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

Phase 1
Completed
Conditions
Lung Cancer
Interventions
Radiation: SBRT 42.5 Gy
Radiation: SBRT 40.0 Gy
Radiation: SBRT 50.0 Gy
Radiation: SBRT 45.0 Gy
Radiation: SBRT 55.0 Gy
Radiation: SBRT 60.0 Gy
Radiation: SBRT 47.5 Gy
Radiation: SBRT 52.5 Gy
Radiation: SBRT 57.5 Gy
Registration Number
NCT00750269
Lead Sponsor
Radiation Therapy Oncology Group
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.

PURPOSE: This phase I/II trial is studying the side effects and best dose of stereotactic body radiation therapy and to see how well it works in treating patients with stage I non-small cell lung cancer.

Detailed Description

OBJECTIVES:

Primary

* To determine the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) in medically inoperable patients with centrally located stage I non-small cell lung cancer. (Phase I)

* To estimate the local control rate of SBRT at the MTD in these patients. (Phase II)

Secondary

* To estimate the rates of adverse events (other than dose-limiting toxicity) of ≥ grade 3 that is possibly, probably, or definitely related to treatment and that occurs within 1 year after the start of SBRT in these patients.

* To estimate the rates of late adverse events (i.e., occurs \> 1 year after the start of SBRT) in these patients.

* To estimate the local control and progression-free and overall survival rates in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients undergo stereotactic body radiotherapy every 2 days over 1½-2 weeks \[total of 5 fractions (FX)\] in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 3 months for 2 years, then every 6 months for 2 years, then annually.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
120
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Level 2: 8.5 Gy/FXSBRT 42.5 GySBRT 42.5 Gy
Level 1: 8.0 Gy/FXSBRT 40.0 GySBRT 40.0 Gy
Level 5: 10.0 Gy/FXSBRT 50.0 GySBRT 50.0 Gy
Level 3: 9.0 Gy/FXSBRT 45.0 GySBRT 45.0 Gy
Level 7: 11.0 Gy/FXSBRT 55.0 GySBRT 55.0 Gy
Level 9: 12.0 Gy/FXSBRT 60.0 GySBRT 60.0 Gy
Level 4: 9.5 Gy/FXSBRT 47.5 GySBRT 47.5 Gy
Level 6: 10.5 Gy/FXSBRT 52.5 GySBRT 52.5 Gy
Level 8: 11.5 Gy/FXSBRT 57.5 GySBRT 57.5 Gy
Primary Outcome Measures
NameTimeMethod
(Phase II) Primary Tumor Control Rate at the Maximum Tolerated Dose (MTD)From start of SBRT to 2 years.

Primary tumor control is defined as the absence of primary tumor failure. Primary tumor failure (PTF) refers to the primary treated tumor after protocol therapy and corresponds to meeting following two criteria: 1) Increase in tumor dimension of 20% as defined above for local enlargement (LE); 2) The measurable tumor with criteria meeting LE should be avid on Positron Emission Tomography (PET) imaging with uptake of a similar intensity as the pretreatment staging PET, OR the measurable tumor should be biopsied confirming viable carcinoma. Marginal Failures (MF) and Involved Lobe Failures were also counted as PTF. The cumulative incidence method was used to estimate primary tumor control rate. The 90% confidence interval for local control was calculated using bootstrapping methods. Per the protocol, only the MTD dose level was to be analyzed. However, due to the quantity of patients enrolled on Dose Level 8 as well as safety concerns, Dose Level 8 was analyzed also.

(Phase I) Maximum Tolerated Dose of Stereotactic Body Radiotherapy (SBRT) as Assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0From start of SBRT to 1 year

Maximum tolerated dose (MTD) defined as dose most closely associated with a 20% probability of experiencing a toxicity \<= 1 year from start of SBRT from following dose-limiting toxicities: Gr 3-5 Cardiac: Pericardial effusion, Pericarditis, Restrictive cardiomyopathy; Gr 4-5 GI: Dysphagia, Esophagitis, Esophageal fistula/obstruction/perforation/stenosis/ulcer/hemorrhage; Gr 3-5 Nervous System Disorders: Brachial plexopathy, Recurrent laryngeal nerve palsy, Myelitis; Gr 3-5 Respiratory: Atelectasis (gr 4-5 only), Bronchopulmonary/mediastinal/pleural/tracheal hemorrhage, Bronchial/pulmonary/bronchopleural/tracheal fistula, Hypoxia (provided gr 3 is worse than baseline), Bronchial/tracheal obstruction, Pleural effusion, Pneumonitis, Pulmonary fibrosis; Changes in Pulmonary Function Tests per SBRT Pulmonary Toxicity Scale, Gr 3-5: FEV1 decline, FVC decline; Any Gr 5 adverse event attributed to treatment. Dose level was determined by time-to-event continual reassessment method (TITE-CRM).

Secondary Outcome Measures
NameTimeMethod
Rate of Toxicity ≥ Grade 3 (Other Than DLT) Within One Year as Assessed by NCI CTCAE v4.0From start of SBRT until 1 year.

Rate of patients developing any treatment-related toxicity during the first year following the start of SBRT that is not among the types considered as a dose-limiting toxicity.

Progression-free SurvivalFrom randomization to date of death, failure (local, regional or distant) or last follow-up. Analysis occurs after all patients have been potentially followed for 24 months, approximately 7.5 years from the start of the study.

Progression-free survival is defined as the state of being alive without progression of disease. A failure is the first of the following: local progression, regional progression, distant metastasis, or death. Progression-free survival was assessed at the maximum tolerated dose using the Kaplan-Meier method to estimate the 2-year survival rate. Arms were not compared/tested.

Overall SurvivalFrom randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 24 months, approximately 7.5 years from the start of the study.

An event for overall survival is death due to any cause. Overall survival was assessed at the maximum tolerated dose using the Kaplan-Meier method to estimate the 2-year survival rate. Arms were not compared/tested.

Rate of Late Toxicity (i.e., Occurs > 1 Year After the Start of SBRT) of ≥ Grade 3 as Assessed by NCI CTCAE v4.0From start of treatment to end of follow-up. Analysis occurs after all patients have been potentially followed for 24 months, approximately 7.5 years from the start of the study.

Percentage of patients who developed any treatment-related toxicity after the first year following the start of SBRT.

Nodal ProgressionFrom randomization to date of death, regional failure or last follow-up. Analysis occurs after all patients have been potentially followed for 24 months, approximately 7.5 years from the start of the study.

Regional nodal progression is defined as appearance after protocol therapy 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. Regional nodal progression was assessed using the cumulative incidence method to estimate the 2-year failure rate. Arms were not compared/tested.

Local ProgressionFrom randomization to date of death, regional failure or last follow-up. Analysis occurs after all patients have been potentially followed for 24 months.

Local progression is the same as primary tumor failure (PTF) which refers to the primary treated tumor after protocol therapy and corresponds to meeting both of the following two criteria: 1) Increase in tumor dimension of 20% as defined above for local enlargement (LE); 2) The measurable tumor with criteria meeting LE should be avid on Positron Emission Tomography (PET) imaging with uptake of a similar intensity as the pretreatment staging PET, OR the measurable tumor should be biopsied confirming viable carcinoma. For outcome analysis, Marginal Failures (MF) and Involved Lobe Failures will also be counted as PTF. Local progression was assessed using the cumulative incidence method to estimate the 2-year failure rate. Arms were not compared/tested.

Distant MetastasesFrom randomization to date of death, distant failure or last follow-up. Analysis occurs after all patients have been potentially followed for 24 months, approximately 7.5 years from the start of the study.

Distant metastases is defined as the appearance after protocol therapy of cancer deposits characteristic of metastatic dissemination from non-small cell lung cancer. Distant metastases progression was assessed using the cumulative incidence method to estimate the 2-year failure rate. Arms were not compared/tested.

Trial Locations

Locations (58)

CCOP - Mount Sinai Medical Center

🇺🇸

Miami Beach, Florida, United States

Norton Suburban Hospital

🇺🇸

Louisville, Kentucky, United States

Radiation Oncology Centers - Cameron Park

🇺🇸

Cameron Park, California, United States

University of California Davis Cancer Center

🇺🇸

Sacramento, California, United States

CCOP - Kansas City

🇺🇸

Prairie Village, Kansas, United States

Lacks Cancer Center at Saint Mary's Health Care

🇺🇸

Grand Rapids, Michigan, United States

James P. Wilmot Cancer Center at University of Rochester Medical Center

🇺🇸

Rochester, New York, United States

Cooper CyberKnife Center

🇺🇸

Mount Laurel, New Jersey, United States

Josephine Ford Cancer Center at Henry Ford Hospital

🇺🇸

Detroit, Michigan, United States

Mercy and Unity Cancer Center at Unity Hospital

🇺🇸

Fridley, Minnesota, United States

M.D. Anderson Cancer Center at Orlando

🇺🇸

Orlando, Florida, United States

Arizona Center for Cancer Care - Peoria

🇺🇸

Peoria, Arizona, United States

Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center

🇺🇸

Los Angeles, California, United States

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

🇺🇸

Lebanon, New Hampshire, United States

Summa Center for Cancer Care at Akron City Hospital

🇺🇸

Akron, Ohio, United States

Frederick R. and Betty M. Smith Cancer Treatment Center

🇺🇸

Sparta, New Jersey, United States

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

🇺🇸

New York, New York, United States

Tulane Cancer Center Office of Clinical Research

🇺🇸

Alexandria, Louisiana, United States

Butterworth Hospital at Spectrum Health

🇺🇸

Grand Rapids, Michigan, United States

Maine Center for Cancer Medicine and Blood Disorders - Scarborough

🇺🇸

Scarborough, Maine, United States

Mercy and Unity Cancer Center at Mercy Hospital

🇺🇸

Coon Rapids, Minnesota, United States

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

🇺🇸

Dallas, Texas, United States

Roswell Park Cancer Institute

🇺🇸

Buffalo, New York, United States

Regions Hospital Cancer Care Center

🇺🇸

Saint Paul, Minnesota, United States

St. Luke's - Roosevelt Hospital Center - St.Luke's Division

🇺🇸

New York, New York, United States

Rosenfeld Cancer Center at Abington Memorial Hospital

🇺🇸

Abington, Pennsylvania, United States

William Beaumont Hospital - Royal Oak Campus

🇺🇸

Royal Oak, Michigan, United States

Albert Einstein Cancer Center

🇺🇸

Philadelphia, Pennsylvania, United States

Wake Forest University Comprehensive Cancer Center

🇺🇸

Winston-Salem, North Carolina, United States

Medical College of Wisconsin Cancer Center

🇺🇸

Milwaukee, Wisconsin, United States

Lankenau Cancer Center at Lankenau Hospital

🇺🇸

Wynnewood, Pennsylvania, United States

Frankford Hospital Cancer Center - Torresdale Campus

🇺🇸

Philadelphia, Pennsylvania, United States

Flower Hospital Cancer Center

🇺🇸

Sylvania, Ohio, United States

Veterans Affairs Medical Center - Milwaukee

🇺🇸

Milwaukee, Wisconsin, United States

Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center

🇺🇸

Hershey, Pennsylvania, United States

Greenebaum Cancer Center at University of Maryland Medical Center

🇺🇸

Baltimore, Maryland, United States

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

🇺🇸

Columbus, Ohio, United States

Case Comprehensive Cancer Center

🇺🇸

Cleveland, Ohio, United States

University Cancer Center at University of Washington Medical Center

🇺🇸

Seattle, Washington, United States

Mayo Clinic Scottsdale

🇺🇸

Scottsdale, Arizona, United States

Roy and Patricia Disney Family Cancer Center at Providence Saint Joseph Medical Center

🇺🇸

Burbank, California, United States

Mercy Cancer Center at Mercy San Juan Medical Center

🇺🇸

Carmichael, California, United States

CCOP - Christiana Care Health Services

🇺🇸

Newark, Delaware, United States

Baptist Cancer Institute - Jacksonville

🇺🇸

Jacksonville, Florida, United States

George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus

🇺🇸

New Britain, Connecticut, United States

Lucille P. Markey Cancer Center at University of Kentucky

🇺🇸

Lexington, Kentucky, United States

OSF St. Francis Medical Center

🇺🇸

Peoria, Illinois, United States

McLaren Cancer Institute

🇺🇸

Flint, Michigan, United States

Saint Louis University Cancer Center

🇺🇸

Saint Louis, Missouri, United States

Mayo Clinic Cancer Center

🇺🇸

Rochester, Minnesota, United States

Dale and Frances Hughes Cancer Center at Pocono Medical Center

🇺🇸

East Stroudsburg, Pennsylvania, United States

McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center

🇺🇸

Reading, Pennsylvania, United States

Sentara Cancer Institute at Sentara Norfolk General Hospital

🇺🇸

Norfolk, Virginia, United States

St. Joseph Cancer Center

🇺🇸

Bellingham, Washington, United States

Charles M. Barrett Cancer Center at University Hospital

🇺🇸

Cincinnati, Ohio, United States

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

🇺🇸

Minneapolis, Minnesota, United States

UCSF Helen Diller Family Comprehensive Cancer Center

🇺🇸

San Francisco, California, United States

Princess Margaret Hospital

🇨🇦

Toronto, Ontario, Canada

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