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

Lung Cancer Clinical Trial

Official title:

Seamless Phase I/II Study of Stereotactic Lung Radiotherapy (SBRT) for Early Stage, Centrally Located, Non-Small Cell Lung Cancer (NSCLC) in Medically Inoperable Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00750269
• Other study ID #: RTOG-0813
• Secondary ID: CDR0000613524NCI
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 2009
• Est. completion date: May 20, 2022

Study information

• Verified date: May 2022
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT01317056

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: May 20, 2022
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

• Stage T1-2, N0, M0 disease

• Tumor size = 5 cm

• Tumor must be 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 (i.e., 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) OR immediately adjacent to the mediastinal or pericardial pleura (PTV touching the pleura)

• Hilar or mediastinal lymph nodes = 1 cm AND no abnormal hilar or mediastinal uptake on positron emission tomography (PET) scan are considered N0

• Mediastinal lymph node sampling by any technique is allowed but not required

• Patients with > 1 cm hilar or mediastinal lymph nodes on CT scan or abnormal PET scan (including suspicious but nondiagnostic uptake) are eligible provided directed tissue biopsies of all abnormally identified areas are negative for cancer

• Tumor deemed technically resectable, in the opinion of an experienced thoracic cancer surgeon, with a reasonable possibility of obtaining a gross total resection with negative margins, defined as a potentially curative resection (PCR)

• Patient deemed "medically inoperable" due to severe underlying physiological medical problems that would prohibit a PCR, including any of the following:

• Baseline forced expiratory volume at 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-stage organ damage

• Severe cerebral, cardiac, or peripheral vascular disease

• Severe chronic heart disease

• Measurable disease as documented by CT scan or whole-body PET scan within the past 8 weeks

• Patients with lesions that cannot be visualized by CT scan are not eligible

• Pleural effusion allowed provided it is deemed too small to tap under CT guidance and is not evident on chest x-ray

• Pleural effusion that appears on chest x-ray is allowed only after thoracotomy or other invasive procedure

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2

• Not pregnant

• Negative pregnancy test

• Fertile patients must use effective contraception during and for = 60 days after completion of study therapy

• No other invasive malignancy within the past 2 years except nonmelanomatous skin cancer or carcinoma in situ of the breast, oral cavity, or cervix

• Prior lung cancer allowed provided the patient has been disease-free for = 2 years

PRIOR CONCURRENT THERAPY:

• No prior radiotherapy to the region of the study cancer that would result in overlap of radiotherapy fields

• No prior chemotherapy for the study cancer

• No other concurrent local therapy (including standard-fractionated radiotherapy and/or surgery) or systemic therapy (including standard chemotherapy or biologic targeted agents) specifically intended as treatment for study cancer

• Local or systemic therapy at the time of disease progression allowed

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Radiation:
• SBRT 40.0 Gy
SBRT delivered in 5 fractions of 8.0 Gy/fraction over 1.5 to 2 weeks for a total of 40.0 Gy
• SBRT 42.5 Gy
SBRT delivered in 5 fractions of 8.5 Gy/fraction over 1.5 to 2 weeks for a total of 42.5 Gy
• SBRT 45.0 Gy
SBRT delivered in 5 fractions of 9.0 Gy/fraction over 1.5 to 2 weeks for a total of 45.0 Gy
• SBRT 47.5 Gy
SBRT delivered in 5 fractions of 9.5 Gy/fraction over 1.5 to 2 weeks for a total of 47.5 Gy
• SBRT 50.0 Gy
SBRT delivered in 5 fractions of 10.0 Gy/fraction over 1.5 to 2 weeks for a total of 50.0 Gy
• SBRT 52.5 Gy
SBRT delivered in 5 fractions of 10.5 Gy/fraction over 1.5 to 2 weeks for a total of 52.5 Gy
• SBRT 55.0 Gy
SBRT delivered in 5 fractions of 11.0 Gy/fraction over 1.5 to 2 weeks for a total of 55.0 Gy
• SBRT 57.5 Gy
SBRT delivered in 5 fractions of 11.5 Gy/fraction over 1.5 to 2 weeks for a total of 57.5 Gy
• SBRT 60.0 Gy
SBRT delivered in 5 fractions of 12.0 Gy/fraction over 1.5 to 2 weeks for a total of 60.0 Gy

Locations

Country	Name	City	State
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	Rosenfeld Cancer Center at Abington Memorial Hospital	Abington	Pennsylvania
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	Tulane Cancer Center Office of Clinical Research	Alexandria	Louisiana
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	St. Joseph Cancer Center	Bellingham	Washington
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Roy and Patricia Disney Family Cancer Center at Providence Saint Joseph Medical Center	Burbank	California
United States	Radiation Oncology Centers - Cameron Park	Cameron Park	California
United States	Mercy Cancer Center at Mercy San Juan Medical Center	Carmichael	California
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center	Columbus	Ohio
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	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Dale and Frances Hughes Cancer Center at Pocono Medical Center	East Stroudsburg	Pennsylvania
United States	McLaren Cancer Institute	Flint	Michigan
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
United States	Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky
United States	Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center	Los Angeles	California
United States	Norton Suburban Hospital	Louisville	Kentucky
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Veterans Affairs Medical Center - Milwaukee	Milwaukee	Wisconsin
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Cooper CyberKnife Center	Mount Laurel	New Jersey
United States	George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus	New Britain	Connecticut
United States	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York
United States	St. Luke's - Roosevelt Hospital Center - St.Luke's Division	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Sentara Cancer Institute at Sentara Norfolk General Hospital	Norfolk	Virginia
United States	M.D. Anderson Cancer Center at Orlando	Orlando	Florida
United States	Arizona Center for Cancer Care - Peoria	Peoria	Arizona
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Albert Einstein Cancer Center	Philadelphia	Pennsylvania
United States	Frankford Hospital Cancer Center - Torresdale Campus	Philadelphia	Pennsylvania
United States	CCOP - Kansas City	Prairie Village	Kansas
United States	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan
United States	University of California Davis Cancer Center	Sacramento	California
United States	Saint Louis University Cancer Center	Saint Louis	Missouri
United States	Regions Hospital Cancer Care Center	Saint Paul	Minnesota
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Maine Center for Cancer Medicine and Blood Disorders - Scarborough	Scarborough	Maine
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	Frederick R. and Betty M. Smith Cancer Treatment Center	Sparta	New Jersey
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina
United States	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI), NRG Oncology

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	(Phase I) Maximum Tolerated Dose of Stereotactic Body Radiotherapy (SBRT) as Assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0	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).	From start of SBRT to 1 year
Primary	(Phase II) Primary Tumor Control Rate at the Maximum Tolerated Dose (MTD)	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.	From start of SBRT to 2 years.
Secondary	Progression-free Survival	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.	From 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.
Secondary	Overall Survival	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.	From 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.
Secondary	Local Progression	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.	From randomization to date of death, regional failure or last follow-up. Analysis occurs after all patients have been potentially followed for 24 months.
Secondary	Nodal Progression	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.	From 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.
Secondary	Distant Metastases	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.	From 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.
Secondary	Rate of Toxicity = Grade 3 (Other Than DLT) Within One Year as Assessed by NCI CTCAE v4.0	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.	From start of SBRT until 1 year.
Secondary	Rate of Late Toxicity (i.e., Occurs > 1 Year After the Start of SBRT) of = Grade 3 as Assessed by NCI CTCAE v4.0	Percentage of patients who developed any treatment-related toxicity after the first year following the start of SBRT.	From 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.