUV) at One Year
Standardized uptake value (SUV) describes the level of biologic activity in a particular spot compared to activity elsewhere in the body. An SUV reading of 1 is considered normal cellular activity, with higher values indicating increased activity. SUV was measured from whole-body FDG-PET scans that were required at baseline and requested (not required) at 12 weeks and 12 months post-radiotherapy. Normalized SUV = peak SUV of regions of interest / mean SUV of the aortic arch. Change from baseline is calculated by subtracting the follow-up value from the baseline value. A positive change from baseline indicates decreased SUV. SUV does not have a unit.
Measured: Baseline and one year
Change in Percentage of Expected Forced Expiratory Volume in 1 Second (FEV1) by Best Observed Tumor Response at 6 Months Post-radiotherapy [Forced Expiratory Volume in 1 Second (FEV1)]
Forced expiratory volume (FEV1), a measure of pulmonary function, was reported as percentage of the value that would be expected for the normal general population of the same height, age, and sex. Change from baseline is calculated by subtracting the follow-up value from the baseline value. A positive change from baseline indicates decreased FEV1. Best observed tumor response was evaluated using the Revised Response Evaluation Criteria in Solid Tumors (RECIST) criteria v1.1 (http://ctep.cancer.gov/protocolDevelopment/docs/recist_guideline.pdf).
Measured: From start of treatment to 6 months post-radiotherapy
Change in Percentage of Expected Carbon Monoxide Diffusing Capacity (DLCO) by Best Observed Tumor Response at 6 Months Post-radiotherapy
Carbon monoxide diffusing capacity (DLCO), a measure of pulmonary function, was reported as percentage of the value that would be expected for the normal general population of the same height, age, and sex. Change from baseline is calculated by subtracting the follow-up value from the baseline value. A positive change from baseline indicates decreased DLCO. Best observed tumor response was evaluated using the Revised Response Evaluation Criteria in Solid Tumors (RECIST) criteria v1.1 (http://ctep.cancer.gov/protocolDevelopment/docs/recist_guideline.pdf).
Measured: From start of treatment to 6 months post-radiotherapy
Association Between Biomarkers and Primary Tumor Control Rate
Measured: From start of treatment to 1 year
Association Between Biomarkers and Grade 2+ Radiation Pneumonitis
Measured: From start of treatment to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2009 (estimated)
- Study startNov 2009
- Primary completionAug 2012
- Study completion14 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 94 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radiation Therapy Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI), NRG Oncology
- Responsible party
- Sponsor
- Investigators
- Gregory Videtic, MD, Study chair, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00960999
- Sponsor's protocol ID
- RTOG-0915
- Other IDs
- CDR0000652101
- Status last verified
- Feb 2020
- First submitted
- 16 Aug 2009
- Last updated
- 4 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Videtic GM, Hu C, Singh AK, Chang JY, Parker W, Olivier KR, Schild SE, Komaki R, Urbanic JJ, Timmerman RD, Choy H. A Randomized Phase 2 Study Comparing 2 Stereotactic Body Radiation Therapy Schedules for Medically Inoperable Patients With Stage I Peripheral Non-Small Cell Lung Cancer: NRG Oncology RTOG 0915 (NCCTG N0927). Int J Radiat Oncol Biol Phys. 2015 Nov 15;93(4):757-64. doi: 10.1016/j.ijrobp.2015.07.2260. Epub 2015 Jul 17.
PubMed 26530743
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Study Comparing 2 Stereotactic Body Radiation Therapy (SBRT) Schedules for Medically Inoperable Patients With Stage I Peripheral Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT00960999
- Acronym / sponsor ID
- RTOG-0915
- Conditions
- Lung Cancer
- Keywords
- stage I non-small cell lung cancer, squamous cell lung cancer, adenocarcinoma of the lung, large cell lung cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 94 participants (actual)
- Lead sponsor
- Radiation Therapy Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI), NRG Oncology
- Study start
- Nov 2009 (actual)
- Primary completion
- Aug 2012 (actual)
- Study completion
- 14 May 2018 (actual)
- First posted
- 18 Aug 2009 (estimated)
- Results
- Posted 4 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. It is not yet known which regimen of stereotactic body radiation therapy is more effective in treating patients with non-small cell lung cancer.
PURPOSE: This randomized phase II trial is studying the side effects of two radiation therapy regimens and to see how well they work in treating patients with stage I non-small cell lung cancer.
Detailed description
OBJECTIVES:
Primary
- To determine the 1-year rate of ≥ grade 3 adverse events that are definitely, probably, or possibly related to treatment with single fraction vs multiple fraction stereotactic body radiotherapy in medically inoperable patients with stage I peripheral non-small cell lung cancer.
Secondary
- To estimate the 1-year primary tumor control rate in these patients.
- To estimate the 1-year overall survival and disease-free survival rate of these patients.
- To assess FDG-PET (fluorodeoxyglucose - positron emission tomography) standardized uptake value changes as a measure of treatment response and outcomes.
- To determine pulmonary function changes by treatment arm and response.
- To determine the association between biomarkers and primary tumor control and/or ≥ grade 2 radiation pneumonitis.
OUTLINE: This is a multicenter study. Patients are stratified according to Zubrod performance status (0 vs 1 vs 2) and T stage (T1 vs T2). Patients are randomized to 1 of 2 treatment arms.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Single-fraction SBRT (34 Gy) | Experimental | Radiation: Single-fraction stereotactic body radiation therapy (SBRT)Single-fraction stereotactic body radiation therapy (SBRT) of 34 Gy |
| Multiple-fraction SBRT (48 Gy) | Experimental | Radiation: Multiple-fraction stereotactic body radiation therapy (SBRT)Multiple-fraction stereotactic body radiation therapy (SBRT) given in four daily 12 Gy fractions for a total dose of 48 Gy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Histological confirmation (by biopsy or cytology) of non-small cell lung cancer (NSCLC) prior to treatment; the following primary cancer types are eligible: squamous cell carcinoma, adenocarcinoma, large cell carcinoma, large cell neuroendocrine, or non-small cell carcinoma not otherwise specified; Note: although bronchioloalveolar cell carcinoma is a subtype of NSCLC, patients with the pure type of this malignancy are excluded from this study because the spread of this cancer between adjacent airways is difficult to target on computed tomography (CT).
- Stage T1, N0, M0 or T2 (≤ 5 cm), N0, M0, (AJCC Staging, 6th Ed.), based upon #3.
- Minimum diagnostic workup:
- Patients with hilar or mediastinal lymph nodes ≤ 1cm and no abnormal hilar or mediastinal uptake on PET will be considered N0. Patients with > 1 cm hilar or mediastinal lymph nodes on CT or abnormal PET (including suspicious but non-diagnostic uptake) may still be eligible if directed tissue biopsy of all abnormally identified areas are negative for cancer.
- The patient's resectable NSCLC must be considered medically inoperable by an experienced thoracic cancer clinician (a thoracic surgeon, medical oncologist, radiation oncologist, or pulmonologist) or a standard lobectomy and mediastinal lymph node dissection/sampling procedure. The patient may have underlying physiological medical problems that would prohibit a surgery due to a low probability of tolerating general anesthesia, the operation, the postoperative recovery period, or the removal of adjacent functioning lung. These types of patients with severe underlying health problems are deemed "medically inoperable." Standard justification for deeming a patient medically inoperable based on pulmonary function for surgical resection of NSCLC may include any of the following:
Key exclusion criteria (9 listed)
- Patients with T2 primary tumors > 5 cm or involving the central plural and/or structures of the mediastinum;
- The primary tumor of any T-stage within or touching the zone of the proximal bronchial tree, defined as a volume 2 cm in all directions around the proximal bronchial tree (carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus, right and left lower lobe bronchi);
- Direct evidence of regional or distant metastases after appropriate staging studies, or synchronous primary malignancy or prior malignancy in the past 2 years except for invasive malignancy that has been treated definitively and the patient remains disease free for > 3 years with life expectancy of > 3 years or carcinoma in situ or early stage skin cancers that have been treated definitively;
- Previous radiotherapy to the lung or mediastinum;
- Previous chemotherapy for this lung or mediastinum tumor; chemotherapy for another invasive malignancy is permitted if it has been treated definitively and the patient has remained disease free for > 3 years.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Single-fraction stereotactic body radiation therapy (SBRT)34 Gy in 1 fraction to the prescription line at the edge of the planning target volume (PTV). The maximum dose must exist within the PTV, and the prescription isodose surface must be ≥ 60% and < 90% of the maximum dose. 99% of the PTV must receive a minimum of 90% of the prescription dose. The maximum dose to any point ≥ 2 cm away from the PTV in any direction must be at least < 50% of the prescription dose. The percent of the lungs (excluding PTV) receiving 20 Gy or more must be < 10%. | Radiation | Single-fraction SBRT (34 Gy) |
| Multiple-fraction stereotactic body radiation therapy (SBRT)48 Gy in four 12 Gy fractions to the prescription line at the edge of the planning target volume (PTV). Treatments are given on 4 consecutive calendar days, but at least 18 hours apart. The maximum dose must exist within the PTV, and the prescription isodose surface must be ≥ 60% and < 90% of the maximum dose. 99% of the PTV must receive a minimum of 90% of the prescription dose. The maximum dose to any point ≥ 2 cm away from the PTV in any direction must be at least < 50% of the prescription dose. The percent of the lungs (excluding PTV) receiving 20 Gy or more must be < 10%. | Radiation | Multiple-fraction SBRT (48 Gy) |
Primary outcome
Counts of ≥ Grade 3 Adverse Events (AE) Graded by CTCAE v4 (Common Terminology Criteria for Adverse Events) That Are Definitely, Probably, or Possibly Related to Treatment (DPPRT)
Time frame: From start of treatment to 1 year
Number of patients with ≥ grade 3 AE occurring within 1 year of treatment (TRT) start and reported as DPPRT among this subset of CTCAE v4: pericardial effusion, pericarditis, restrictive cardiomyopathy, dysphagia, esophagitis, esophageal fistula/obstruction/perforation/stenosis/ulcer/hemorrhage, rib fracture, brachial plexopathy, recurrent laryngeal nerve palsy, myelitis, atelectasis, bronchopulmonary/mediastinal/pleural/tracheal hemorrhage, bronchial/pulmonary/bronchopleural/tracheal fistula, hypoxia, bronchial/tracheal obstruction, pleural effusion, pneumonitis, pulmonary fibrosis, skin ulceration (thorax only), FEV1 (Forced Expiratory Volume) or FVC (forced vital capacity) decline, or grade 5 related to TRT. Each arm is considered independently. For each arm, >=5 of 38 analyzable subjects experiencing a grade ≥ 3 AE during the 1st year following TRT start would determine the respective TRT excessively toxic. For each arm this design provides 88% power with a 0.10 type I error rate.
11 secondary outcomes
1-year Primary Tumor Control Rate
Time frame: From start of treatment to 1 year
1-year Overall Survival Rate
Time frame: From start of treatment to 1 year
1-year Disease-free Survival Rate
Time frame: From start of treatment to 1 year
Change in Peak Standardized Uptake Value (SUV) at 12 Weeks Post-radiotherapy
Time frame: Baseline and 12 weeks post-radiotherapy
Change in Peak Standardized Uptake Value (SUV) at One Year Post-radiotherapy
Time frame: Baseline and one year
Change in Normalized Standardized Uptake Value (SUV) at 12 Weeks
Time frame: Baseline and 12 weeks
Change in Normalized Standardized Uptake Value (SUV) at One Year
Time frame: Baseline and one year
Change in Percentage of Expected Forced Expiratory Volume in 1 Second (FEV1) by Best Observed Tumor Response at 6 Months Post-radiotherapy [Forced Expiratory Volume in 1 Second (FEV1)]
Time frame: From start of treatment to 6 months post-radiotherapy
Change in Percentage of Expected Carbon Monoxide Diffusing Capacity (DLCO) by Best Observed Tumor Response at 6 Months Post-radiotherapy
Time frame: From start of treatment to 6 months post-radiotherapy
Association Between Biomarkers and Primary Tumor Control Rate
Time frame: From start of treatment to 1 year
Association Between Biomarkers and Grade 2+ Radiation Pneumonitis
Time frame: From start of treatment to 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26530743Videtic GM, Hu C, Singh AK, Chang JY, Parker W, Olivier KR, Schild SE, Komaki R, Urbanic JJ, Timmerman RD, Choy H. A Randomized Phase 2 Study Comparing 2 Stereotactic Body Radiation Therapy Schedules for Medically Inoperable Patients With Stage I Peripheral Non-Small Cell Lung Cancer: NRG Oncology RTOG 0915 (NCCTG N0927). Int J Radiat Oncol Biol Phys. 2015 Nov 15;93(4):757-64. doi: 10.1016/j.ijrobp.2015.07.2260. Epub 2015 Jul 17.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gregory Videtic, MD study chair
The Cleveland Clinic
38 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Single-fraction stereotactic body radiation therapy (SBRT) and Multiple-fraction stereotactic body radiation therapy (SBRT) in people with Lung Cancer, run by Radiation Therapy Oncology Group at 38 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 9 exclusion criteria. 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 4 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States, Canada. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 4 Nov 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?
Counts of ≥ Grade 3 Adverse Events (AE) Graded by CTCAE v4 (Common Terminology Criteria for Adverse Events) That Are Definitely, Probably, or Possibly Related to Treatment (DPPRT) (time frame: From start of treatment to 1 year). 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 NCT00960999, which also lists 1 linked publication.
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 4 Mar 2020.