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

Lung Cancer Clinical Trial

Official title:

A Randomized Phase III Study of Sublobar Resection (+/- Brachytherapy) Versus Stereotactic Body Radiation Therapy in High Risk Patients With Stage I Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01336894
• Other study ID #: Z4099
• Secondary ID: U10CA076001NCI-2
• Status: Terminated
• Phase: Phase 3
• First received: April 15, 2011
• Last updated: August 11, 2016
• Start date: May 2011

Study information

• Verified date: August 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Central Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Lung nodule suspicious for non-small cell lung cancer (NSCLC)

• Biopsy confirmation is strongly recommended but not required; if biopsy is attempted and non-diagnostic, if the patient refuses biopsy, or if the risk of biopsy is considered too high, patients may be enrolled if the mass is suspicious for NSCLC based on two or more of the following criteria:

• Positive smoking history

• Absence of benign calcifications within suspicious nodule

• Activity on PET greater than normal tissue

• Evidence of growth compared to previous imaging

• Presence of spiculation

• Tumor = 4 cm maximum diameter, clinical stage IA or selected IB (i.e., with visceral pleural involvement) by PET/CT scan of the chest and upper abdomen performed within 60 days prior to registration

• All clinically suspicious mediastinal N1, N2, or N3 lymph nodes (> 1 cm short-axis dimension on CT scan and/or positive on PET scan) confirmed negative for involvement with NSCLC by one of the following methods: mediastinoscopy, anterior mediastinotomy, endoscopic and/or endobronchial ultrasonography (EUS/EBUS)-guided needle aspiration, CT-guided, or video-assisted thoracoscopic or open lymph node biopsy

• Tumor verified by a thoracic surgeon to be in a location that will permit sublobar resection

• Tumor located peripherally within the lung, defined as not touching any surface within 2 cm of the proximal bronchial tree in all directions

• Patients with non-peripheral (central) tumors are NOT eligible

• 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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Procedure:
• therapeutic conventional surgery
Undergo surgery

Radiation:
• iodine I 125
Undergo seed implant radiotherapy
• stereotactic body radiation therapy
Undergo radiotherapy

Locations

Country	Name	City	State
Canada	London Regional Cancer Program at London Health Sciences Centre	London	Ontario
Canada	Hopital Notre-Dame du CHUM	Montreal	Quebec
Canada	Ottawa Hospital Regional Cancer Centre - General Campus	Ottawa	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	DeCesaris Cancer Institute at Anne Arundel Medical Center	Annapolis	Maryland
United States	Emory Crawford Long Hospital	Atlanta	Georgia
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	St. Agnes Hospital Cancer Center	Baltimore	Maryland
United States	UAB Comprehensive Cancer Center	Birmingham	Alabama
United States	Boston University Cancer Research Center	Boston	Massachusetts
United States	Tufts Medical Center Cancer Center	Boston	Massachusetts
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	University of Chicago Cancer Research Center	Chicago	Illinois
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	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	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida
United States	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin
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	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Veterans Affairs Medical Center - Milwaukee	Milwaukee	Wisconsin
United States	St. Luke's - Roosevelt Hospital Center - St.Luke's Division	New York	New York
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	OSF St. Francis Medical Center	Peoria	Illinois
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	Mayo Clinic Hospital	Phoeniz	Arizona
United States	Allegheny Cancer Center at Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	Valley Hospital - Ridgewood	Ridgewood	New Jersey
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	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	Stanford Cancer Center	Stanford	California
United States	Stony Brook University Cancer Center	Stony Brook	New York
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	Waukesha Memorial Hospital Regional Cancer Center	Waukesha	Wisconsin
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina
United States	York Cancer Center at Apple Hill Medical Center	York	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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 Th — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	5-year OS rate		Up to 5 years post-randomization	No
Secondary	Loco-regional recurrence-free survival		Up to 5 years post-randomization	No
Secondary	Adverse event profiles at 1, 3, 6, and 12 months post-therapy		Up to 12 months post-therapy	Yes
Secondary	Disease-free survival		Up to 5 years post-randomization	No
Secondary	Pulmonary function test values		Up to 12 months post-therapy	Yes