Clinical trial NCT00003831: Lymph Node Removal in Treating Patients With Stage I or Stage II Non-small Cell Lung Cancer
Official title: Randomized Trial of Mediastinal Lymph Node Sampling Versus Complete Lymphadenectomy During Pulmonary Resection in the Patient With N0 and N1 (Less Than Hilar) Non-Small Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Cancer
Keywords: stage I non-small cell lung cancer
stage II non-small cell lung cancer
squamous cell lung cancer
large cell lung cancer
adenocarcinoma of the lung
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 1023
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: Surgical removal of all lymph nodes in the chest may kill cancer cells that have spread from tumors in the lung. It is not yet known whether complete removal of all lymph nodes in the chest is more effective than removal of selected lymph nodes in treating patients who have stage I or stage II non-small cell lung cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of complete removal of all lymph nodes in the chest with that of selected removal of lymph nodes during lung cancer surgery in treating patients who have stage I or stage II non-small cell lung cancer.

Detailed description: OBJECTIVES:

* Compare whether a complete mediastinal lymph node dissection versus mediastinal lymph node sampling improves overall survival of patients with N0 or non-hilar N1 non-small cell lung cancer undergoing resection.
* Compare these two methods with reference to identification of occult mediastinal lymph node involvement.
* Compare the effect of these two methods on operative time and duration of postoperative complications, including chest tube drainage and length of hospitalization for these patients.
* Compare the effect of these two methods on local recurrence free survival and local regional recurrence free survival of these patients.

Eligibility criteria: Inclusion Criteria:

A patient will be eligible for inclusion in this study only if ALL of the following criteria apply:

Pre-operative:

1. Patient must be ≥18 years of age.
2. Patient must have an ECOG/Zubrod performance status of ≤ 3.
3. Patient must have tissue diagnosis of a clinically resectable T1 or T2, N0 or non-hilar N1, M0 NSCLC (squamous cell carcinoma, large cell carcinoma or adenocarcinoma including bronchoalveolar carcinoma) established prior to randomization. NOTE: A patient without a pre-operative tissue diagnosis, but with clinically suspected NSCLC that fits the above criteria is eligible provided the tissue diagnosis is confirmed intraoperatively.
4. Patient must have pre-operative imaging procedure, CT scan of the chest and upper abdomen to include liver and adrenal glands to determine eligibility, within 60 days of the date of the pulmonary resection.
5. Patient that has not had a mediastinoscopy should have no mediastinal adenopathy on the CT of the chest defined as no lymph node \> 1 cm in the shortest axis.
6. Patient is a candidate for a complete resection of the carcinoma via pneumonectomy,lobectomy, bilobectomy, or anatomic segmentectomy with or without sleeve resection,as noted in the surgical plan.
7. Patient, or patient's legally acceptable representative, must provide a signed and dated Z0030-specific written informed consent prior to registration and any study-related procedures.
8. If patient is a survivor of a prior cancer, the following criteria are met:

   1. Patient has undergone potentially curative therapy for all prior malignancies,
   2. No evidence of any prior malignancies for at least 5 years with no evidence of recurrence (except for effectively treated basal cell or squamous carcinoma of the skin, carcinoma in-situ of the cervix that has been effectively treated by surgery alone, or lobular carcinoma in-situ of the ipsilateral or contralateral breast treated by surgery alone),
   3. Patient is deemed by their treating physician to be at low risk for recurrence from prior malignancies.

Intra-operative:

1. Patient with right-sided lesions must have at least nodal stations #2R, 4R, 7 and 10 R examined. If the nodes are found, they must be sampled and proven negative by frozen section.
2. Patient with left-sided lesions must have at least nodal stations #5, 6, 7 and 10L examined. If the nodes are found, they must be sampled and proven negative by frozen section.
3. Any other suspicious mediastinal or hilar nodes must be sampled and proven negative by frozen section. Levels 2, 4 and 7 need not be re-sampled if they were sampled at a mediastinoscopy done within 60 days of thehoracotomy.

Exclusion Criteria:

A patient will NOT be eligible for inclusion in this study if ANY of the following criteria apply:

1. Patient has N2 disease determined at pre-operative mediastinoscopy or on sampling.
2. Patient has T3 or T4 tumor.
3. Patient is having only a wedge resection performed for treatment.
4. Patient has received prior chemotherapy or radiotherapy for this cancer.

Primary outcomes:
measure: Overall survival
timeFrame: Up to 5 years
Secondary outcomes:
measure: Disease-free survival
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Mobile Infirmary Medical Center
state: Alabama
city: Los Angeles
country: United States
facility: Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center
state: California
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center at University of California Irvine Cancer Center
state: California
city: Pasadena
country: United States
facility: Huntington Cancer Center at Huntington Hospital
state: California
city: San Francisco
country: United States
facility: UCSF Comprehensive Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Gainesville
country: United States
facility: Veterans Affairs Medical Center - Gainesville
state: Florida
city: Gainesville
country: United States
facility: Shands Cancer Center at the University of Florida
state: Florida
city: Melbourne
country: United States
facility: Holmes Regional Medical Center
state: Florida
city: Miami
country: United States
facility: Jackson Memorial Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Macon
country: United States
facility: Medical Center of Central Georgia
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Elk Grove Village
country: United States
facility: Alexian Brothers Medical Center
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Naperville
country: United States
facility: Edward Hospital Cancer Center
state: Illinois
city: Springfield
country: United States
facility: St. John's Hospital
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Lexington
country: United States
facility: Central Baptist Hospital
state: Kentucky
city: Louisville
country: United States
facility: Jewish Hospital
state: Kentucky
city: Lafayette
country: United States
facility: Medical Center of Southwest Louisiana
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Rhode Island Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital - Royal Oak
state: Michigan
city: Duluth
country: United States
facility: St. Luke's Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Veterans Affairs Medical Center - Minneapolis
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center at University of Missouri - Columbia
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Omaha
country: United States
facility: Veterans Affairs Medical Center - Omaha
state: Nebraska
city: Omaha
country: United States
facility: Creighton University School of Medicine
state: Nebraska
city: Englewood
country: United States
facility: Englewood Hospital Oncology Program
state: New Jersey
city: Ridgewood
country: United States
facility: Valley Hospital
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Cooperstown
country: United States
facility: Louis Busch Hager Cancer Center at Mary Imogene Bassett Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: New York Weill Cornell Cancer Center at Cornell University
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: Long Island Cancer Center at Stony Brook University Hospital
state: New York
city: Minot
country: United States
facility: Trinity Hospital
state: North Dakota
city: Cincinnati
country: United States
facility: Veterans Affairs Medical Center - Cincinnati
state: Ohio
city: Cincinnati
country: United States
facility: Tri-Health Good Samaritan Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
city: Portland
country: United States
facility: Earle A. Chiles Research Institute at Providence Portland Medical Center
state: Oregon
city: Greensburg
country: United States
facility: Westmoreland Regional Hospital
state: Pennsylvania
city: New Castle
country: United States
facility: Jameson Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Abramson Cancer Center at University of Pennsylvania Medical Center
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
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburg Medical Center - Shadyside Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Presbyterian-University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC St. Margaret
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Pennsylvania Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: St. Clair Memorial Hospital
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Cancer Center at Lankenau Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: Saint Thomas Hospital
state: Tennessee
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Charlottesville
country: United States
facility: Cancer Center at the University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Massey Cancer Center
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Seattle
country: United States
facility: Veterans Affairs Medical Center - Seattle
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Hospitals
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital
state: Victoria
city: London
country: Canada
facility: Cancer Care Ontario-London Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
Study officials:
affiliation: Mayo Clinic
name: Mark S. Allen, MD
role: STUDY_CHAIR
References:
citation: Potti A, Mukherjee S, Petersen R, Dressman HK, Bild A, Koontz J, Kratzke R, Watson MA, Kelley M, Ginsburg GS, West M, Harpole DH Jr, Nevins JR. A genomic strategy to refine prognosis in early-stage non-small-cell lung cancer. N Engl J Med. 2006 Aug 10;355(6):570-80. doi: 10.1056/NEJMoa060467.
citation: Fibla JJ, Cassivi SD, Brunelli A, Decker PA, Allen MS, Darling GE, Landreneau RJ, Putnam JB. Re-evaluation of the prognostic value of visceral pleura invasion in Stage IB non-small cell lung cancer using the prospective multicenter ACOSOG Z0030 trial data set. Lung Cancer. 2012 Dec;78(3):259-62. doi: 10.1016/j.lungcan.2012.09.010. Epub 2012 Oct 3.
citation: Darling GE, Allen MS, Decker PA, Ballman K, Malthaner RA, Inculet RI, Jones DR, McKenna RJ, Landreneau RJ, Putnam JB Jr. Number of lymph nodes harvested from a mediastinal lymphadenectomy: results of the randomized, prospective American College of Surgeons Oncology Group Z0030 trial. Chest. 2011 May;139(5):1124-1129. doi: 10.1378/chest.10-0859. Epub 2010 Sep 9.
citation: Darling GE, Allen MS, Decker PA, Ballman K, Malthaner RA, Inculet RI, Jones DR, McKenna RJ, Landreneau RJ, Rusch VW, Putnam JB Jr. Randomized trial of mediastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 (less than hilar) non-small cell carcinoma: results of the American College of Surgery Oncology Group Z0030 Trial. J Thorac Cardiovasc Surg. 2011 Mar;141(3):662-70. doi: 10.1016/j.jtcvs.2010.11.008.
citation: Allen MS, Darling GE, Pechet TT, Mitchell JD, Herndon JE 2nd, Landreneau RJ, Inculet RI, Jones DR, Meyers BF, Harpole DH, Putnam JB Jr, Rusch VW; ACOSOG Z0030 Study Group. Morbidity and mortality of major pulmonary resections in patients with early-stage lung cancer: initial results of the randomized, prospective ACOSOG Z0030 trial. Ann Thorac Surg. 2006 Mar;81(3):1013-9; discussion 1019-20. doi: 10.1016/j.athoracsur.2005.06.066.