Lung Volume Reduction for Severe Emphysema by Stereotactic Ablative Radiation Therapy

NCT ID: NCT03673176

Last Updated: 2024-07-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-11
• Study Completion Date: 2021-08-02

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.

Conditions

Emphysema

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Stereotactic Ablative Radiotherapy

Experimental stereotactic ablative radiation treatment

Group Type: EXPERIMENTAL

Stereotactic Ablative Radiotherapy (SABR)

Intervention Type: RADIATION

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

Interventions

Stereotactic Ablative Radiotherapy (SABR)

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

Intervention Type: RADIATION

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Varian, a Siemens Healthineers Company

INDUSTRY

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Joseph B. Shrager, MD

Professor and chief of thoracic surgery division

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joseph B Shrager, M.D

Role: STUDY_DIRECTOR

Stanford University

Locations

Stanford Cancer Center

Palo Alto, California, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 38615887 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

e-protocol 23203

Identifier Type: -

Identifier Source: org_study_id