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Lung Volume Reduction for Severe Emphysema by Stereotactic Ablative Radiation Therapy

Lung Volume Reduction for Severe Emphysema by Stereotactic Ablative Radiation Therapy

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03673176
Enrollment
9
Registered
2018-09-17
Start date
2013-02-11
Completion date
2021-08-02
Last updated
2024-07-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Emphysema

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.

Interventions

The prescribed dose will be 45 Gy in three fractions of 15 Gy, on each side that is treated.

Sponsors

Varian, a Siemens Healthineers Company
CollaboratorINDUSTRY
Stanford University
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

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.

Design outcomes

Primary

MeasureTime frameDescription
Count of Patients With Grade 3 or Higher Adverse Events.18 monthsAdverse events will be based upon National Cancer Institute Common Terminology Criteria

Secondary

MeasureTime frameDescription
Change From Baseline Value in Forced Expiratory Volume in 1 Second (Liters)Baseline and months 6, 12, and 18Forced Expiratory Volume will be taken both prior (baseline) and following the procedure (months 6, 12, and 18)
Change From Baseline in Diffusing Capacity for Carbon Dioxide (% Predicted)Baseline and months 6, 12, and 18Diffusing Capacity for Carbon Dioxide will be taken both prior (baseline) and following the procedure (months 6, 12, and 18)
Change From Baseline in 6 Minute Walk Test (Meters)Baseline and month 6The walk test will be done both prior (baseline) and following the procedure (month 6)
Change From Baseline Value in Forced Expiratory Volume Percent PredictedBaseline and months 6, 12, and 18Forced Expiratory Volume will be taken both prior (baseline) and following the procedure (months 6, 12, and 18)
Residual Volume (RV) (% of Predicted Value)Baseline and date of last available time-point in follow-up period (up to 18 months)Residual volume (RV) is the volume of air remaining in the lungs after maximum forceful expiration. In other words, it is the volume of air that cannot be expelled from the lungs, thus causing the alveoli to remain open at all times.
Short Form (SF)-36 Quality of Life Survey ScoreBaseline and months 6The SF-36 Physical Component Summary (PCS) assesses limitations in physical functioning due to health problems, limitations in usual role because of physical health problems, bodily pain, and general health perceptions; the mental component summary (MCS) assesses vitality, limitations in social functioning because of physical or emotional problems, limitations in usual role due to emotional problems, and general mental health. The PCS and MCS scores each range from 0 (worst) to 100 (best). Increases from baseline indicate improvement.
Modified Borg Dyspnea ScaleBaseline and months 6, 12, and 18This is a patient-reported scale to rate the difficulty of breathing. The scale ranges from 0 to 10, wherein 0 indicates no difficulty breathing, and 10 indicates a maximal difficulty in breathing. Patients may report in whole numbers, from 0 to 10, in addition to reporting 0.5, which indicates very, very slight (just noticeable) difficulty in breathing. A negative change in score indicates a reduction in patient-reported breathing difficulty. The greater the negative change, the better the patient-reported breathing.
Total Lung Capacity (% of Predicted Value)Baseline and date of last available time-point in follow-up period (up to 18 months)Total Lung Capacity will be measured both prior (baseline) and following the procedure (up to 18 months)

Countries

United States

Participant flow

Pre-assignment details

9 participants signed consent; 8 were allocated to the study arm.

Participants by arm

ArmCount
Stereotactic Ablative Radiotherapy
Stereotactic Ablative Radiotherapy (SABR): 45 Gy in three fractions of 15 Gy, on each side that is treated.
8
Total8

Withdrawals & dropouts

PeriodReasonFG000
Overall StudyDeath following intervention3
Overall StudyDeath prior to intervention1
Overall StudyWithdrawal by Subject1

Baseline characteristics

CharacteristicStereotactic Ablative Radiotherapy
Age, Continuous73.0 years
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
7 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
1 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
Race (NIH/OMB)
Asian
1 Participants
Race (NIH/OMB)
Black or African American
0 Participants
Race (NIH/OMB)
More than one race
0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
Race (NIH/OMB)
Unknown or Not Reported
1 Participants
Race (NIH/OMB)
White
6 Participants
Region of Enrollment
United States
8 Participants
Sex: Female, Male
Female
1 Participants
Sex: Female, Male
Male
7 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
4 / 9
other
Total, other adverse events
3 / 9
serious
Total, serious adverse events
4 / 9

Outcome results

Primary

Count of Patients With Grade 3 or Higher Adverse Events.

Adverse events will be based upon National Cancer Institute Common Terminology Criteria

Time frame: 18 months

Population: Participants who received SABR

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Stereotactic Ablative RadiotherapyCount of Patients With Grade 3 or Higher Adverse Events.3 Participants
Secondary

Change From Baseline in 6 Minute Walk Test (Meters)

The walk test will be done both prior (baseline) and following the procedure (month 6)

Time frame: Baseline and month 6

Population: Participants with available data

ArmMeasureGroupValue (MEDIAN)
Stereotactic Ablative RadiotherapyChange From Baseline in 6 Minute Walk Test (Meters)Baseline289.0 meters
Stereotactic Ablative RadiotherapyChange From Baseline in 6 Minute Walk Test (Meters)6 months406.0 meters
Stereotactic Ablative RadiotherapyChange From Baseline in 6 Minute Walk Test (Meters)Change at 6 months27.0 meters
Secondary

Change From Baseline in Diffusing Capacity for Carbon Dioxide (% Predicted)

Diffusing Capacity for Carbon Dioxide will be taken both prior (baseline) and following the procedure (months 6, 12, and 18)

Time frame: Baseline and months 6, 12, and 18

Population: Participants who received SABR and with data at each respective time point

ArmMeasureGroupValue (MEDIAN)
Stereotactic Ablative RadiotherapyChange From Baseline in Diffusing Capacity for Carbon Dioxide (% Predicted)Baseline40.0 percentage of predicted value
Stereotactic Ablative RadiotherapyChange From Baseline in Diffusing Capacity for Carbon Dioxide (% Predicted)Change at 6 months-8.0 percentage of predicted value
Stereotactic Ablative RadiotherapyChange From Baseline in Diffusing Capacity for Carbon Dioxide (% Predicted)Change at 12 months-10.0 percentage of predicted value
Stereotactic Ablative RadiotherapyChange From Baseline in Diffusing Capacity for Carbon Dioxide (% Predicted)Change at 18 months-3.5 percentage of predicted value
Secondary

Change From Baseline Value in Forced Expiratory Volume in 1 Second (Liters)

Forced Expiratory Volume will be taken both prior (baseline) and following the procedure (months 6, 12, and 18)

Time frame: Baseline and months 6, 12, and 18

Population: Participants who received SABR and with data at each respective time point

ArmMeasureGroupValue (MEDIAN)
Stereotactic Ablative RadiotherapyChange From Baseline Value in Forced Expiratory Volume in 1 Second (Liters)Baseline0.79 liters
Stereotactic Ablative RadiotherapyChange From Baseline Value in Forced Expiratory Volume in 1 Second (Liters)Change at 6 months0.13 liters
Stereotactic Ablative RadiotherapyChange From Baseline Value in Forced Expiratory Volume in 1 Second (Liters)Change at 12 months0.14 liters
Stereotactic Ablative RadiotherapyChange From Baseline Value in Forced Expiratory Volume in 1 Second (Liters)Change at 18 months0.02 liters
Secondary

Change From Baseline Value in Forced Expiratory Volume Percent Predicted

Forced Expiratory Volume will be taken both prior (baseline) and following the procedure (months 6, 12, and 18)

Time frame: Baseline and months 6, 12, and 18

Population: Participants who received SABR and with data at each respective time point

ArmMeasureGroupValue (MEDIAN)
Stereotactic Ablative RadiotherapyChange From Baseline Value in Forced Expiratory Volume Percent PredictedBaseline28.5 percentage of predicted value
Stereotactic Ablative RadiotherapyChange From Baseline Value in Forced Expiratory Volume Percent PredictedChange at 6 months5.0 percentage of predicted value
Stereotactic Ablative RadiotherapyChange From Baseline Value in Forced Expiratory Volume Percent PredictedChange at 12 months3.0 percentage of predicted value
Stereotactic Ablative RadiotherapyChange From Baseline Value in Forced Expiratory Volume Percent PredictedChange at 18 months5.5 percentage of predicted value
Secondary

Modified Borg Dyspnea Scale

This is a patient-reported scale to rate the difficulty of breathing. The scale ranges from 0 to 10, wherein 0 indicates no difficulty breathing, and 10 indicates a maximal difficulty in breathing. Patients may report in whole numbers, from 0 to 10, in addition to reporting 0.5, which indicates very, very slight (just noticeable) difficulty in breathing. A negative change in score indicates a reduction in patient-reported breathing difficulty. The greater the negative change, the better the patient-reported breathing.

Time frame: Baseline and months 6, 12, and 18

Population: Data were not collected for this outcome measure

Secondary

Residual Volume (RV) (% of Predicted Value)

Residual volume (RV) is the volume of air remaining in the lungs after maximum forceful expiration. In other words, it is the volume of air that cannot be expelled from the lungs, thus causing the alveoli to remain open at all times.

Time frame: Baseline and date of last available time-point in follow-up period (up to 18 months)

Population: Participants who received SABR and with data at last available time-point in follow-up period

ArmMeasureGroupValue (MEDIAN)
Stereotactic Ablative RadiotherapyResidual Volume (RV) (% of Predicted Value)Baseline191 percentage of predicted value
Stereotactic Ablative RadiotherapyResidual Volume (RV) (% of Predicted Value)Last available time-point in follow-up period188 percentage of predicted value
Secondary

Short Form (SF)-36 Quality of Life Survey Score

The SF-36 Physical Component Summary (PCS) assesses limitations in physical functioning due to health problems, limitations in usual role because of physical health problems, bodily pain, and general health perceptions; the mental component summary (MCS) assesses vitality, limitations in social functioning because of physical or emotional problems, limitations in usual role due to emotional problems, and general mental health. The PCS and MCS scores each range from 0 (worst) to 100 (best). Increases from baseline indicate improvement.

Time frame: Baseline and months 6

Population: Participants who received SABR and with data at each respective time point

ArmMeasureGroupValue (MEDIAN)
Stereotactic Ablative RadiotherapyShort Form (SF)-36 Quality of Life Survey ScorePCS-Baseline31.9 score on a scale
Stereotactic Ablative RadiotherapyShort Form (SF)-36 Quality of Life Survey ScorePCS-6 months24.9 score on a scale
Stereotactic Ablative RadiotherapyShort Form (SF)-36 Quality of Life Survey ScoreMCS-baseline48.0 score on a scale
Stereotactic Ablative RadiotherapyShort Form (SF)-36 Quality of Life Survey ScoreMCS-6 months51.5 score on a scale
Secondary

Total Lung Capacity (% of Predicted Value)

Total Lung Capacity will be measured both prior (baseline) and following the procedure (up to 18 months)

Time frame: Baseline and date of last available time-point in follow-up period (up to 18 months)

Population: Participants who received SABR and with data at last available time-point in follow-up period

ArmMeasureGroupValue (MEDIAN)
Stereotactic Ablative RadiotherapyTotal Lung Capacity (% of Predicted Value)Baseline127.5 percentage of predicted value
Stereotactic Ablative RadiotherapyTotal Lung Capacity (% of Predicted Value)Last available time-point in follow-up period119.5 percentage of predicted value

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026