Clinical trial NCT02984761: Veterans Affairs Lung Cancer Surgery Or Stereotactic Radiotherapy
Official title: CSP #2005 - Veterans Affairs Lung Cancer Surgery Or Stereotactic Radiotherapy Trial (VALOR)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Lung Neoplasm
Keywords: Carcinoma, Non-Small Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Radiosurgery
Radiotherapy
Radiotherapy, Image-Guided
Lung Neoplasms
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2016-12-07
Enrollment: 670
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: Patients with stage I non-small cell lung cancer have been historically treated with surgery whenever they are fit for an operation. However, an alternative treatment known as stereotactic radiotherapy now appears to offer an equally effective alternative. Doctors believe both are good treatments and are therefore conducting this study to determine if one may be possibly better than the other.

Detailed description: The standard of care for stage I non-small cell lung cancer has historically been surgical resection in patients who are medically fit to tolerate an operation. Recent data now suggests that stereotactic radiotherapy may be a suitable alternative. This includes the results from a pooled analysis of two incomplete phase III studies that reported a 15% overall survival advantage with stereotactic radiotherapy at 3 years. While these data are promising, the median follow-up period was short, the results underpowered, and the findings were in contradiction to multiple retrospective studies that demonstrate the outcomes with surgery are likely equal or superior. Therefore, the herein trial aims to evaluate these two treatments in a prospective randomized fashion with a goal to compare the overall survival beyond 5 years. It has been designed to enroll patients who have a long life-expectancy, and are fit enough to tolerate an anatomic pulmonary resection with intraoperative lymph node sampling.

This study is designed to open at Veterans Affairs medical centers with expertise in both treatments. The recruitment process includes shared decision making and multi-disciplinary evaluations with lung cancer specialists. Mandatory evaluations before randomization include tissue confirmation of NSCLC, staging with FDG-PET/CT, and biopsies of all hilar and/or mediastinal lymph nodes \>10mm that have a SUV \>2.5. Pre-randomization elective lymph node sampling is strongly encouraged, but not required. Following treatment, patients will be followed for a minimum of 5 years.

Eligibility criteria: Inclusion Criteria:

Inclusion Criteria for Screening

* Age 18 or older
* Any patient with a preliminary diagnosis of stage I Non-Small Cell Lung Cancer (NSCLC), whether pathologically proven by biopsy, or highly suspicious by radiographic imaging. \[Participants will ultimately need biopsy confirmation before enrolling\]
* Primary tumor size less than or equal to 5 cm by CT (may include CT images from PET/CT)
* Karnofsky performance status greater than or equal to 70
* Participant has willingness and ability to provided informed consent for participation

Inclusion Criteria for Randomization

* Biopsy proven non-small cell lung cancer
* Participant's case reviewed at multidisciplinary conference
* Tumor size less than or equal to 5cm (measured on the most recent CT images available, and may include PET/CT images)
* Tumor is equal to or greater than 1.0cm from the trachea, esophagus, brachial plexus, 1st bifurcation of the proximal bronchial tree, or spinal cord (measured on the most recent CT images available, and may include PET/CT images).
* Mandatory FDG-PET/CT within 60 days of the randomization date (note: FDG-PET/CT may need to be repeated prior to treatment if outside of this requirement)
* Mandatory pathological assessment of any lymph nodes \>10mm with a SUV \>2.5 seen on FDG- PET/CT
* Mandatory biopsy of any additional concerning lesions seen on FDG-PET/CT, to make better determination that the patient is not harboring metastatic disease or a secondary primary malignancy.
* Pre-operative FEV1 greater than or equal to 40% of predicted value and pre-operative DLCO greater than or equal to 40% of predicted value.
* Formally evaluated and documented by a local thoracic surgeon to be medically fit to undergo a complete anatomic pulmonary resection (wedge resection not allowed)
* Formally evaluated and documented by a local radiation oncologist to be eligible to receive protocol-defined stereotactic radiotherapy
* Participant willingness to be randomized

Exclusion Criteria:

Exclusion Criteria for Screening

* Previously evaluated by a local thoracic surgeon and determined to be medically inoperable
* Pathological confirmation of nodal or distant metastasis
* Prior history of lung cancer, not including current lesion
* Prior history of thoracic surgery or lung or esophageal cancer. \[prior cardiac surgery acceptable\]
* Prior history of radiotherapy to the thorax
* Prior history of invasive state I-III malignancy treated with surgery, radiation therapy, chemotherapy, immunotherapy, or targeted therapy in the past 2 years, excluding prostate cancer, low-risk papillary thyroid cancer (less than or equal to 1 cm), follicular lymphoma, or chronic lymphocytic leukemia.
* Prior history of IV malignancy, excluding follicular lymphoma, chronic lymphocytic leukemia, or hormone sensitive prostate cancer confined to the pelvis.
* Ever diagnosed with stage IV metastatic cancer of any type
* History of scleroderma
* Positive Pregnancy test (for women \<61 years of age or without prior hysterectomy)

Exclusion Criteria for Randomization

* Pathological confirmation of nodal or metastatic disease

Primary outcomes:
measure: Overall Survival
timeFrame: From date of randomization through study completion, up to 10 years
Secondary outcomes:
measure: Patient reported health-related quality of life
timeFrame: 5 years
measure: Respiratory Function
timeFrame: 5 years
measure: Health State Utilities
timeFrame: 5 years
measure: Lung cancer mortality
timeFrame: From date of randomization until date of death from any cause, assessed up to 10 years.
measure: Tumor patterns of failure
timeFrame: 5 years
measure: Respiratory Function
timeFrame: 5 years
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: VA Long Beach Healthcare System, Long Beach, CA
state: California
city: West Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System, West Los Angeles, CA
state: California
city: Bay Pines
country: United States
facility: Bay Pines VA Healthcare System, Pay Pines, FL
state: Florida
city: Miami
country: United States
facility: Miami VA Healthcare System, Miami, FL
state: Florida
city: Hines
country: United States
facility: Edward Hines Jr. VA Hospital, Hines, IL
state: Illinois
city: Indianapolis
country: United States
facility: Richard L. Roudebush VA Medical Center, Indianapolis, IN
state: Indiana
city: Baltimore
country: United States
facility: Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD
state: Maryland
city: Boston
country: United States
facility: VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
state: Massachusetts
city: Ann Arbor
country: United States
facility: VA Ann Arbor Healthcare System, Ann Arbor, MI
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis VA Health Care System, Minneapolis, MN
state: Minnesota
city: Durham
country: United States
facility: Durham VA Medical Center, Durham, NC
state: North Carolina
city: Cleveland
country: United States
facility: Louis Stokes VA Medical Center, Cleveland, OH
state: Ohio
city: Philadelphia
country: United States
facility: Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
state: Pennsylvania
city: Pittsburgh
country: United States
facility: VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
state: Pennsylvania
city: Houston
country: United States
facility: Michael E. DeBakey VA Medical Center, Houston, TX
state: Texas
city: Richmond
country: United States
facility: Hunter Holmes McGuire VA Medical Center, Richmond, VA
state: Virginia
city: Milwaukee
country: United States
facility: Clement J. Zablocki VA Medical Center, Milwaukee, WI
state: Wisconsin
Study officials:
affiliation: VA Greater Los Angeles Healthcare System, West Los Angeles, CA
name: Drew Moghanaki, MD MPH
role: STUDY_CHAIR
affiliation: Durham VA Medical Center, Durham, NC
name: David H Harpole, MD
role: STUDY_CHAIR
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.