VALOR: Veterans Affairs Lung Cancer Surgery Or Stereotactic Radiotherapy

Sponsor

VA Office of Research and Development (U.S. Fed)

Overall Status

Recruiting

CT.gov ID

NCT02984761

Collaborator

(none)

670

Enrollment

Locations

Arms

125.6

Anticipated Duration (Months)

41.9

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lung Neoplasm	Radiation: Stereotactic Radiotherapy Procedure: Anatomic Pulmonary Resection	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

670 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 13, 2017

Anticipated Primary Completion Date :

Sep 30, 2026

Anticipated Study Completion Date :

Sep 30, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Stereotactic radiotherapy Stereotactic radiotherapy is an FDA approved treatment for lung cancer. However, for purposes of this study, it is being delivered to an operable population that is typically treated with surgical resection. Participants randomized to stereotactic radiotherapy will be treated according to the location of the tumor. Peripheral tumors will receive either 18 Gy x 3, 14 Gy x 4, or 11.5 Gy x 5 fractions, while central tumors will be treated with 10 Gy x 5. There will not be any elective coverage of local microscopic spread or regional lymph nodes.	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. Other Names: Stereotactic Body Radiation Therapy (SBRT) or Stereotactic Ablative Radiotherapy (SAbR)
Active Comparator: Surgery Participants randomized to surgery will undergo a standard lobectomy or limited anatomic pulmonary resection (segmentectomy) under general anesthesia. Non-anatomic (wedge) resections are not permitted. Pathological specimens must contain a separately divided pulmonary artery and bronchus, as well as sampled lymph nodes from mediastinal lymph node stations. Participants found to have incidental nodal involvement after surgery will be referred for adjuvant chemotherapy, with our without postoperative radiotherapy.	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. Other Names: Lobectomy or Anatomic Segmentectomy

Arm

Intervention/Treatment

Experimental: Stereotactic radiotherapy

Stereotactic radiotherapy is an FDA approved treatment for lung cancer. However, for purposes of this study, it is being delivered to an operable population that is typically treated with surgical resection. Participants randomized to stereotactic radiotherapy will be treated according to the location of the tumor. Peripheral tumors will receive either 18 Gy x 3, 14 Gy x 4, or 11.5 Gy x 5 fractions, while central tumors will be treated with 10 Gy x 5. There will not be any elective coverage of local microscopic spread or regional lymph nodes.

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.

Other Names:

Stereotactic Body Radiation Therapy (SBRT) or Stereotactic Ablative Radiotherapy (SAbR)

Active Comparator: Surgery

Participants randomized to surgery will undergo a standard lobectomy or limited anatomic pulmonary resection (segmentectomy) under general anesthesia. Non-anatomic (wedge) resections are not permitted. Pathological specimens must contain a separately divided pulmonary artery and bronchus, as well as sampled lymph nodes from mediastinal lymph node stations. Participants found to have incidental nodal involvement after surgery will be referred for adjuvant chemotherapy, with our without postoperative radiotherapy.

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.

Other Names:

Lobectomy or Anatomic Segmentectomy

Outcome Measures

Primary Outcome Measures

Overall Survival [From date of randomization through study completion, up to 10 years]
Survival estimates will include death from any cause.

Secondary Outcome Measures

Patient reported health-related quality of life [5 years]
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.
Respiratory Function [5 years]
The St George's Respiratory Questionnaire will evaluate respiratory symptoms, activity limitations from breathlessness, and impact of respiratory function on social and psychological functioning.
Health State Utilities [5 years]
The EQ-5D-5L (EuroQOL-5D) survey will measure quality adjusted life years.
Lung cancer mortality [From date of randomization until date of death from any cause, assessed up to 10 years.]
Cause of death will be determined by an independent adjudication committee.
Tumor patterns of failure [5 years]
Post-treatment surveillance imaging will evaluate patients every 6 months for local, regional, and/or distant disease control.
Respiratory Function [5 years]
The Forced Expiratory Volume at 1 second (FEV1) will evaluate an objective measure of breathing function.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 an invasive malignancy within the past 5 years, whether newly diagnosed or recurrent, excluding low-risk prostate cancer, non-melanoma skin cancers, and in-situ cancers
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Long Beach Healthcare System, Long Beach, CA	Long Beach	California	United States	90822
2	Bay Pines VA Healthcare System, Pay Pines, FL	Bay Pines	Florida	United States	33744
3	Miami VA Healthcare System, Miami, FL	Miami	Florida	United States	33125
4	Edward Hines Jr. VA Hospital, Hines, IL	Hines	Illinois	United States	60141-5000
5	Richard L. Roudebush VA Medical Center, Indianapolis, IN	Indianapolis	Indiana	United States	46202-2884
6	Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD	Baltimore	Maryland	United States	21201
7	VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA	Boston	Massachusetts	United States	02130
8	VA Ann Arbor Healthcare System, Ann Arbor, MI	Ann Arbor	Michigan	United States	48105
9	Minneapolis VA Health Care System, Minneapolis, MN	Minneapolis	Minnesota	United States	55417
10	Durham VA Medical Center, Durham, NC	Durham	North Carolina	United States	27705
11	Louis Stokes VA Medical Center, Cleveland, OH	Cleveland	Ohio	United States	44106
12	Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA	Philadelphia	Pennsylvania	United States	19104
13	VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA	Pittsburgh	Pennsylvania	United States	15240
14	Michael E. DeBakey VA Medical Center, Houston, TX	Houston	Texas	United States	77030
15	Hunter Holmes McGuire VA Medical Center, Richmond, VA	Richmond	Virginia	United States	23249
16	Clement J. Zablocki VA Medical Center, Milwaukee, WI	Milwaukee	Wisconsin	United States	53295-1000

Sponsors and Collaborators

VA Office of Research and Development

Investigators

Study Chair: Drew Moghanaki, MD MPH, VA Greater Los Angeles Healthcare System, West Los Angeles, CA
Study Chair: David H Harpole, MD, Durham VA Medical Center, Durham, NC