Clinical trial NCT00107172: Surgery With or Without Internal Radiation Therapy in Treating Patients With Stage I Non-Small Cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Cancer
Keywords: stage I non-small cell lung cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-04-06
Enrollment: 224
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: 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.

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)

Primary outcomes:
measure: Time to Local Recurrence
timeFrame: Up to 3 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to 5 years
measure: Number of Participants Reported Local Recurrence at 3 Years
timeFrame: 3 years
measure: Number of Participants Reported Regional Recurrence at 3 Years
timeFrame: 3 years
measure: Number of Participants Reported Distant Recurrence at 3 Years
timeFrame: 3 years
measure: Mortality Rates at 30- and 90-day After Sublobar Resection
timeFrame: 90 days
measure: Number of Participants Reported Grade 3+ Adverse Events Within 90 Days After Sublobar Resection
timeFrame: 90 days
measure: Number of Participants Reported Grade 3+ Respiratory Adverse Events Within 90 Days After Sublobar Resection
timeFrame: 90 days
measure: Global QOL as Measured Using SF36 at Baseline, Month 3, 12 and 24
timeFrame: 24 months
measure: Dyspnea as Measured Using SOBQ at Baseline, Months 3, Months 12 and 24
timeFrame: 24 months
measure: FEV1% Measured at Baseline and Month 3
timeFrame: 3 months
measure: DLCO% Measured at Baseline and Month 3
timeFrame: 3 months
Other outcomes:
Locations:
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: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Evanston
country: United States
facility: Evanston Hospital
state: Illinois
city: Springfield
country: United States
facility: Cancer Institute at St. John's Hospital
state: Illinois
city: Springfield
country: United States
facility: Regional Cancer Center at Memorial Medical Center
state: Illinois
city: Springfield
country: United States
facility: Simmons Cooper Cancer Institute
state: Illinois
city: Towson
country: United States
facility: Cancer Institute at St. Joseph Medical Center
state: Maryland
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: 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: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Ridgewood
country: United States
facility: Valley Hospital - Ridgewood
state: New Jersey
city: Oceanside
country: United States
facility: South Nassau Communities Hospital
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital
state: New York
city: Charlotte
country: United States
facility: Presbyterian Cancer Center at Presbyterian Hospital
state: North Carolina
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Portland
country: United States
facility: Knight Cancer Institute at Oregon Health and Science University
state: Oregon
city: New Castle
country: United States
facility: Jameson Memorial Hospital - North Campus
state: Pennsylvania
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center - Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Cancer Center at Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Centers
state: Pennsylvania
city: Reading
country: United States
facility: McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital Comprehensive Cancer Center
state: Rhode Island
city: Providence
country: United States
facility: Miriam Hospital
state: Rhode Island
city: Knoxville
country: United States
facility: U.T. Medical Center Cancer Institute
state: Tennessee
city: Houston
country: United States
facility: Methodist Hospital
state: Texas
city: Murray
country: United States
facility: Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Seattle
country: United States
facility: Floyd and Delores Jones Cancer Institute at Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
state: Wisconsin
city: London
country: Canada
facility: London Regional Cancer Program at London Health Sciences Centre
state: Ontario
Study officials:
affiliation: Boston Medical Center
name: Hiran C. Fernando, MD
role: STUDY_CHAIR
References:
citation: Smith RP, Schuchert M, Komanduri K, Burton S, Heron DE, Luketich JD, d'Amato T, Landreneau R. Dosimetric evaluation of radiation exposure during I-125 vicryl mesh implants: implications for ACOSOG z4032. Ann Surg Oncol. 2007 Dec;14(12):3610-3. doi: 10.1245/s10434-007-9624-0. Epub 2007 Oct 2.
citation: Fernando HC, Landreneau RJ, Mandrekar SJ, Hillman SL, Nichols FC, Meyers B, DiPetrillo TA, Heron DE, Jones DR, Daly BD, Starnes SL, Tan A, Putnam JB. Thirty- and ninety-day outcomes after sublobar resection with and without brachytherapy for non-small cell lung cancer: results from a multicenter phase III study. J Thorac Cardiovasc Surg. 2011 Nov;142(5):1143-51. doi: 10.1016/j.jtcvs.2011.07.051. Epub 2011 Aug 26.
citation: Fernando HC, Landreneau RJ, Mandrekar SJ, Hillman SL, Nichols FC, Meyers B, DiPetrillo TA, Heron D, Jones DR, Daly BD, Starnes SL, Hatter JE, Putnam JB. The impact of adjuvant brachytherapy with sublobar resection on pulmonary function and dyspnea in high-risk patients with operable disease: preliminary results from the American College of Surgeons Oncology Group Z4032 trial. J Thorac Cardiovasc Surg. 2011 Sep;142(3):554-62. doi: 10.1016/j.jtcvs.2010.10.061. Epub 2011 Jul 2.
citation: Fernando HC, Landreneau RJ, Mandrekar SJ, Nichols FC, Hillman SL, Heron DE, Meyers BF, DiPetrillo TA, Jones DR, Starnes SL, Tan AD, Daly BD, Putnam JB Jr. Impact of brachytherapy on local recurrence rates after sublobar resection: results from ACOSOG Z4032 (Alliance), a phase III randomized trial for high-risk operable non-small-cell lung cancer. J Clin Oncol. 2014 Aug 10;32(23):2456-62. doi: 10.1200/JCO.2013.53.4115. Epub 2014 Jun 30.
citation: Fernando HC, Landreneau RJ, Mandrekar SJ, Nichols FC, DiPetrillo TA, Meyers BF, Heron DE, Hillman SL, Jones DR, Starnes SL, Tan AD, Daly BD, Putnam JB; Alliance for Clinical Trials in Oncology. Analysis of longitudinal quality-of-life data in high-risk operable patients with lung cancer: results from the ACOSOG Z4032 (Alliance) multicenter randomized trial. J Thorac Cardiovasc Surg. 2015 Mar;149(3):718-25; discussion 725-6. doi: 10.1016/j.jtcvs.2014.11.003. Epub 2014 Nov 13.