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

Study Overview
=================
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.

Official Title
-----------------
A Randomized Phase III Study of Sublobar Resection Versus Sublobar Resection Plus Brachytherapy in High Risk Patients With Non-Small Cell Lung Cancer (NSCLC), 3cm or Smaller

Conditions
-----------------
Lung Cancer

Intervention / Treatment
-----------------
* Procedure: surgery
* Radiation: brachytherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I<br>Patients undergo open or thoracoscopic sublobar resection comprising either a wedge resection or anatomical segmentectomy. | Procedure: surgery<br> <br> |
| Experimental: Arm II<br>Patients undergo surgery as in arm I. Patients also undergo intraoperative brachytherapy comprising an iodine I 125 implant at the resection margin. | Procedure: surgery<br> <br> Radiation: brachytherapy<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Local Recurrence | 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. | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS was defined as the time from randomization to death due to any cause. | Up to 5 years | 
| Number of Participants Reported Local Recurrence at 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. | 3 years | 
| Number of Participants Reported Regional Recurrence at 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. | 3 years | 
| Number of Participants Reported Distant Recurrence at 3 Years | Distant recurrence was defined as the recurrence within contralateral lobe, contralateral mediastinal (N3) nodes or distant> metastatic disease (other organs). | 3 years | 
| Mortality Rates at 30- and 90-day After Sublobar Resection |  | 90 days | 
| Number of Participants Reported Grade 3+ Adverse Events Within 90 Days After Sublobar Resection | Adverse Events were assessed via the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. | 90 days | 
| Number of Participants Reported Grade 3+ Respiratory Adverse Events Within 90 Days After Sublobar Resection | 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. | 90 days | 
| Global QOL as Measured Using SF36 at Baseline, Month 3, 12 and 24 | 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. | 24 months | 
| Dyspnea as Measured Using SOBQ at Baseline, Months 3, Months 12 and 24 | 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.. | 24 months | 
| FEV1% Measured at Baseline and Month 3 | Pulmonary function tests included percentage predicted forced expiratory volume in 1 second (FEV1%) at baseline and month 3 were compared between arms | 3 months | 
| DLCO% Measured at Baseline and Month 3 | Pulmonary function tests included percentage predicted carbon > monoxide diffusing capacity of the lung (DLCO%) at baseline and month 3 were compared between arms. | 3 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage I non-small cell lung cancer