Clinical trial NCT03673176: Lung Volume Reduction for Severe Emphysema by Stereotactic Ablative Radiation Therapy
Official title: Lung Volume Reduction for Severe Emphysema by Stereotactic Ablative Radiation Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Emphysema
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Varian, a Siemens Healthineers Company
First posted: 2018-09-17
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Since medical therapies offer only modest palliation and minimal hopes for improved survival to COPD patients, surgical therapies have been designed that may provide greater benefits in selected patients. Lung transplantation, for example, clearly improves survival and quality of life in patients with end stage COPD. This comes at substantial economic cost, however, as well as the at the cost of complications that may result from the complex surgery and from life-long immunosuppression. In addition, nearly all lung transplants will fail within 5 years as a result of progressive bronchiolitis obliterans, which we currently have no way to prevent or treat.

A second operation designed to treat severe COPD patients is lung volume reduction surgery (LVRS). This operation, designed for patients with predominant emphysema rather than chronic bronchitis, is among the most carefully studied operations ever developed.

We believe that by reducing the volume of emphysematous lung with the precise target localization made possible by image-guided SABR, that we will be able to duplicate the benefits of surgical lung volume reduction with far less risk. We believe that this may represent a major advance in the therapy of emphysema - a highly prevalent disease. It may provide not only palliation but also increased survival, as does surgical lung volume reduction, in carefully selected patients.

Detailed description: Stereotactic Ablative Radiotherapy (SABR), also called stereotactic body radiation therapy (SBRT), is a relatively recent advance in radiotherapy which allows high doses of radiation to be transmitted to focused areas (typically malignancies), allowing higher rates of tumoricidal activity, generally lower complications, and greater convenience for patients since it can be delivered in 1 to just a few sessions. As the radiation is administered from multiple directions according to stereotactic planning, high doses can be delivered to the tissues with rapid fall-off to relatively low doses in even nearby, surrounding normal tissues. This technique was initially applied to brain tumors- an application which over the years has met with great success. More recently, it has been applied with substantial success and is gaining increasing acceptance as a primary mode of therapy for stage I lung malignancies, and malignancies in multiple other body areas.

In the lung, the rate of pneumonitis resulting from SABR is far lower than the rates incurred by conventional external beam radiotherapy. In conventional external beam radiotherapy reported pneumonitis rates range from 13-37% (7), depending on dose and field size. Reported rates of symptomatic pneumonitis after lung SABR are significantly lower and generally are \~5% (8). SABR does, however, typically leave a scar in the area of lung that has been treated (9). Importantly, there appears to be contraction of surrounding lung parenchyma into this scar resulting in an effect that is essentially a "lung volume reduction." One often sees clear loss of lung volume following any form of lung radiotherapy. With SABR, this "volume reduction" is achieved with a far lower risk of morbidity - in particular, less risk of pneumonitis.

Eligibility criteria: Inclusion Criteria:

Pulmonary Function:

* Severe COPD with severe reduction in quality of life due to dyspnea
* Moderate to Severe emphysematous destruction of lung parenchyma on chest CT

  * FEV1 \< 45% predicted and \>18% predicted
  * FEV1/FVC \< .7
  * DLCO \> 18% predicted
  * Residual Volume \> 160% predicted (by plethysmography)

Arterial Blood Gas:

* paO2\>40 on room air at rest
* paCO2\<55

General:

* Successful completion of 16 sessions of pulmonary rehabilitation

Exclusion Criteria:

* Predominate chronic bronchitis (none or mild emphysematous destruction of lung on chest CT).
* Pulmonary function tests / lung volumes that do not meet above criteria.
* Active coronary ischemia (stress test required if clinical symptoms).
* Inability to complete 16 sessions of pulmonary rehabilitation.
* Pregnancy.
* Presence of lung cancer.

Primary outcomes:
measure: Count of Patients With Grade 3 or Higher Adverse Events.
timeFrame: 18 months
Secondary outcomes:
measure: Change From Baseline Value in Forced Expiratory Volume Percent Predicted
timeFrame: Baseline and months 6, 12, and 18
measure: Change From Baseline Value in Forced Expiratory Volume in 1 Second (Liters)
timeFrame: Baseline and months 6, 12, and 18
measure: Change From Baseline in Diffusing Capacity for Carbon Dioxide (% Predicted)
timeFrame: Baseline and months 6, 12, and 18
measure: Change From Baseline in 6 Minute Walk Test (Meters)
timeFrame: Baseline and month 6
measure: Total Lung Capacity (% of Predicted Value)
timeFrame: Baseline and date of last available time-point in follow-up period (up to 18 months)
measure: Residual Volume (RV) (% of Predicted Value)
timeFrame: Baseline and date of last available time-point in follow-up period (up to 18 months)
measure: Short Form (SF)-36 Quality of Life Survey Score
timeFrame: Baseline and months 6
measure: Modified Borg Dyspnea Scale
timeFrame: Baseline and months 6, 12, and 18
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford Cancer Center
state: California
Study officials:
affiliation: Stanford University
name: Joseph B Shrager, M.D
role: STUDY_DIRECTOR
References:
citation: Kamtam DN, Binkley MS, Kapula N, Sadeghi C, Nesbit S, Guo HH, Chang J, Maxim PG, Diehn M, Loo BW Jr, Shrager JB. First in Human Phase 1 Clinical Trial of Stereotactic Irradiation to Achieve Lung Volume Reduction (SILVR) in Severe Emphysema. Int J Radiat Oncol Biol Phys. 2024 Oct 1;120(2):345-356. doi: 10.1016/j.ijrobp.2024.03.049. Epub 2024 Apr 12.