Surgery With or Without Internal Radiation Therapy in Treating Patients With Stage I Non-Small Cell Lung Cancer

Phase 3

Completed

Conditions: Lung Cancer

Interventions: Procedure: surgery
Radiation: brachytherapy

Registration Number: NCT00107172

Lead Sponsor: Alliance for Clinical Trials in Oncology

Brief Summary: This randomized phase III trial studies surgery and internal radiation therapy to see how well they work compared to surgery alone in treating patients with stage I non-small cell lung cancer. Surgery 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. It is not yet known whether surgery and internal radiation therapy are more effective than surgery alone in treating non-small cell lung cancer.

Detailed Description: PRIMARY OBJECTIVES:

I. To ascertain whether patients treated by sublobar resection (SR) + brachytherhapy (BX) have longer time to local recurrence as compared to the patients treated by SR (local recurrence includes recurrence within the same lobe or hilum \[N1 nodes\], or progression at the staple line after treatment effects such as scarring have subsided).

SECONDARY OBJECTIVES:

I. To compare procedure specific morbidity and mortality between study arms. II. To compare overall survival and failure-free survival between study arms. III. To assess freedom from regional or distant recurrence. IV. To assess the effect of histological or cytologic positive resection margins on time to local recurrence.

V. To determine the effect of brachytherapy on quality of life (QoL). VI. To determine the effect of brachytherapy on pulmonary function.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo open or thoracoscopic sublobar resection comprising either a wedge resection or anatomical segmentectomy.

ARM II: Patients undergo surgery as in arm I. Patients also undergo intraoperative brachytherapy comprising iodine I 125 implant at the resection margin.

After completion of study treatment, patients are followed at 3, 6, 12, 18, 24, 30, and 36 months and then yearly for 2 years.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 224

Inclusion Criteria

PART I: PRE-OPERATIVE CRITERIA (PRE-REGISTRATION/RANDOMIZATION)
Patients must have a suspicious lung nodule for clinical stage I non-small cell lung cancer (NSCLC)
Patient must have a mass =< 3 cm maximum diameter by computed tomography (CT) size estimate: clinical stage Ia or selected Ib (i.e., with visceral pleural involvement)
Patient must have a CT scan of the chest with upper abdomen within 60 days prior to date of pre-registration
Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status 0, 1, or 2
Patient must meet at least one major criteria or meet a minimum of two minor criteria as described below:
- Major criteria
  - Forced expiratory volume in 1 second (FEV1) =< 50% predicted
  - Diffusing capacity of the lungs for carbon monoxide (DLCO) =< 50% predicted
- Minor criteria
  - Age >= 75
  - FEV1 51-60% predicted
  - DLCO 51-60% predicted
  - Pulmonary hypertension (defined as a pulmonary artery systolic pressure greater than 40 mmHg) as estimated by echocardiography or right heart catheterization
  - Poor left ventricular function (defined as an ejection fraction of 40% or less)
  - Resting or exercise partial pressure of oxygen (pO2) =< 55 mm Hg or peripheral capillary oxygen saturation (SpO2) =< 88%
  - Partial pressure of carbon dioxide (pCO2) > 45 mm Hg
  - Modified Medical Research Council (MMRC) Dyspnea Scale >= 3
Patient must not have had previous intra-thoracic radiation therapy
Women of child-bearing potential must have negative serum or urine pregnancy test
No prior invasive malignancy, unless disease-free for >= 5 years prior to pre-registration (exceptions: non-melanoma skin cancer, in-situ cancers)
PART II: INTRA-OPERATIVE CRITERIA (REGISTRATION)
Patient must have biopsy-proven NSCLC
Patient must have all suspicious mediastinal lymph nodes (> 1 cm short-axis dimension on CT scan or positive on positron emission tomography [PET] scan) assessed by one of the following methods to confirm negative involvement with NSCLC (mediastinoscopy, endo-esophageal ultrasound guided needle aspiration, CT-guided, video-assisted thoracoscopic or open lymph node biopsy)

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I	surgery	Patients undergo open or thoracoscopic sublobar resection comprising either a wedge resection or anatomical segmentectomy.
Arm II	brachytherapy	Patients undergo surgery as in arm I. Patients also undergo intraoperative brachytherapy comprising an iodine I 125 implant at the resection margin.
Arm II	surgery	Patients undergo surgery as in arm I. Patients also undergo intraoperative brachytherapy comprising an iodine I 125 implant at the resection margin.

Primary Outcome Measures

Name	Time	Method
Time to Local Recurrence	Up to 3 years	Local recurrence included the recurrence within the same lobe or hilum (N1 nodes), or progression at the staple line after treatment effects such as scarring have subsided. Time to local recurrence was censored 1) at the time of a distant recurrence, 2) at the last follow-up time when a patient died within 3 years of randomization without a local recurrence or 3) at 3 years follow-up if the patient remains alive 3 years post-randomization without a local recurrence.

Secondary Outcome Measures

Name	Time	Method
Mortality Rates at 30- and 90-day After Sublobar Resection	90 days
Overall Survival (OS)	Up to 5 years	OS was defined as the time from randomization to death due to any cause.
Number of Participants Reported Local Recurrence at 3 Years	3 years	Local recurrence was defined as the recurrence within the same lobe or hilum (N1 nodes), or at the staple line after treatment effects such as scarring have subsided.
Number of Participants Reported Regional Recurrence at 3 Years	3 years	Regional recurrence was defined as the recurrence within another lobe or pleura on the same side as the resection, or the ipsilateral mediastinal (N2) nodes.
Number of Participants Reported Distant Recurrence at 3 Years	3 years	Distant recurrence was defined as the recurrence within contralateral lobe, contralateral mediastinal (N3) nodes or distant\> metastatic disease (other organs).
Number of Participants Reported Grade 3+ Adverse Events Within 90 Days After Sublobar Resection	90 days	Adverse Events were assessed via the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.
Number of Participants Reported Grade 3+ Respiratory Adverse Events Within 90 Days After Sublobar Resection	90 days	The respiratory AE included adult respiratory distress syndrome, aspiration, bronchospasm, bronchostenosis, dyspnea, hypoxia, pleural effusion, pneumonitis, chest tube drainage or leak, prolonged intubation, pulmonary-other, and pneumonia as defined by the CTCAE version 3.0.
Global QOL as Measured Using SF36 at Baseline, Month 3, 12 and 24	24 months	Short-form health survey (SF36) consist of 36 items, where scores can be reported as 8 domains of functional health and well-being, or transformed into a physical component summary (PCS) score and a mental component summary (MCS) score. Standardized scores of SF36 PCS and MCS scores were calculated using the mean, SD, and scoring coefficients from the US general population. The standardized scores were then adjusted for age and gender using the mean and SD of the US general population according to age and gender grouping, and employing a linear transformation. Scores \<50 indicate below-average health status.
Dyspnea as Measured Using SOBQ at Baseline, Months 3, Months 12 and 24	24 months	Dyspnea was evaluated using the University of California, San Diego Shortness of Breath Questionnaire (SOBQ). It consists of 24-item on a scale of 0 to 5 with 0=not at all and 5=maximal or unable to do because of breathlessness. The total scores was calculated by summation of the 24 items scores and transformed into 0-100, with 0= poor quality of life , and 100= excellent quality of life..
FEV1% Measured at Baseline and Month 3	3 months	Pulmonary function tests included percentage predicted forced expiratory volume in 1 second (FEV1%) at baseline and month 3 were compared between arms
DLCO% Measured at Baseline and Month 3	3 months	Pulmonary function tests included percentage predicted carbon \> monoxide diffusing capacity of the lung (DLCO%) at baseline and month 3 were compared between arms.

Trial Locations

Locations (38): Mayo Clinic - Jacksonville
🇺🇸
Jacksonville, Florida, United States
Mayo Clinic Scottsdale
🇺🇸
Scottsdale, Arizona, United States
Evanston Hospital
🇺🇸
Evanston, Illinois, United States
Cancer Institute at St. John's Hospital
🇺🇸
Springfield, Illinois, United States
Regional Cancer Center at Memorial Medical Center
🇺🇸
Springfield, Illinois, United States
Simmons Cooper Cancer Institute
🇺🇸
Springfield, Illinois, United States
Cancer Institute at St. Joseph Medical Center
🇺🇸
Towson, Maryland, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
🇺🇸
Saint Louis, Missouri, United States
South Nassau Communities Hospital
🇺🇸
Oceanside, New York, United States
James P. Wilmot Cancer Center at University of Rochester Medical Center
🇺🇸
Rochester, New York, United States
SUNY Upstate Medical University Hospital
🇺🇸
Syracuse, New York, United States
Presbyterian Cancer Center at Presbyterian Hospital
🇺🇸
Charlotte, North Carolina, United States
Jameson Memorial Hospital - North Campus
🇺🇸
New Castle, Pennsylvania, United States
McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
🇺🇸
Reading, Pennsylvania, United States
Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
🇺🇸
Murray, Utah, United States
Rhode Island Hospital Comprehensive Cancer Center
🇺🇸
Providence, Rhode Island, United States
U.T. Medical Center Cancer Institute
🇺🇸
Knoxville, Tennessee, United States
University of Virginia Cancer Center
🇺🇸
Charlottesville, Virginia, United States
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
🇺🇸
Madison, Wisconsin, United States
London Regional Cancer Program at London Health Sciences Centre
🇨🇦
London, Ontario, Canada
Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
🇺🇸
Seattle, Washington, United States
Winship Cancer Institute of Emory University
🇺🇸
Atlanta, Georgia, United States
Valley Hospital - Ridgewood
🇺🇸
Ridgewood, New Jersey, United States
Boston University Cancer Research Center
🇺🇸
Boston, Massachusetts, United States
Abramson Cancer Center of the University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Mayo Clinic Cancer Center
🇺🇸
Rochester, Minnesota, United States
Charles M. Barrett Cancer Center at University Hospital
🇺🇸
Cincinnati, Ohio, United States
Knight Cancer Institute at Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
Fox Chase Cancer Center - Philadelphia
🇺🇸
Philadelphia, 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
UPMC Cancer Centers
🇺🇸
Pittsburgh, Pennsylvania, United States
Methodist Hospital
🇺🇸
Houston, Texas, United States
Floyd and Delores Jones Cancer Institute at Virginia Mason Medical Center
🇺🇸
Seattle, Washington, United States
Miriam Hospital
🇺🇸
Providence, Rhode Island, United States
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
🇺🇸
Lebanon, New Hampshire, United States
University of California Davis Cancer Center
🇺🇸
Sacramento, California, United States
University of Michigan Comprehensive Cancer Center
🇺🇸
Ann Arbor, Michigan, United States