Surgery With or Without Internal Radiation Therapy Compared With Stereotactic Body Radiation Therapy in Treating Patients With High-Risk Stage I Non-Small Cell Lung Cancer

NCT ID: NCT01336894

Last Updated: 2017-05-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2017-03-27

Brief Summary

RATIONALE: Surgery with or without internal radiation therapy may be an effective treatment for non-small cell lung cancer. Internal radiation uses radioactive material placed directly into or near a tumor to kill tumor cells. Stereotactic body radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue. It is not yet known whether stereotactic body radiation therapy is more effective than surgery with or without internal radiation therapy in treating non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying how well surgery with or without internal radiation therapy works compared with stereotactic body radiation therapy in treating patients with high-risk stage IA or stage IB non-small cell lung cancer.

Detailed Description

OBJECTIVES:

Primary

• To ascertain whether patients treated by stereotactic body radiation therapy (SBRT) have a 3-year overall survival (OS) rate that is no more than 10% less than patients treated with sublobar resection (SR).

Secondary

• To compare loco-regional recurrence-free survival between study arms.
• To compare disease-free survival between study arms.
• To compare grade 3 or higher specific adverse event profiles between study arms at 1, 3, 6, and 12 months post-therapy.
• To compare pulmonary function between patients treated with SBRT and patients treated with SR.
• To compare the adverse events and pulmonary function tests (PFTs) in each arm for patients with low or high Charlson comorbidity index scores, including a test interaction between Charlson comorbidity index scores (low vs high) and treatment arm.

Tertiary

• To compare the quality-adjusted survival between the SBRT and SR treatments in terms of time to death (primary) and time until recurrence (secondary).
• To examine whether pre-operative and post-operative clinically significant deficits in previously identified prognostic PRO domains (overall quality of life [QOL], fatigue, anxiety, and dyspnea) are associated with shorter patient survival in this patient population and to compare the relative effectiveness of each treatment (SBRT and SR).
• To contribute to an ACOSOG bank of normative data in order to improve short/long-term outcomes of cancer patients by identifying patients experiencing clinically significant deficits in patient-reported outcomes and the relationship to genetic variables.
• To explore whether blood-based biomarkers, including osteopontins, will be able to predict which patients will be at high risk for recurrence by treatment with either SBRT or SR. (exploratory)
• To explore whether blood-based biomarkers, including TGF-β1, will be able to predict which patients will be at high risk for pulmonary complications by treatment with either SBRT or SR. (exploratory)

OUTLINE: This is a multicenter study. Patients are stratified according to planned brachytherapy (yes vs no) and ECOG performance status (0 vs 1 vs 2). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo sublobar resection comprising either a wedge resection or anatomical segmentectomy with or without intraoperative brachytherapy* comprising an iodine I 125 implant at the resection margin.
• Arm II: Patients undergo 3 fractions of stereotactic body radiation therapy at 2-8 days apart.

NOTE: *Patients may receive brachytherapy at the discretion of treating physician.

Patients may undergo blood sample collection at baseline and periodically during study for correlative studies. Tumor tissue samples may also be collected from patients who undergo resection.

Patients complete the Lung Cancer Symptom Scale (LCSS), the Linear Analogue Self-Assessment (LASA), and the UCDS Shortness of Breath quality-of-life questionnaires at baseline and periodically during study and follow-up.

After completion of study treatment, patients are followed up for 30 days, every 3 months for 2 years, every 6 months for 1 year, and then yearly for 2 years.

Conditions

Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I (SR+Brachytherapy)

Patients undergo sublobar resection comprising either a wedge resection or anatomical segmentectomy with or without intraoperative brachytherapy comprising an iodine I 125 implant at the resection margin.

Group Type: ACTIVE_COMPARATOR

therapeutic conventional surgery

Intervention Type: PROCEDURE

Undergo surgery

iodine I 125

Intervention Type: RADIATION

Undergo seed implant radiotherapy

Arm II (SBRT)

Patients undergo 3 fractions of stereotactic body radiation therapy at 2-8 days apart.

Group Type: EXPERIMENTAL

stereotactic body radiation therapy

Intervention Type: RADIATION

Undergo radiotherapy

Interventions

therapeutic conventional surgery

Undergo surgery

Intervention Type: PROCEDURE

iodine I 125

Undergo seed implant radiotherapy

Intervention Type: RADIATION

stereotactic body radiation therapy

Undergo radiotherapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• No evidence of distant metastases

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0, 1, or 2
• Patient at high-risk for surgery by meeting a minimum of one major criteria or two minor criteria as described below:

• Major criteria

• FEV1 ≤ 50% predicted
• DLCO ≤ 50% predicted
• Minor criteria

• Age ≥ 75 years
• FEV1 51-60% predicted
• DLCO 51-60% predicted
• Pulmonary hypertension (defined as a pulmonary artery systolic pressure greater than 40 mm Hg) as estimated by echocardiography or right heart catheterization
• Poor left ventricular function (defined as an ejection fraction of 40% or less)
• Resting or exercise arterial pO2 ≤ 55 mm Hg or SpO2 ≤ 88%
• pCO2 > 45 mm Hg
• Modified Medical Research Council (MMRC) Dyspnea Scale ≥ 3
• Not pregnant or nursing
• Negative urine or serum pregnancy test
• Fertile patients must use effective contraception
• No prior invasive malignancy, unless disease-free for ≥ 3 years prior to registration (except non-melanoma skin cancer, in-situ cancers).

PRIOR CONCURRENT THERAPY:

• No prior intra-thoracic radiotherapy

• Prior radiotherapy as part of treatment for head and neck, breast, or other non-thoracic cancer is permitted
• Prior chemotherapy or surgical resection for the lung cancer being treated on this protocol is NOT permitted

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hiran C. Fernando, MD

Role: PRINCIPAL_INVESTIGATOR

Boston Medical Center

Locations

UAB Comprehensive Cancer Center

Birmingham, Alabama, United States

Mayo Clinic Hospital

Phoenix, Arizona, United States

Mayo Clinic Scottsdale

Scottsdale, Arizona, United States

University of California Davis Cancer Center

Sacramento, California, United States

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Stanford Cancer Center

Stanford, California, United States

Baptist Cancer Institute - Jacksonville

Jacksonville, Florida, United States

M.D. Anderson Cancer Center at Orlando

Orlando, Florida, United States

Emory Crawford Long Hospital

Atlanta, Georgia, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center

Savannah, Georgia, United States

University of Chicago Cancer Research Center

Chicago, Illinois, United States

OSF St. Francis Medical Center

Peoria, Illinois, United States

Lucille P. Markey Cancer Center at University of Kentucky

Lexington, Kentucky, United States

James Graham Brown Cancer Center at University of Louisville

Louisville, Kentucky, United States

DeCesaris Cancer Institute at Anne Arundel Medical Center

Annapolis, Maryland, United States

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States

St. Agnes Hospital Cancer Center

Baltimore, Maryland, United States

Tufts Medical Center Cancer Center

Boston, Massachusetts, United States

Boston University Cancer Research Center

Boston, Massachusetts, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

William Beaumont Hospital - Royal Oak Campus

Royal Oak, Michigan, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, United States

Valley Hospital - Ridgewood

Ridgewood, New Jersey, United States

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

New York, New York, United States

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

Rochester, New York, United States

Stony Brook University Cancer Center

Stony Brook, New York, United States

SUNY Upstate Medical University Hospital

Syracuse, New York, United States

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Charles M. Barrett Cancer Center at University Hospital

Cincinnati, Ohio, United States

Cleveland Clinic Taussig 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

Providence Cancer Center at Providence Portland Medical Center

Portland, Oregon, United States

Geisinger Cancer Institute at Geisinger Health

Danville, Pennsylvania, United States

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

Philadelphia, Pennsylvania, United States

Allegheny Cancer Center at Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

York Cancer Center at Apple Hill Medical Center

York, Pennsylvania, United States

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States

Baylor University Medical Center - Dallas

Dallas, Texas, United States

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

Dallas, Texas, United States

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Sentara Cancer Institute at Sentara Norfolk General Hospital

Norfolk, Virginia, United States

Providence Regional Cancer Partnership

Everett, Washington, United States

Swedish Cancer Institute at Swedish Medical Center - First Hill Campus

Seattle, Washington, United States

Gundersen Lutheran Center for Cancer and Blood

La Crosse, Wisconsin, United States

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, United States

Veterans Affairs Medical Center - Milwaukee

Milwaukee, Wisconsin, United States

Waukesha Memorial Hospital Regional Cancer Center

Waukesha, Wisconsin, United States

London Regional Cancer Program at London Health Sciences Centre

London, Ontario, Canada

Ottawa Hospital Regional Cancer Centre - General Campus

Ottawa, Ontario, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

Hopital Notre-Dame du CHUM

Montreal, Quebec, Canada

Countries

United States; Canada

References

Fernando HC, Timmerman R. American College of Surgeons Oncology Group Z4099/Radiation Therapy Oncology Group 1021: a randomized study of sublobar resection compared with stereotactic body radiotherapy for high-risk stage I non-small cell lung cancer. J Thorac Cardiovasc Surg. 2012 Sep;144(3):S35-8. doi: 10.1016/j.jtcvs.2012.06.003. Epub 2012 Jul 11.

Reference Type: RESULT

PMID: 22795435 (View on PubMed)

Other Identifiers

U10CA076001

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-02667

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000698986

Identifier Type: REGISTRY

Identifier Source: secondary_id

Z4099

Identifier Type: -

Identifier Source: org_study_id