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

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00107172
• Other study ID #: ACOSOG-Z4032
• Secondary ID: ACOSOG-Z4032CDR0
• Status: Completed
• Phase: Phase 3
• Start date: July 2005
• Est. completion date: February 15, 2019

Study information

• Verified date: October 2019
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 224
• Est. completion date: February 15, 2019
• Est. primary completion date: April 18, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

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

Intervention

Procedure:
• surgery

Radiation:
• brachytherapy

Locations

Country	Name	City	State
Canada	London Regional Cancer Program at London Health Sciences Centre	London	Ontario
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Boston University Cancer Research Center	Boston	Massachusetts
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Evanston Hospital	Evanston	Illinois
United States	Methodist Hospital	Houston	Texas
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	U.T. Medical Center Cancer Institute	Knoxville	Tennessee
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah
United States	Jameson Memorial Hospital - North Campus	New Castle	Pennsylvania
United States	South Nassau Communities Hospital	Oceanside	New York
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania
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	Knight Cancer Institute at Oregon Health and Science University	Portland	Oregon
United States	Miriam Hospital	Providence	Rhode Island
United States	Rhode Island Hospital Comprehensive Cancer Center	Providence	Rhode Island
United States	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania
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	University of California Davis Cancer Center	Sacramento	California
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	Floyd and Delores Jones Cancer Institute at Virginia Mason Medical Center	Seattle	Washington
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
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	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	Cancer Institute at St. Joseph Medical Center	Towson	Maryland

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 (5)

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 — View 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 cel — View 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 op — View 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 Z403 — View 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. Epub 2007 Oct 2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival (OS)	OS was defined as the time from randomization to death due to any cause.	Up to 5 years
Secondary	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
Secondary	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
Secondary	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
Secondary	Mortality Rates at 30- and 90-day After Sublobar Resection		90 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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