Clinical trial NCT02468024: JoLT-Ca Sublobar Resection (SR) Versus Stereotactic Ablative Radiotherapy (SAbR) for Lung Cancer
Official title: JoLT-Ca A Randomized Phase III Study of Sublobar Resection (SR) Versus Stereotactic Ablative Radiotherapy (SAbR) in High Risk Patients With Stage I Non-Small Cell Lung Cancer (NSCLC), The STABLE-MATES Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2015-06-10
Enrollment: 272
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Surgery versus SAbR
Primary purpose: TREATMENT

Brief summary: To Determine if SAbR improves survival over SR in High Risk Operable Stage I NSCLC

Detailed description: Stereotactic Ablative Radiotherapy has been shown in single institution phase II and matched cohort studies to be effective at controlling primary early lung cancer. Recent pooled analysis of both the STARS and ROSEL randomized trials comparing SABR versus lobectomy have shown a significantly improved 3-year survival with SABR, giving further impetus for successful completion of a randomized trial .

Pre-randomized trial- Patients will be screened and pre-randomized to either SR or SAbR. Informed consent will be obtained after patients are made aware of the randomized assignment. Despite pre-randomization prior to consent, patients maintain their right to accept or decline any/all study activities. Only consenting patients will be allowed to participate in study activities, including observation after either randomized treatments or observation after standard of care treatment, while those declining consent will be managed by their physician(s) off study.Patients will be accrued and followed for a minimum of 2-years after treatment.

Eligibility criteria: 1.0 Inclusion Criteria

1.1 Age \> 18 years.

1.2 ECOG/Zubrod performance status (PS) 0, 1, or 2 (reference Appendix C).

1.3 Radiographic findings consistent with non-small cell lung cancer, including lesions with ground glass opacities with a solid component of 50% or greater.

1.4 The primary tumor in the lung must be biopsy confirmed non-small cell lung cancer within 180 days prior to randomization.

1.5 Tumor ≤ 4 cm maximum diameter, including clinical stage IA and selected IB by PET or PET integrated with a simultaneous CT scan (PET-CT) of the chest and upper abdomen performed within 180 days prior to randomization (reference Appendix A \& B). Repeat imaging within 90 days prior to randomization is recommended for re-staging but is not required based on institutional norms.

1.6 All clinically suspicious mediastinal N1, N2, or N3 lymph nodes (\> 1 cm short-axis dimension on CT scan and/or positive on PET scan) confirmed negative for involvement with NSCLC by one of the following methods: mediastinoscopy, anterior mediastinotomy, EUS/EBUS guided needle aspiration, CT-guided, video-assisted thoracoscopic or open lymph node biopsy within 180 days of randomization.

1.7 Tumor verified by a thoracic surgeon to be in a location that will permit sublobar resection.

1.8 Tumor located peripherally within the lung. NOTE: Peripheral is defined as not touching any surface within 2 cm of the proximal bronchial tree in all directions. See bronchial tree diagram below. Patients with non-peripheral (central) tumors are NOT eligible.

1.9 No evidence of distant metastases.

1.10 Availability of pulmonary function tests (PFTs - spirometry, DLCO, +/- arterial blood gases) within 180 days prior to registration. Patients with tracheotomy, etc, who are physically unable to perform PFTs (and therefore cannot be tested for the Major criteria in 3.1.11 below) are potentially still eligible if a study credentialed thoracic surgeon documents that the patient's health characteristics would otherwise have been acceptable for eligibility as a high risk but nonetheless operable patient (in particular be eligible for sublobar resection).

1.11 To define eligibility of patients being at high risk for surgery, certain criteria must be met.

Any one (1) of the following major criteria will define the high risk status for eligibility:

Major Criteria

* FEV1 ≤ 50% predicted (pre-bronchodilator value)
* DLCO ≤ 50% predicted (pre-bronchodilator value)
* Study credentialed thoracic surgeon believes the patient is potentially operable but that a lobectomy or pneumonectomy would be poorly tolerated by the patient for tangible or intangible reasons. The belief must be declared and documented in the medical record prior to randomization.

If any of the major criteria are met, the patient is eligible based on high risk for surgery and minor criteria do not need to be considered. However, if no major criteria is met, at least two (2) minor criteria being met will also define eligibility for meeting the high risk status.

Any two (2) of the following minor criteria will define the high risk status for eligibility:

* Minor Criteria
* Age ≥75
* FEV1 51-60% predicted (pre-bronchodilator value)
* DLCO 51-60% predicted (pre-bronchodilator value)
* Pulmonary hypertension (defined as a pulmonary artery systolic pressure greater than 40mm Hg) as estimated by echocardiography or right heart catheterization
* Poor left ventricular function (defined as an ejection fraction of 40% or less)
* Resting or Exercise Arterial pO2 ≤ 55 mm Hg or SpO2 ≤ 88%
* pCO2 \> 45 mm Hg
* Modified Medical Research Council (MMRC) Dyspnea Scale ≥ 3.

1.12 No prior intra-thoracic radiation therapy for previously identified intra-thoracic primary tumor (e.g. previous lung cancer) on the ipsilateral side. NOTE: Previous radiotherapy as part of treatment for head and neck, breast, or other non-thoracic cancer is permitted to the ipsilateral side so long as possible radiation fields would not overlap. NOTE: Radiotherapy to the contralateral lung is allowed so long as it was completed more than 3 years prior to randomization and there is no overlap of radiation fields.

1.13 Previous chemotherapy, radiotherapy, or surgical resection specifically for the lung cancer being treated on this protocol is NOT permitted.

1.14 No prior lung resection on the ipsilateral side.

1.15 Non-pregnant and non-lactating. Women of child-bearing potential must have a negative urine or serum pregnancy test prior to registration. Peri-menopausal women must be amenorrheic \> 12 months prior to registration to be considered not of childbearing potential.

1.16 No prior invasive malignancy, unless disease-free for ≥ 3 years prior to registration (exceptions: non-melanoma skin cancer, in-situ cancers).

1.17 Ability to understand and sign a written informed consent.

2.0 Exclusion Criteria

2.1 Age \<18

2.2 ECOG/Zubrod performance status (PS) greater than 3.

2.3 Radiographic findings with ground glass opacities and less than 50% solid component will be excluded.

2.4 The primary tumor in the lung, biopsy confirmed non-small cell lung cancer greater than 180 days prior to randomization.

2.5 Tumor \> 5 cm maximum diameter, including clinical stage IA and selected IB by PET or PET integrated with a simultaneous CT scan (PET-CT) of the chest and upper abdomen and/or performed greater than 180 days prior to randomization.

2.6 Lymph node biopsy greater than 180 days prior to randomization.

2.7 Thoracic surgeon confirms unable to remove tumor with sublobar resection.

2.8 Tumor located non-peripheral (central) region of lung (see bronchial tree diagram in 3.1.8).

2.9 Evidence of distant metastases.

2.10 Pulmonary function test (PFT - spirometry, DLCO, +/- arterial blood gases) greater than 180 days prior to registration. Patients physically unable to perform PFT's, such as patients with tracheotomy, that do not have written documentation from study credentialed thoracic surgeon stating eligibility.

2.11 Patients that do not meet either Major criteria or Minor criteria.

2.12 Prior intra-thoracic radiation therapy on ipsilateral side. Radiotherapy to the contralateral lung completed less than 3 years prior to randomization, with radiation field overlap.

2.13 Prior chemotherapy, radiotherapy, or surgical resection specifically for the lung cancer being treated on this protocol.

2.14 Prior lung resection on the ipsilateral side.

2.15 Pregnant and lactating women.

2.16 Prior invasive malignancy and less than 3 years disease free prior to registration (unless non-melanoma skin cancer, in-situ cancers).

2.17 Unable to understand and/ or sign a written informed consent.

Primary outcomes:
measure: overall survival
timeFrame: 3 years
Secondary outcomes:
measure: progression free survival
timeFrame: 5 years
measure: toxicity as assessed toxicity using the Common Toxicity Criteria
timeFrame: 3 years
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UCSD
state: California
city: Aurora
country: United States
facility: University of Colorado/Memorial
state: Colorado
city: Colorado Springs
country: United States
facility: Penrose Cancer Center
state: Colorado
city: Boca Raton
country: United States
facility: Boca Raton Regional Hospital
state: Florida
city: Savannah
country: United States
facility: Curtis and Elizabeth Anderson Cancer
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Health Care
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville Physicians
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Annapolis
country: United States
facility: Luminis Health Research Institute
state: Maryland
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Royal Oak
country: United States
facility: Beaumont
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Neptune
country: United States
facility: Meridian Health System
state: New Jersey
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY - Upsate Medical Centre
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Case Western (University Hospitals Case Medical Center)
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Portland
country: United States
facility: Providence Health & Services/Oregon Clinic
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Health System
state: Pennsylvania
city: Pittsburg
country: United States
facility: Allegheny
state: Pennsylvania
city: State College
country: United States
facility: Mount Nittany
state: Pennsylvania
city: Providence
country: United States
facility: Lifespan Oncology Clinical Research
state: Rhode Island
city: Memphis
country: United States
facility: University of Tennessee Health Science Center
state: Tennessee
city: Austin
country: United States
facility: Cardiothoracic and Vascular Surgeons
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: Intermountain Medical Center
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Falls Church
country: United States
facility: Inova Fairfax Medical Campus
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Clement Zablocki VA Medical Center
state: Wisconsin
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital Melbourne
state: Melbourne
city: Fitzroy
country: Australia
facility: St. Vincent's/Peter Mac
state: Victoria
city: Geelong
country: Australia
facility: Barwon Health - Uni Hospital Geelong
state: Victoria
city: London
country: Canada
facility: Lawson Health Science Center
state: Ontario, Canada
city: Ottawa
country: Canada
facility: Ottawa Hospital Cancer Center
state: Ontario
city: Toronto
country: Canada
facility: UHN-Toronto
state: Ontario
city: Montréal
country: Canada
facility: CHUM
state: Quebec
city: Mississauga
country: Canada
facility: Trillium Health Partners
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
city: Middlesbrough
country: United Kingdom
facility: The James Cook University Hospital
Study officials:
affiliation: UTSW Medical Center
name: Robert Timmerman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Elbanna M, Shiue K, Edwards D, Cerra-Franco A, Agrawal N, Hinton J, Mereniuk T, Huang C, Ryan JL, Smith J, Aaron VD, Burney H, Zang Y, Holmes J, Langer M, Zellars R, Lautenschlaeger T. Impact of Lung Parenchymal-Only Failure on Overall Survival in Early-Stage Lung Cancer Patients Treated With Stereotactic Ablative Radiotherapy. Clin Lung Cancer. 2021 May;22(3):e342-e359. doi: 10.1016/j.cllc.2020.05.024. Epub 2020 Jun 2.