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Stereotactic Body Radiation Therapy in Treating Patients With Inoperable Stage I or Stage II Non-Small Cell Lung Cancer

Primary Purpose

Lung Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
stereotactic body radiation therapy
Sponsored by
Radiation Therapy Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring stage I non-small cell lung cancer, stage II non-small cell lung cancer, squamous cell lung cancer, large cell lung cancer, adenocarcinoma of the lung, bronchoalveolar cell lung cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) The following primary cancer subtypes are eligible: Squamous cell carcinoma Adenocarcinoma Large cell carcinoma Bronchoalveolar cell carcinoma Non-small cell carcinoma not otherwise specified Stage I or II disease based on 1 of the following tumor node metastasis (TNM) stage criteria: T1, N0, M0 T2 (≤ 5 cm), N0, M0 T3 (≤ 5 cm), N0, M0 (chest wall primary tumors only) No primary tumor of any T-stage within or touching the zone of the proximal bronchial tree* NOTE: *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, and right and left lower lobe bronchi) No primary T3 tumors involving the central chest (≤ 2 cm toward carina invasion) or structures of the mediastinum Any hilar or mediastinal lymph nodes > 1 cm on CT scan OR demonstrating suspicious uptake on positron-emission tomography scan must be biopsied and confirmed negative for NSCLC The primary tumor must be deemed technically resectable with a reasonable possibility of obtaining a gross total resection with negative margins (defined as a potentially curative resection (PCR)) Deemed medically inoperable based on pulmonary function for surgical resection of NSCLC secondary to an underlying physiological problem, including any of the following medical conditions*: Baseline forced expiratory volume (FEV)_1< 40% of predicted Postoperative predicted FEV_1 < 30% of predicted Severely reduced diffusion capacity Baseline hypoxemia and/or hypercapnia Exercise oxygen consumption < 50% of predicted Severe pulmonary hypertension Diabetes mellitus with severe end organ damage Severe cerebral, cardiac, or peripheral vascular disease Severe chronic heart disease NOTE: *Patients who refuse a PCR due to preference, ideology, emotional or psychological issues, mental illness, or inability to give informed consent are not eligible No evidence of regional or distant metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-2 Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified Cardiovascular See Disease Characteristics No active pericardial infection Pulmonary See Disease Characteristics No active pulmonary infection Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active systemic infection No other concurrent illness that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent biologic therapy No concurrent vaccine therapy Chemotherapy No concurrent chemotherapy Endocrine therapy Not specified Radiotherapy No prior lung or mediastinal radiotherapy No concurrent standard fractionated radiotherapy No concurrent intensity modulated radiotherapy No concurrent cobalt-60 or charged particle beams (including electrons, protons, or heavier ions) Surgery See Disease Characteristics No concurrent surgery Other No other concurrent antineoplastic therapy

Sites / Locations

  • James P. Wilmot Cancer Center at University of Rochester Medical Center
  • M.D. Anderson Cancer Center at University of Texas

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Stereotactic body radiation therapy (SBRT)

Arm Description

20 Gy per fraction for 3 fractions over 1.5-2 weeks, for a total of 60 Gy

Outcomes

Primary Outcome Measures

Local Control at 2 Years
Local control is defined as absence of local failure, which is defined as the combination of primary tumor failure (PTF) or involved lobe failure (ILF). PTF was defined based on meeting two criteria: 1. Local enlargement defined as ≥ 20% increase in the longest diameter of the gross tumor volume (GTV) per computerized tomography (CT), and 2. Evidence of tumor viability. Tumor viability could be affirmed by either demonstrating positron emission tomography (PET) imaging with uptake of a similar intensity as the pretreatment staging PET, or by repeat biopsy confirming carcinoma. PTF included marginal failures occurring within 1 cm of the planning target volume (PTV). ILF is defined as failure beyond the primary tumor but within the involved lobe. Local control time is defined as time from start of treatment to the the date of local recurrence, last known follow-up (censored), or death without local failure (censored). Rates are estimated using the Kaplan-Meier method.

Secondary Outcome Measures

Proportion of Subjects With Specified Adverse Events
Specified adverse events are defined as any treatment-related adverse events that are grade 4, grade 5, or any of the following treatment-related grade 3 adverse events: Gastrointestinal: dysphagia, esophagitis, esophageal stricture, esophageal ulceration; Cardiac: pericarditis, pericardial effusion, cardiomyopathy, ventricular dysfunction; Neurologic: myelitis, neuropathy (cranial and motor) Hemorrhage: pulmonary or upper respiratory Pulmonary: decline in pulmonary function as measured by pulmonary function tests, pneumonitis, pulmonary fibrosis, hypoxemia, pleural effusion. Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The Common Terminology Criteria for Adverse Events (CTCAE) v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
Rate of Local Recurrence at 2 Years
Local failure is defined as the combination of primary tumor failure (PTF) or involved lobe failure (ILF). PTF was defined based on meeting two criteria: 1. Local enlargement defined as ≥ 20% increase in the longest diameter of the gross tumor volume (GTV) per computerized tomography (CT), and 2. Evidence of tumor viability. Tumor viability could be affirmed by either demonstrating positron emission tomography (PET) imaging with uptake of a similar intensity as the pretreatment staging PET, or by repeat biopsy confirming carcinoma. PTF included marginal failures occurring within 1 cm of the planning target volume (PTV). ILF is defined as failure beyond the primary tumor but within the involved lobe. Time to local recurrence is defined as time from start of treatment to the the date of local recurrence, last known follow-up (censored), or death without local recurrence (censored).
Rate of Regional Recurrence at 2 Years
Regional recurrence is defined as hilar, mediastinal, and supraclavicular nodal failure.Time to regional recurrence is defined as time from start of treatment to the date of first regional recurrence, last known follow-up (censored), or death without regional recurrence (competing risk). Rates are estimated using the cumulative incidence method.
Rate of Disseminated Recurrence at 2 Years
Disseminated recurrence is defined as uninvolved lobe failures and failures beyond the lungs and regional lymph nodes. Time to disseminated recurrence is defined as time from start of treatment to the the date of disseminated recurrence, last known follow-up (censored), or death without disseminated recurrence (competing risk). Rates are estimated using the cumulative incidence method.
Rate of Disease-free Survival at 2 Years
Disease is defined as local or regional progression or development of distant metastases. Disease-free survival time is defined as time from start of treatment to the date of disease, death, or last known follow-up (censored). Disease-free survival rates are estimated using the Kaplan-Meier method.
Rate of Overall Survival at 2 Years
Overall survival time is defined as time from start of treatment to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.

Full Information

First Posted
July 8, 2004
Last Updated
December 21, 2018
Sponsor
Radiation Therapy Oncology Group
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00087438
Brief Title
Stereotactic Body Radiation Therapy in Treating Patients With Inoperable Stage I or Stage II Non-Small Cell Lung Cancer
Official Title
A Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) in the Treatment of Patients With Medically Inoperable Stage I/II Non-Small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
May 2004 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
December 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radiation Therapy Oncology Group
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Stereotactic body radiation therapy may be able to deliver x-rays directly to the tumor and cause less damage to normal tissue. PURPOSE: This phase II trial is studying how well stereotactic body radiation therapy works in treating patients with inoperable stage I or stage II non-small cell lung cancer.
Detailed Description
OBJECTIVES: Primary Determine whether treatment with stereotactic body radiotherapy results in acceptable local control (i.e., ≥ 80%) in patients with medically inoperable stage I or II non-small cell lung cancer. Secondary Determine treatment-related toxicity in patients treated with this therapy. Determine disease-free survival, overall survival, and patterns of failure in patients treated with this therapy. OUTLINE: This is a multicenter study. Patients receive 3 fractions of stereotactic body radiotherapy over 8-14 days in the absence of disease progression or unacceptable toxicity. Patients are followed up at 6 and 12 weeks, every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 52 patients will be accrued for this study within 26 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer
Keywords
stage I non-small cell lung cancer, stage II non-small cell lung cancer, squamous cell lung cancer, large cell lung cancer, adenocarcinoma of the lung, bronchoalveolar cell lung cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
59 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Stereotactic body radiation therapy (SBRT)
Arm Type
Experimental
Arm Description
20 Gy per fraction for 3 fractions over 1.5-2 weeks, for a total of 60 Gy
Intervention Type
Radiation
Intervention Name(s)
stereotactic body radiation therapy
Primary Outcome Measure Information:
Title
Local Control at 2 Years
Description
Local control is defined as absence of local failure, which is defined as the combination of primary tumor failure (PTF) or involved lobe failure (ILF). PTF was defined based on meeting two criteria: 1. Local enlargement defined as ≥ 20% increase in the longest diameter of the gross tumor volume (GTV) per computerized tomography (CT), and 2. Evidence of tumor viability. Tumor viability could be affirmed by either demonstrating positron emission tomography (PET) imaging with uptake of a similar intensity as the pretreatment staging PET, or by repeat biopsy confirming carcinoma. PTF included marginal failures occurring within 1 cm of the planning target volume (PTV). ILF is defined as failure beyond the primary tumor but within the involved lobe. Local control time is defined as time from start of treatment to the the date of local recurrence, last known follow-up (censored), or death without local failure (censored). Rates are estimated using the Kaplan-Meier method.
Time Frame
From the start of treatment to 2 years
Secondary Outcome Measure Information:
Title
Proportion of Subjects With Specified Adverse Events
Description
Specified adverse events are defined as any treatment-related adverse events that are grade 4, grade 5, or any of the following treatment-related grade 3 adverse events: Gastrointestinal: dysphagia, esophagitis, esophageal stricture, esophageal ulceration; Cardiac: pericarditis, pericardial effusion, cardiomyopathy, ventricular dysfunction; Neurologic: myelitis, neuropathy (cranial and motor) Hemorrhage: pulmonary or upper respiratory Pulmonary: decline in pulmonary function as measured by pulmonary function tests, pneumonitis, pulmonary fibrosis, hypoxemia, pleural effusion. Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The Common Terminology Criteria for Adverse Events (CTCAE) v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
Time Frame
From randomization to last follow-up. Analysis occurred after all patients had been on study for at least 2 years. Maximum follow-up at time of analysis was 4.2 years.
Title
Rate of Local Recurrence at 2 Years
Description
Local failure is defined as the combination of primary tumor failure (PTF) or involved lobe failure (ILF). PTF was defined based on meeting two criteria: 1. Local enlargement defined as ≥ 20% increase in the longest diameter of the gross tumor volume (GTV) per computerized tomography (CT), and 2. Evidence of tumor viability. Tumor viability could be affirmed by either demonstrating positron emission tomography (PET) imaging with uptake of a similar intensity as the pretreatment staging PET, or by repeat biopsy confirming carcinoma. PTF included marginal failures occurring within 1 cm of the planning target volume (PTV). ILF is defined as failure beyond the primary tumor but within the involved lobe. Time to local recurrence is defined as time from start of treatment to the the date of local recurrence, last known follow-up (censored), or death without local recurrence (censored).
Time Frame
From the start of treatment to 2 years
Title
Rate of Regional Recurrence at 2 Years
Description
Regional recurrence is defined as hilar, mediastinal, and supraclavicular nodal failure.Time to regional recurrence is defined as time from start of treatment to the date of first regional recurrence, last known follow-up (censored), or death without regional recurrence (competing risk). Rates are estimated using the cumulative incidence method.
Time Frame
From the start of treatment to 2 years
Title
Rate of Disseminated Recurrence at 2 Years
Description
Disseminated recurrence is defined as uninvolved lobe failures and failures beyond the lungs and regional lymph nodes. Time to disseminated recurrence is defined as time from start of treatment to the the date of disseminated recurrence, last known follow-up (censored), or death without disseminated recurrence (competing risk). Rates are estimated using the cumulative incidence method.
Time Frame
From the start of treatment to 2 years
Title
Rate of Disease-free Survival at 2 Years
Description
Disease is defined as local or regional progression or development of distant metastases. Disease-free survival time is defined as time from start of treatment to the date of disease, death, or last known follow-up (censored). Disease-free survival rates are estimated using the Kaplan-Meier method.
Time Frame
From the start of treatment to 2 years
Title
Rate of Overall Survival at 2 Years
Description
Overall survival time is defined as time from start of treatment to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.
Time Frame
From the start of treatment to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) The following primary cancer subtypes are eligible: Squamous cell carcinoma Adenocarcinoma Large cell carcinoma Bronchoalveolar cell carcinoma Non-small cell carcinoma not otherwise specified Stage I or II disease based on 1 of the following tumor node metastasis (TNM) stage criteria: T1, N0, M0 T2 (≤ 5 cm), N0, M0 T3 (≤ 5 cm), N0, M0 (chest wall primary tumors only) No primary tumor of any T-stage within or touching the zone of the proximal bronchial tree* NOTE: *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, and right and left lower lobe bronchi) No primary T3 tumors involving the central chest (≤ 2 cm toward carina invasion) or structures of the mediastinum Any hilar or mediastinal lymph nodes > 1 cm on CT scan OR demonstrating suspicious uptake on positron-emission tomography scan must be biopsied and confirmed negative for NSCLC The primary tumor must be deemed technically resectable with a reasonable possibility of obtaining a gross total resection with negative margins (defined as a potentially curative resection (PCR)) Deemed medically inoperable based on pulmonary function for surgical resection of NSCLC secondary to an underlying physiological problem, including any of the following medical conditions*: Baseline forced expiratory volume (FEV)_1< 40% of predicted Postoperative predicted FEV_1 < 30% of predicted Severely reduced diffusion capacity Baseline hypoxemia and/or hypercapnia Exercise oxygen consumption < 50% of predicted Severe pulmonary hypertension Diabetes mellitus with severe end organ damage Severe cerebral, cardiac, or peripheral vascular disease Severe chronic heart disease NOTE: *Patients who refuse a PCR due to preference, ideology, emotional or psychological issues, mental illness, or inability to give informed consent are not eligible No evidence of regional or distant metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-2 Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified Cardiovascular See Disease Characteristics No active pericardial infection Pulmonary See Disease Characteristics No active pulmonary infection Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active systemic infection No other concurrent illness that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent biologic therapy No concurrent vaccine therapy Chemotherapy No concurrent chemotherapy Endocrine therapy Not specified Radiotherapy No prior lung or mediastinal radiotherapy No concurrent standard fractionated radiotherapy No concurrent intensity modulated radiotherapy No concurrent cobalt-60 or charged particle beams (including electrons, protons, or heavier ions) Surgery See Disease Characteristics No concurrent surgery Other No other concurrent antineoplastic therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert D. Timmerman, MD
Organizational Affiliation
Simmons Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
James P. Wilmot Cancer Center at University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
M.D. Anderson Cancer Center at University of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19695451
Citation
Hurkmans CW, Cuijpers JP, Lagerwaard FJ, Widder J, van der Heide UA, Schuring D, Senan S. Dosimetric evaluation of heterogeneity corrections for RTOG 0236: stereotactic body radiotherapy of inoperable Stage I-II non-small-cell lung cancer. In reply to Dr. Xiao et al. Int J Radiat Oncol Biol Phys. 2009 Sep 1;75(1):318; author reply 318. doi: 10.1016/j.ijrobp.2009.05.050. No abstract available.
Results Reference
background
PubMed Identifier
16982540
Citation
Timmerman R, Galvin J, Michalski J, Straube W, Ibbott G, Martin E, Abdulrahman R, Swann S, Fowler J, Choy H. Accreditation and quality assurance for Radiation Therapy Oncology Group: Multicenter clinical trials using Stereotactic Body Radiation Therapy in lung cancer. Acta Oncol. 2006;45(7):779-86. doi: 10.1080/02841860600902213.
Results Reference
background
PubMed Identifier
20233825
Citation
Timmerman R, Paulus R, Galvin J, Michalski J, Straube W, Bradley J, Fakiris A, Bezjak A, Videtic G, Johnstone D, Fowler J, Gore E, Choy H. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA. 2010 Mar 17;303(11):1070-6. doi: 10.1001/jama.2010.261.
Results Reference
result
PubMed Identifier
19251095
Citation
Xiao Y, Papiez L, Paulus R, Timmerman R, Straube WL, Bosch WR, Michalski J, Galvin JM. Dosimetric evaluation of heterogeneity corrections for RTOG 0236: stereotactic body radiotherapy of inoperable stage I-II non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2009 Mar 15;73(4):1235-42. doi: 10.1016/j.ijrobp.2008.11.019.
Results Reference
result
Citation
Timmerman RD, Paulus R, Galvin J, et al.: Toxicity analysis of RTOG 0236 using stereotactic body radiation therapy to treat medically inoperable early stage lung cancer patients. [Abstract] Int J Radiat Oncol Biol Phys 69 (3 Suppl): A-151, S86, 2007.
Results Reference
result

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Stereotactic Body Radiation Therapy in Treating Patients With Inoperable Stage I or Stage II Non-Small Cell Lung Cancer

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