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Stereotactic Body Radiation Therapy in Treating Patients With Stage I or Stage II Non-Small Cell Lung Cancer That Can Be Removed By Surgery

Primary Purpose

Lung Cancer

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

SBRT

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, adenocarcinoma of the lung, large cell lung cancer, squamous cell lung cancer, adenosquamous 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, including any of the following primary tumor types:
- Squamous cell carcinoma
- Adenocarcinoma
- Large cell carcinoma
- Large cell neuroendocrine tumor
- Non-small cell carcinoma not otherwise specified
No pure type bronchoalveolar cell carcinoma
Stage I or II disease based on 1 of the following combinations of primary tumor, regional nodes, metastasis (TNM) staging:
- T1, N0, M0
- T2 (≤ 5 cm), N0, M0
- T3 (≤ 5 cm), N0, M0 (chest wall primary tumors only)
No T2 or T3 primary tumors > 5 cm or T3 primary tumors involving the central chest and structures of the mediastinum
No primary tumor of any T-stage within or touching the zone of the proximal bronchial tree, defined as a volume of 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, or right and left lower lobe bronchi)
Patients with hilar or mediastinal lymph nodes ≤ 1 cm AND no abnormal hilar or mediastinal uptake on positron emission tomography (PET) scan will be considered N0
- Patients with > 1 cm hilar or mediastinal lymph nodes on CT scan OR abnormal PET scan (including suspicious but nondiagnostic uptake) will still be eligible if directed tissue biopsies of all abnormally identified areas are negative for cancer
No direct evidence of regional or distant metastases after appropriate staging studies
Considered a reasonable candidate for surgical resection of the primary tumor, according to the following criteria:
- Primary tumor predicted to be technically resectable with a high likelihood of negative surgical margins (as determined by a qualified thoracic surgeon)
- Baseline forced expiratory volume (FEV)_1 > 35% predicted
- Postoperative predicted FEV_1 > 30% predicted
- Diffusion capacity > 35% predicted
- No hypoxemia (e.g., partial pressure of arterial oxygen (PaO2) of ≤ 60 mm Hg) and/or hypercapnia (e.g., partial pressure of arterial carbon dioxide (PaCO2) > 50 mm Hg) at baseline
- No severe pulmonary hypertension
- No severe cerebral, cardiac, or peripheral vascular disease
- No severe chronic heart disease
Pleural effusion, if present, must be deemed too small to tap under CT scan guidance and must not be evident on chest x-ray
- Pleural effusion that appears on chest x-ray will be allowed only after thoracotomy or other invasive procedure

PATIENT CHARACTERISTICS:

Zubrod performance status 0-1
Absolute neutrophil count ≥ 1,800/mm³
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 8.0 g/dL (transfusion allowed)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No synchronous primary or other invasive malignancy within the past 3 years other than nonmelanoma skin cancer or in situ cancer
No active systemic, pulmonary, or pericardial infection
No weight loss > 5% for any reason within the past 3 months

PRIOR CONCURRENT THERAPY:

No prior radiotherapy for lung cancer
- Prior radiotherapy as part of treatment for head and neck cancer, breast cancer, or other non-lung cancer is allowed provided there will not be significant overlap with the stereotactic body radiotherapy fields
No prior chemotherapy or surgical resection for this lung cancer
No other concurrent local or regional antineoplastic therapy (including standard fractionated radiotherapy, non-approved systemic therapy, and surgery), except at disease progression

Sites / Locations

UAB Comprehensive Cancer Center
Alta Bates Summit Comprehensive Cancer Center
Mercy Cancer Center at Mercy San Juan Medical Center
Marin Cancer Institute at Marin General Hospital
University of California Davis Cancer Center
Memorial Hospital of South Bend
Lucille P. Markey Cancer Center at University of Kentucky
Greenebaum Cancer Center at University of Maryland Medical Center
Lacks Cancer Center at Saint Mary's Health Care
William Beaumont Hospital - Royal Oak Campus
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
NYU Cancer Institute at New York University Medical Center
Stony Brook University Cancer Center
Wake Forest University Comprehensive Cancer Center
Penn State Cancer Institute at Milton S. Hershey Medical Center
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
INOVA Alexandria Hospital
St. Joseph Cancer Center
Medical College of Wisconsin Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SBRT

Arm Description

Stereotactic body radiation therapy (SBRT)

Outcomes

Primary Outcome Measures

Primary Tumor Control at 2 Years

Primary tumor control is defined as the absence of primary tumor failure by 2 years after the start of SBRT. Primary tumor failure was considered as the development of either failure within the SBRT treatment fields (in-field failure) or failure within 1.0 cm of the treatment field (marginal failure). An acceptable tumor control rate at 2 years was considered to be 90% (monthly hazard of 0.00439), and an unacceptable rate was 70% (monthly hazard of 0.01486). A one-sided type 1 error of 0.05 and statistical power of 90% was used. A one-sided Z-test was used to determine if the difference between the logarithm of the observed hazard rate and the logarithm of the hypothesized hazard rate of 0.01486 was statistically significant.

Secondary Outcome Measures

Rate of Treatment-related Grade 3 or 4 Toxicity

The development of any treatment-related toxicity from among the following: Gastrointestinal: dysphagia, esophagitis, esophageal stricture/stenosis, esophageal ulceration; Cardiac: pericarditis, pericardial effusion, restrictive cardiomyopathy, ventricular dysfunction (left ventricular diastolic dysfunction, left ventricular systolic dysfunction, right ventricular dysfunction); Neurologic: myelitis, neuropathy (cranial and motor); Hemorrhage: pulmonary or upper respiratory; Pulmonary: decline in pulmonary function as measured by pulmonary function tests (DLCO, FEV1,FVC), pneumonitis, pulmonary fibrosis, hypoxia, pleural effusion, cough, and dyspnea; Any grade 4 or 5 adverse event attributed to the therapy

Other Grade 3-5 Adverse Events

The development of any treatment-related toxicity not from among the following: Gastrointestinal: dysphagia, esophagitis, esophageal stricture/stenosis, esophageal ulceration; Cardiac: pericarditis, pericardial effusion, restrictive cardiomyopathy, ventricular dysfunction (left ventricular diastolic dysfunction, left ventricular systolic dysfunction, right ventricular dysfunction); Neurologic: myelitis, neuropathy (cranial and motor); Hemorrhage: pulmonary or upper respiratory; Pulmonary: decline in pulmonary function as measured by pulmonary function tests (DLCO, FEV1,FVC), pneumonitis, pulmonary fibrosis, hypoxia, pleural effusion, cough, and dyspnea; Any grade 4 or 5 adverse event attributed to the therapy

Primary Tumor Failure (PTF), Marginal Failure (MF), Regional Failure (RF), Metastatic Dissemination (MD), Disease-free Survival (DFS), and Overall Survival (OS) at 2 Years

PTF: the development of either failure within the SBRT treatment fields (in-field failure) or failure within 1.0 cm of the treatment field (marginal failure) within the first two years after start of SBRT. RF: the development of measurable tumor within lymph nodes along the natural lymphatic drainage typical for the location of the treated primary disease only with dimension of at least 1.0 cm on imaging studies (preferably CT scans) within the lung, bronchial hilum, or the mediastinum within the first two years after start of SBRT. MD: the appearance after protocol therapy of cancer deposits characteristic of metastatic dissemination from non-small cell lung cancer within the first two years after start of SBRT. DFS: the state of being alive without development of progressive disease, with failure considered the earliest development of either progression or death. OS: the state of being alive, with failure is considered death due to any cause.

Level of Comorbidity Burden on Morbidity and Efficacy

Assessment of Predictive Value of Blood Markers for Primary Tumor Control at 2 Years and Treatment-related Adverse Events ≥ Grade 2

Assess if blood markers prior to, during the course of treatment (between the second and the last dose of SBRT), and at the first follow-up after SBRT predict 2 year primary tumor control and predict for grade ≥ 2 treatment-related adverse events. Unfortunately, there were not enough specimens submitted to perform this analysis. The specimens that were collected remain in the NRG Oncology Biobank and are available to be combined with other specimens from other studies for an appropriately powered project.

Full Information

NCT ID

NCT00551369

First Posted

October 30, 2007

Last Updated

April 9, 2019

Sponsor

Radiation Therapy Oncology Group

Collaborators

National Cancer Institute (NCI), NRG Oncology

1. Study Identification

Unique Protocol Identification Number

NCT00551369

Brief Title

Stereotactic Body Radiation Therapy in Treating Patients With Stage I or Stage II Non-Small Cell Lung Cancer That Can Be Removed By Surgery

Official Title

A Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) in the Treatment of Patients With Operable Stage I/II Non-Small Cell Lung Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Completed

Study Start Date

December 2007 (Actual)

Primary Completion Date

May 2012 (Actual)

Study Completion Date

May 14, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Radiation Therapy Oncology Group

Collaborators

National Cancer Institute (NCI), NRG Oncology

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

RATIONALE: Stereotactic body radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue near the tumor. PURPOSE: This phase II trial is studying how well stereotactic body radiation therapy works in treating patients with stage I or stage II non-small cell lung cancer that can be removed by surgery.

Detailed Description

OBJECTIVES: Primary Determine whether treatment with radiotherapy involving a high biological dose with limited treatment volume (using stereotactic body radiotherapy [SBRT] techniques) achieves acceptable primary tumor control (i.e., ≥ 90% at 2 years) in patients with resectable early-stage non-small cell lung cancer. Secondary Determine whether treatment with radiotherapy involving a high biological dose with limited treatment volume (using SBRT techniques) achieves acceptable treatment-related toxicity. Estimate the disease-free survival and the overall survival rate at 2 years. Observe patterns of failure in the first 2 years. Assess the level of comorbidity burden on morbidity and efficacy. Determine if blood markers prior to, during the course of treatment (between the second and the last dose of SBRT), and at the first follow-up after SBRT predict 2-year primary tumor control and predict for grade ≥ 2 treatment-related toxicities OUTLINE: This is a multicenter study. Patients receive 3 fractions of stereotactic body radiotherapy over 14 days. Patients with disease progression undergo surgical resection as salvage local therapy. After completion of study therapy, patients are followed every 3 months for 2 years, every 6 months for 3 years and then annually thereafter.

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, adenocarcinoma of the lung, large cell lung cancer, squamous cell lung cancer, adenosquamous 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

33 (Actual)

8. Arms, Groups, and Interventions

Arm Title

SBRT

Arm Type

Experimental

Arm Description

Stereotactic body radiation therapy (SBRT)

Intervention Type

Radiation

Intervention Name(s)

SBRT

Other Intervention Name(s)

Stereotactic body radiation therapy, Stereotactic ablative radiotherapy, SABR

Intervention Description

SBRT delivered in 3 fractions of 20 Gy/fraction over 1.5 to 2 weeks for a total of 60 Gy

Primary Outcome Measure Information:

Title

Primary Tumor Control at 2 Years

Description

Time Frame

From start of treatment to 2 years.

Secondary Outcome Measure Information:

Title

Rate of Treatment-related Grade 3 or 4 Toxicity

Description

Time Frame

From start of treatment to end of follow-up. Analysis can occur at or after time of primary outcome measure analysis.

Title

Other Grade 3-5 Adverse Events

Description

Time Frame

From start of treatment to end of follow-up. Analysis can occur at or after time of primary outcome measure analysis.

Title

Primary Tumor Failure (PTF), Marginal Failure (MF), Regional Failure (RF), Metastatic Dissemination (MD), Disease-free Survival (DFS), and Overall Survival (OS) at 2 Years

Description

Time Frame

From start of treatment to 2 years.

Title

Level of Comorbidity Burden on Morbidity and Efficacy

Time Frame

From start of treatment to end of follow-up.

Title

Assessment of Predictive Value of Blood Markers for Primary Tumor Control at 2 Years and Treatment-related Adverse Events ≥ Grade 2

Description

Time Frame

From start of treatment to 2 years.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer, including any of the following primary tumor types: Squamous cell carcinoma Adenocarcinoma Large cell carcinoma Large cell neuroendocrine tumor Non-small cell carcinoma not otherwise specified No pure type bronchoalveolar cell carcinoma Stage I or II disease based on 1 of the following combinations of primary tumor, regional nodes, metastasis (TNM) staging: T1, N0, M0 T2 (≤ 5 cm), N0, M0 T3 (≤ 5 cm), N0, M0 (chest wall primary tumors only) No T2 or T3 primary tumors > 5 cm or T3 primary tumors involving the central chest and structures of the mediastinum No primary tumor of any T-stage within or touching the zone of the proximal bronchial tree, defined as a volume of 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, or right and left lower lobe bronchi) Patients with hilar or mediastinal lymph nodes ≤ 1 cm AND no abnormal hilar or mediastinal uptake on positron emission tomography (PET) scan will be considered N0 Patients with > 1 cm hilar or mediastinal lymph nodes on CT scan OR abnormal PET scan (including suspicious but nondiagnostic uptake) will still be eligible if directed tissue biopsies of all abnormally identified areas are negative for cancer No direct evidence of regional or distant metastases after appropriate staging studies Considered a reasonable candidate for surgical resection of the primary tumor, according to the following criteria: Primary tumor predicted to be technically resectable with a high likelihood of negative surgical margins (as determined by a qualified thoracic surgeon) Baseline forced expiratory volume (FEV)_1 > 35% predicted Postoperative predicted FEV_1 > 30% predicted Diffusion capacity > 35% predicted No hypoxemia (e.g., partial pressure of arterial oxygen (PaO2) of ≤ 60 mm Hg) and/or hypercapnia (e.g., partial pressure of arterial carbon dioxide (PaCO2) > 50 mm Hg) at baseline No severe pulmonary hypertension No severe cerebral, cardiac, or peripheral vascular disease No severe chronic heart disease Pleural effusion, if present, must be deemed too small to tap under CT scan guidance and must not be evident on chest x-ray Pleural effusion that appears on chest x-ray will be allowed only after thoracotomy or other invasive procedure PATIENT CHARACTERISTICS: Zubrod performance status 0-1 Absolute neutrophil count ≥ 1,800/mm³ Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 8.0 g/dL (transfusion allowed) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No synchronous primary or other invasive malignancy within the past 3 years other than nonmelanoma skin cancer or in situ cancer No active systemic, pulmonary, or pericardial infection No weight loss > 5% for any reason within the past 3 months PRIOR CONCURRENT THERAPY: No prior radiotherapy for lung cancer Prior radiotherapy as part of treatment for head and neck cancer, breast cancer, or other non-lung cancer is allowed provided there will not be significant overlap with the stereotactic body radiotherapy fields No prior chemotherapy or surgical resection for this lung cancer No other concurrent local or regional antineoplastic therapy (including standard fractionated radiotherapy, non-approved systemic therapy, and surgery), except at disease progression

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Robert D. Timmerman, MD

Organizational Affiliation

Simmons Cancer Center

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Elizabeth M. Gore, MD

Organizational Affiliation

Medical College of Wisconsin

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Harvey I. Pass, MD

Organizational Affiliation

NYU Langone Health

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Martin J. Edelman, MD

Organizational Affiliation

University of Maryland Greenebaum Cancer Center

Official's Role

Study Chair

Facility Information:

Facility Name

UAB Comprehensive Cancer Center

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35294

Country

United States

Facility Name

Alta Bates Summit Comprehensive Cancer Center

City

Berkeley

State/Province

California

ZIP/Postal Code

94704

Country

United States

Facility Name

Mercy Cancer Center at Mercy San Juan Medical Center

City

Carmichael

State/Province

California

ZIP/Postal Code

95608

Country

United States

Facility Name

Marin Cancer Institute at Marin General Hospital

City

Greenbrae

State/Province

California

ZIP/Postal Code

94904

Country

United States

Facility Name

University of California Davis Cancer Center

City

Sacramento

State/Province

California

ZIP/Postal Code

95817

Country

United States

Facility Name

Memorial Hospital of South Bend

City

South Bend

State/Province

Indiana

ZIP/Postal Code

46601

Country

United States

Facility Name

Lucille P. Markey Cancer Center at University of Kentucky

City

Lexington

State/Province

Kentucky

ZIP/Postal Code

40536-0093

Country

United States

Facility Name

Greenebaum Cancer Center at University of Maryland Medical Center

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21201

Country

United States

Facility Name

Lacks Cancer Center at Saint Mary's Health Care

City

Grand Rapids

State/Province

Michigan

ZIP/Postal Code

49503

Country

United States

Facility Name

William Beaumont Hospital - Royal Oak Campus

City

Royal Oak

State/Province

Michigan

ZIP/Postal Code

48073

Country

United States

Facility Name

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

NYU Cancer Institute at New York University Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10016

Country

United States

Facility Name

Stony Brook University Cancer Center

City

Stony Brook

State/Province

New York

ZIP/Postal Code

11794-9446

Country

United States

Facility Name

Wake Forest University Comprehensive Cancer Center

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27157-1096

Country

United States

Facility Name

Penn State Cancer Institute at Milton S. Hershey Medical Center

City

Hershey

State/Province

Pennsylvania

ZIP/Postal Code

17033-0850

Country

United States

Facility Name

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390

Country

United States

Facility Name

INOVA Alexandria Hospital

City

Alexandria

State/Province

Virginia

ZIP/Postal Code

22304

Country

United States

Facility Name

St. Joseph Cancer Center

City

Bellingham

State/Province

Washington

ZIP/Postal Code

98225

Country

United States

Facility Name

Medical College of Wisconsin Cancer Center

City

Milwaukee

State/Province

Wisconsin

ZIP/Postal Code

53226

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

29852037

Citation

Timmerman RD, Paulus R, Pass HI, Gore EM, Edelman MJ, Galvin J, Straube WL, Nedzi LA, McGarry RC, Robinson CG, Schiff PB, Chang G, Loo BW Jr, Bradley JD, Choy H. Stereotactic Body Radiation Therapy for Operable Early-Stage Lung Cancer: Findings From the NRG Oncology RTOG 0618 Trial. JAMA Oncol. 2018 Sep 1;4(9):1263-1266. doi: 10.1001/jamaoncol.2018.1251.

Results Reference

derived

Links:

URL

http://meetinglibrary.asco.org/content/111599-132

Description

RTOG 0618 ASCO 2013 abstract

Learn more about this trial

Stereotactic Body Radiation Therapy in Treating Patients With Stage I or Stage II Non-Small Cell Lung Cancer That Can Be Removed By Surgery

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