Stereotactic Radiotherapy for Lung Cancer

(ONE STOP Trial)

Overseen By Pamela Samson, M.D., MPHS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Disqualifiers: Past radiotherapy, Pregnant, Breastfeeding

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 1 day

10 Participants Needed

Trial Summary

What is the purpose of this trial?

Stereotactic body radiotherapy (SBRT) has become a standard of care for medically inoperable or high-risk operable early-stage non-small cell lung cancer (NSCLC) patients. It is also increasingly used to treat lung metastases in patients with oligometastatic disease. While SBRT is a powerful tool for the treatment of lung tumors, access to specialized treatment can be limited for patients who live far away from a treatment center. Geographic accessibility can be limiting even for patients receiving one fraction lung SBRT, as the typical consult, CT simulation, and one-fraction treatment workflow is typically at least two to three weeks from start to finish, with a minimum of three in-person appointments. In this study, a high-quality cone beam CT (CBCT) on-board imaging platform (HyperSight; Varian Medical Systems, Palo Alto, CA) will be coupled with advanced motion management and treatment techniques as well as Ethos (Varian Medical Systems, Palo Alto, CA) daily online adaptation to simulation-free workflow for one fraction SBRT. This has the potential to reduce the time it takes a patient to be cured of their lung tumor from two to three weeks to two to three hours. In this novel workflow, patients will undergo telephone/online consent followed by a diagnostic scan-based pre-plan for one fraction SBRT. On the morning of treatment, a brief follow-up appointment will be followed by treatment on the HyperSight/Ethos platform. Patients will be treated using a simulation-free workflow. A HyperSight Thorax Slow protocol CBCT will be acquired for study purposes, and then the patient will be treated with online adaptive CBCT-guided radiotherapy on the Ethos/HyperSight platform. Treatment delivery will take place following contouring and treatment planning. Patients will undergo standard of care simulation imaging in parallel for comparison. The purpose of this study is to evaluate the feasibility of a ONE fraction Simulation-free Treatment with CT-guided stereotactic adaptive radiotherapy for Oligometastatic and Primary lung tumors (ONE STOP) workflow for patients with small, peripheral primary or oligometastatic lung tumors.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Stereotactic Radiotherapy for Lung Cancer?

Research shows that stereotactic ablative radiotherapy (SABR) is effective for treating early-stage non-small cell lung cancer (NSCLC), offering tumor control and survival rates comparable to surgery for patients who cannot undergo surgery. SABR is also considered a superior option compared to conventional radiotherapy for inoperable lung cancer cases. ^{1 2 3 4 5}

Is stereotactic radiotherapy for lung cancer safe for humans?

Stereotactic radiotherapy, also known as SABR or SBRT, is generally safe for treating lung cancer, but it can cause some side effects, including potential damage to nearby structures. Most patients experience low levels of side effects, but some may have long-term management challenges due to radiological changes. ^{6 7 8 9 10}

How is stereotactic radiotherapy different from other treatments for lung cancer?

Stereotactic radiotherapy, also known as SABR or SBRT, is unique because it delivers high doses of radiation with great precision in just one or a few sessions, making it a noninvasive option for patients who cannot undergo surgery. It is particularly used for early-stage non-small cell lung cancer (NSCLC) and offers similar local control to surgery without the need for an operation. ^{1 3 5 11 12}

Research Team

Pamela Samson, M.D., MPHS

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for patients with early-stage non-small cell lung cancer or those with a few lung metastases who can't easily get to a treatment center. They must be able to give consent over the phone/online and have diagnostic scans suitable for planning their radiotherapy.

Inclusion Criteria

My tumor and body structure are suitable for a specific one-time radiation therapy.

Able to understand and willing to sign an IRB approved written informed consent

My tumor is located more than 2 cm away from the center of my chest.

Exclusion Criteria

I have had radiation in the same area where ONE STOP SBRT will be applied.

Pregnant and/or breastfeeding

Patient must have a negative pregnancy test within 14 days of ONE STOP SBRT

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (virtual)

Pre-treatment Planning

Participants undergo telephone/online consent followed by a diagnostic scan-based pre-plan for one fraction SBRT

1 day

1 visit (virtual)

Treatment

Participants receive one fraction SBRT using a simulation-free workflow with online adaptive CBCT-guided radiotherapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• One fraction stereotactic body radiotherapy

Trial Overview The study tests a new way of delivering stereotactic body radiotherapy (SBRT) using HyperSight/Ethos technology, which could shorten the treatment process from weeks to hours by eliminating certain steps like simulation.

Participant Groups

Group I: One Fraction SBRT Experimental Treatment 3 Interventions

Consenting and eligible patients will receive a prescription dose of 25-34 Gy in one fraction with adaptation based on daily anatomic changes as per clinical standard of care.

One fraction stereotactic body radiotherapy is already approved in United States, European Union, Japan for the following indications:

Approved in United States as SBRT for:

• Early-stage non-small cell lung cancer (NSCLC)
• Lung metastases in oligometastatic disease

Approved in European Union as SABR for:

• Early-stage NSCLC
• Lung metastases

Approved in Japan as SBRT for:

• Early-stage NSCLC
• Lung metastases

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Varian Medical Systems

Industry Sponsor

Trials

63

Recruited

3,700+

Dow R. Wilson

Varian Medical Systems

Chief Executive Officer since 2012

MBA from Dartmouth's Amos Tuck School of Business, BA from Brigham Young University

Dr. Deepak Khuntia

Varian Medical Systems

Chief Medical Officer since 2020

MD from the University of Cambridge, PhD from the University of Leicester

Findings from Research

Stereotactic ablative radiotherapy (SABR) is an effective treatment for early-stage non-small cell lung cancers (NSCLCs) that are medically inoperable, providing local control and toxicity levels comparable to surgical resection.

SABR is gaining interest as a noninvasive treatment option for patients with borderline resectable lung cancers, although further randomized studies are needed to evaluate its survival benefits in operable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy (SABR) for non-small cell lung cancer. Iyengar, P., Westover, K., Timmerman, RD.[2013]

Single-fraction stereotactic ablative radiotherapy (SABR) for early-stage lung cancer can be delivered with high precision using magnetic resonance (MR) guidance, achieving a mean gross tumor volume coverage of 99.6%.

While most patients completed the treatment in a single session, the study highlighted the need for better tracking of small tumors and reducing overall treatment times, as the median procedure lasted 120 minutes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delivery of magnetic resonance-guided single-fraction stereotactic lung radiotherapy. Finazzi, T., van Sörnsen de Koste, JR., Palacios, MA., et al.[2022]

In a multicenter phase 3 trial involving 101 patients with inoperable stage 1 non-small-cell lung cancer, stereotactic ablative body radiotherapy (SABR) demonstrated significantly better local control compared to standard radiotherapy, with a 68% reduction in the risk of local treatment failure (hazard ratio 0.32).

SABR was associated with a similar safety profile to standard radiotherapy, showing no increase in major toxicity, making it a preferred treatment option for patients with this type of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy versus standard radiotherapy in stage 1 non-small-cell lung cancer (TROG 09.02 CHISEL): a phase 3, open-label, randomised controlled trial. Ball, D., Mai, GT., Vinod, S., et al.[2022]

Stereotactic ablative body radiotherapy (SABR) is a significant advancement in radiotherapy that has been shown to improve tumor control and overall survival in patients with lung tumors.

The review highlights the current evidence supporting the efficacy of SABR for both primary and secondary lung tumors, along with ongoing trials that may further validate its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiotherapy (SABR) for primary and secondary lung tumours. Goldsmith, C., Gaya, A.[2022]

In a study of 100 patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic ablative body radiotherapy (SABR), the 1-, 2-, and 3-year local control rates were 100%, 93.55%, and 84.33%, respectively, indicating high efficacy in tumor control.

The treatment was associated with low toxicity, with only 2% of patients experiencing Grade-3 side effects, suggesting that SABR is a safe option for patients who are inoperable or refuse surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Definitive Treatment of Early-Stage Non-Small Cell Lung Cancer with Stereotactic Ablative Body Radiotherapy in a Community Cancer Center Setting. Heal, C., Ding, W., Lamond, J., et al.[2020]

The iSABR trial demonstrated that individualized stereotactic ablative radiotherapy (SABR) for lung tumors resulted in high local control rates, with freedom from local recurrence at 1 year ranging from 94% to 97% across different patient groups.

The trial showed a low incidence of severe toxic effects (only 5%), indicating that personalized dosing strategies can minimize risks while maintaining effective treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individualized Stereotactic Ablative Radiotherapy for Lung Tumors: The iSABR Phase 2 Nonrandomized Controlled Trial. Gensheimer, MF., Gee, H., Shirato, H., et al.[2023]

The TROG 13.01/ALTG 13.001 clinical trial is investigating the safety and efficacy of single versus multi-fraction stereotactic ablative body radiotherapy (SABR) for lung tumors in 84 patients with up to three metastases, aiming to determine the best treatment approach for pulmonary oligometastases.

The study will compare a single high dose of 28Gy to a total of 48Gy delivered in four fractions, assessing not only safety but also quality of life, survival rates, and potential cost implications of each treatment method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised phase II trial of Stereotactic Ablative Fractionated radiotherapy versus Radiosurgery for Oligometastatic Neoplasia to the lung (TROG 13.01 SAFRON II). Siva, S., Kron, T., Bressel, M., et al.[2022]

In a study of 102 patients treated with stereotactic ablative radiation therapy (SABR) for early-stage non-small-cell lung cancer, a significant correlation was found between higher Biological Equivalent Doses (BED) over 300 Gy and the development of radiological changes such as organizing pneumonia and lung affectation over a 2-year follow-up.

Radiological changes were more pronounced in patients receiving BEDs greater than 300 Gy to healthy lung volumes of at least 30 cc, suggesting that these findings could inform future radiotherapy dose constraints to minimize pulmonary toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological equivalent dose is associated with radiological toxicity after lung stereotactic ablative radiation therapy. Cases, C., Benegas, M., Sánchez, M., et al.[2023]

In a study of 40 patients with central and ultracentral non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR), those with ultracentral tumors experienced worse overall survival (OS) and progression-free survival (PFS) compared to those with central tumors, indicating a need for careful consideration in treatment planning.

The incidence of severe treatment-related toxicities (grade ≥3) was higher in the ultracentral group, with 12.5% of patients experiencing significant complications, including severe bronchial obstruction and esophageal perforation, highlighting the potential risks associated with SABR in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes in patients with central and ultracentral non-small cell lung cancer treated with stereotactic body radiotherapy: single-institution experience. Song, X., Zhao, L., Jiang, N., et al.[2023]

In a study of 300 patients with stage I non-small cell lung cancer treated with stereotactic ablative body radiotherapy (SABR), the treatment showed promising long-term local control and survival rates, with overall survival rates of 83% at 1 year and 37% at 4 years.

The treatment was associated with low toxicity, as no severe grade 4 or 5 adverse effects were reported, indicating that SABR is a safe and effective option for patients with this type of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long term outcome after 48 Gy stereotactic ablative body radiotherapy for peripheral stage I non-small cell lung cancer. Dubaere, E., Goffaux, M., Wanet, M., et al.[2020]

Stereotactic ablative body radiotherapy (SABR) is now the standard treatment for early-stage non-small-cell lung cancer (NSCLC) in patients who cannot undergo surgery, highlighting its efficacy in this patient population.

The review also discusses the safety profile of SABR, including reported toxicity rates, and explores its potential use in combination with other therapies for improved outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of outcomes following stereotactic ablative radiotherapy in the treatment of early-stage primary lung cancer. Murray, P., Franks, K., Hanna, GG.[2022]

The SABRTooth study aimed to assess the feasibility of a phase III randomized controlled trial comparing stereotactic ablative radiotherapy (SABR) to surgery for patients with stage I nonsmall cell lung cancer, but found that recruitment was challenging due to patients' treatment preferences.

Out of 318 patients considered, only 24 were randomized, with many preferring SABR over surgery, indicating that while SABR is a viable treatment option, more innovative study designs are needed to effectively evaluate its benefits compared to surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SABRTooth: a randomised controlled feasibility study of stereotactic ablative radiotherapy (SABR) with surgery in patients with peripheral stage I nonsmall cell lung cancer considered to be at higher risk of complications from surgical resection. Franks, KN., McParland, L., Webster, J., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy (SABR) for non-small cell lung cancer. [2013]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Delivery of magnetic resonance-guided single-fraction stereotactic lung radiotherapy. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy versus standard radiotherapy in stage 1 non-small-cell lung cancer (TROG 09.02 CHISEL): a phase 3, open-label, randomised controlled trial. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiotherapy (SABR) for primary and secondary lung tumours. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Definitive Treatment of Early-Stage Non-Small Cell Lung Cancer with Stereotactic Ablative Body Radiotherapy in a Community Cancer Center Setting. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Individualized Stereotactic Ablative Radiotherapy for Lung Tumors: The iSABR Phase 2 Nonrandomized Controlled Trial. [2023]

7. England pubmed.ncbi.nlm.nih.gov

A randomised phase II trial of Stereotactic Ablative Fractionated radiotherapy versus Radiosurgery for Oligometastatic Neoplasia to the lung (TROG 13.01 SAFRON II). [2022]

8. Ireland pubmed.ncbi.nlm.nih.gov

Biological equivalent dose is associated with radiological toxicity after lung stereotactic ablative radiation therapy. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Long-term outcomes in patients with central and ultracentral non-small cell lung cancer treated with stereotactic body radiotherapy: single-institution experience. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Long term outcome after 48 Gy stereotactic ablative body radiotherapy for peripheral stage I non-small cell lung cancer. [2020]

11. England pubmed.ncbi.nlm.nih.gov

A systematic review of outcomes following stereotactic ablative radiotherapy in the treatment of early-stage primary lung cancer. [2022]

12. England pubmed.ncbi.nlm.nih.gov

SABRTooth: a randomised controlled feasibility study of stereotactic ablative radiotherapy (SABR) with surgery in patients with peripheral stage I nonsmall cell lung cancer considered to be at higher risk of complications from surgical resection. [2022]