Clinical trial NCT01336894: 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
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Lung Cancer
Keywords: stage IA non-small cell lung cancer
stage IB non-small cell lung cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2011-04-18
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 3-year Overall Survival (OS) Rate
timeFrame: Up to 3 years post-randomization
Secondary outcomes:
measure: Loco-regional Recurrence-free Survival
timeFrame: Up to 5 years post-randomization
measure: Adverse Event Profiles at 1 Month Post-therapy
timeFrame: 1 month post-therapy
measure: Adverse Event Profiles at 3 Months Post-therapy
timeFrame: 3 months post-therapy
measure: Adverse Event Profiles at 12 Months Post-therapy
timeFrame: 12 months post-therapy
measure: Disease-free Survival
timeFrame: Up to 5 years post-randomization
measure: Pulmonary Function Test Values
timeFrame: Up to 12 months post-therapy
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Comprehensive Cancer Center
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Jacksonville
country: United States
facility: Baptist Cancer Institute - Jacksonville
state: Florida
city: Orlando
country: United States
facility: M.D. Anderson Cancer Center at Orlando
state: Florida
city: Atlanta
country: United States
facility: Emory Crawford Long Hospital
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Savannah
country: United States
facility: Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Peoria
country: United States
facility: OSF St. Francis Medical Center
state: Illinois
city: Lexington
country: United States
facility: Lucille P. Markey Cancer Center at University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: James Graham Brown Cancer Center at University of Louisville
state: Kentucky
city: Annapolis
country: United States
facility: DeCesaris Cancer Institute at Anne Arundel Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: St. Agnes Hospital Cancer Center
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Boston University Cancer Research Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital - Royal Oak Campus
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Ridgewood
country: United States
facility: Valley Hospital - Ridgewood
state: New Jersey
city: New York
country: United States
facility: St. Luke's - Roosevelt Hospital Center - St.Luke's Division
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Cancer Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
state: Ohio
city: Portland
country: United States
facility: Providence Cancer Center at Providence Portland Medical Center
state: Oregon
city: Danville
country: United States
facility: Geisinger Cancer Institute at Geisinger Health
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Cancer Center at Allegheny General Hospital
state: Pennsylvania
city: York
country: United States
facility: York Cancer Center at Apple Hill Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Baylor University Medical Center - Dallas
state: Texas
city: Dallas
country: United States
facility: Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Norfolk
country: United States
facility: Sentara Cancer Institute at Sentara Norfolk General Hospital
state: Virginia
city: Everett
country: United States
facility: Providence Regional Cancer Partnership
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
state: Washington
city: La Crosse
country: United States
facility: Gundersen Lutheran Center for Cancer and Blood
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Veterans Affairs Medical Center - Milwaukee
state: Wisconsin
city: Waukesha
country: United States
facility: Waukesha Memorial Hospital Regional Cancer Center
state: Wisconsin
city: London
country: Canada
facility: London Regional Cancer Program at London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Regional Cancer Centre - General Campus
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Hopital Notre-Dame du CHUM
state: Quebec
Study officials:
affiliation: Boston Medical Center
name: Hiran C. Fernando, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.