Veterans Affairs Lung Cancer Surgery Or Stereotactic Radiotherapy

Lung Neoplasm Clinical Trial

— VALOR  

Official title:

CSP #2005 - Veterans Affairs Lung Cancer Surgery Or Stereotactic Radiotherapy Trial (VALOR)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02984761
• Other study ID #: 2005
• Status: Recruiting
• Phase: N/A
• Start date: April 13, 2017
• Est. completion date: September 30, 2027

Study information

• Verified date: October 2023
• Source: VA Office of Research and Development
• Contact: Cheryl C Odle, MBA
• Phone: (708) 202-8387
• Email: cheryl.odle[@]va.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 670
• Est. completion date: September 30, 2027
• Est. primary completion date: September 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Neoplasm
• Lung Neoplasms
• Neoplasms

Intervention

Radiation:
• Stereotactic Radiotherapy
Stereotactic radiotherapy uses high doses of ionizing energy to treat cancer cells with image guidance. The treatment is delivered in an outpatient setting, and for purposes of this trial is delivered in 3-5 fractions.

Procedure:
• Anatomic Pulmonary Resection
An anatomic pulmonary resection is an oncologic procedure that dissects out an anatomically defined segment of the lung to remove all of the lung tissue around a lung tumor. It requires an operation with general anesthesia, with a short hospital stay. The procedure entails removal of lymph nodes inside the chest that might not be easily accessible without an operation.

Locations

Country	Name	City	State
United States	VA Ann Arbor Healthcare System, Ann Arbor, MI	Ann Arbor	Michigan
United States	Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD	Baltimore	Maryland
United States	Bay Pines VA Healthcare System, Pay Pines, FL	Bay Pines	Florida
United States	VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA	Boston	Massachusetts
United States	Louis Stokes VA Medical Center, Cleveland, OH	Cleveland	Ohio
United States	Durham VA Medical Center, Durham, NC	Durham	North Carolina
United States	Edward Hines Jr. VA Hospital, Hines, IL	Hines	Illinois
United States	Michael E. DeBakey VA Medical Center, Houston, TX	Houston	Texas
United States	Richard L. Roudebush VA Medical Center, Indianapolis, IN	Indianapolis	Indiana
United States	VA Long Beach Healthcare System, Long Beach, CA	Long Beach	California
United States	Miami VA Healthcare System, Miami, FL	Miami	Florida
United States	Clement J. Zablocki VA Medical Center, Milwaukee, WI	Milwaukee	Wisconsin
United States	Minneapolis VA Health Care System, Minneapolis, MN	Minneapolis	Minnesota
United States	Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA	Philadelphia	Pennsylvania
United States	VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA	Pittsburgh	Pennsylvania
United States	Hunter Holmes McGuire VA Medical Center, Richmond, VA	Richmond	Virginia
United States	VA Greater Los Angeles Healthcare System, West Los Angeles, CA	West Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Survival estimates will include death from any cause.	From date of randomization through study completion, up to 10 years
Secondary	Patient reported health-related quality of life	The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and Lung Cancer (LC 13) survey instruments will assess patients' general state of physical, social/family, emotional and functional well-being.	5 years
Secondary	Respiratory Function	The St George's Respiratory Questionnaire will evaluate respiratory symptoms, activity limitations from breathlessness, and impact of respiratory function on social and psychological functioning.	5 years
Secondary	Health State Utilities	The EQ-5D-5L (EuroQOL-5D) survey will measure quality adjusted life years.	5 years
Secondary	Lung cancer mortality	Cause of death will be determined by an independent adjudication committee.	From date of randomization until date of death from any cause, assessed up to 10 years.
Secondary	Tumor patterns of failure	Post-treatment surveillance imaging will evaluate patients every 6 months for local, regional, and/or distant disease control.	5 years
Secondary	Respiratory Function	The Forced Expiratory Volume at 1 second (FEV1) will evaluate an objective measure of breathing function.	5 years