Post-SABR Biopsy for Lung Cancer

Overseen By Ranh Voong, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Immunotherapy, Steroids, Chemotherapy, others

Disqualifiers: Prior thoracic radiation, Pregnancy, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

6 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot be on steroids within 14 days before radiation and until after the post-SABR biopsies and blood samples. You also cannot be on any investigational agents, chemotherapy, or immunotherapy.

What data supports the effectiveness of the treatment Post-SABR Biopsy for Lung Cancer?

Research shows that stereotactic ablative body radiotherapy (SABR) is effective in controlling tumors and improving survival in patients with early-stage non-small cell lung cancer (NSCLC), especially for those who cannot undergo surgery. SABR is a precise form of radiation therapy that delivers high doses of radiation to the tumor, and it is considered a standard treatment for medically inoperable lung cancers. ^{1 2 3 4 5}

Is Stereotactic Ablative Body Radiotherapy (SABR) generally safe for treating lung cancer?

Stereotactic Ablative Body Radiotherapy (SABR) is generally safe for treating lung cancer, but it can cause some side effects, including chest wall pain and rib fractures. The risk of serious side effects is low, but larger tumors may have more toxicity. ^{6 7 8 9 10}

How is the treatment SABR different from other treatments for lung cancer?

Stereotactic Ablative Body Radiotherapy (SABR) is a unique treatment for lung cancer because it delivers highly focused radiation doses to the tumor with precision, minimizing damage to surrounding healthy tissue. This approach is particularly beneficial for patients who are not suitable for surgery, offering improved tumor control and survival rates. ^{1 3 11 12 13}

What is the purpose of this trial?

This is a pilot study to compare pre- and post-SABR core biopsies of stage I NSCLC tumors to identify SABR-induced immune-mediated tumor recognition based on a significant and specific expansion of T-cell clones using a novel T-cell receptor (TCR) sequencing assay. This will be coupled with (1) novel genomic analysis of candidate tumor antigens that may be released from the pre-SABR tumor and (2) functional validation assays to screen post-treatment peripheral blood T-cells for reactivity to these released candidate tumor antigens. In addition, cell-based analysis will be used to identify changes in key T-cell infiltrates into the post-SABR tumor.

Research Team

Khinh Ranh Voong, MD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

Adults over 18 with Stage I non-small cell lung cancer that can be treated with SABR and biopsied are eligible. They must have normal organ function, not be pregnant, and agree to follow the study protocol. Excluded are those on steroids close to radiation treatment, prior thoracic radiation in the same area, or current chemotherapy/immunotherapy.

Inclusion Criteria

I am older than 18 years.

I am post-menopausal or not currently pregnant.

My organs and bone marrow are functioning well.

Exclusion Criteria

My primary tumor cannot be repeatedly biopsied.

I am not currently taking any experimental drugs or chemotherapy.

I haven't used steroids 14 days before or during my radiation treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-SABR Biopsy

Participants undergo a pre-SABR biopsy as part of standard care

1 week

1 visit (in-person)

SABR Treatment

Participants receive stereotactic ablative radiotherapy (SABR)

1 week

1 visit (in-person)

Post-SABR Biopsy

Participants undergo a post-SABR biopsy to assess immune response

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Multiple visits (in-person and virtual)

Treatment Details

Interventions

• Post-SABR Biopsy
• SABR

Trial Overview The trial is testing how stage I NSCLC tumors respond immunologically to a type of targeted radiotherapy called SABR by examining T-cell changes before and after treatment using advanced genomic analysis techniques.

Participant Groups

Group I: Stage I NSCLC with SABR Therapy Experimental Treatment 1 Intervention

Participants receive stereotactic ablative radiotherapy (SABR) and pre-SABR biopsy as part of standard of care and then receive a post-SABR biopsy after receiving SABR.

SABR is already approved in European Union, United States, United Kingdom for the following indications:

Approved in European Union as SABR for:

• Early-stage non-small cell lung cancer
• Liver cancers
• Kidney cancers
• Bone metastasis
• Spinal metastasis
• Prostate cancers

Approved in United States as SABR for:

• Early-stage non-small cell lung cancer
• Liver cancers
• Kidney cancers
• Bone metastasis
• Spinal metastasis
• Prostate cancers

Approved in United Kingdom as SABR for:

• Early-stage non-small cell lung cancer
• Liver cancers
• Kidney cancers
• Bone metastasis
• Spinal metastasis
• Prostate cancers

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Findings from Research

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 phase 2 trial involving 40 patients with early-stage non-small cell lung cancer (NSCLC), neoadjuvant stereotactic ablative radiotherapy (SABR) resulted in a pathologic complete response (pCR) rate of 60%, indicating a significant tumor response but lower than expected.

The combined approach of neoadjuvant SABR followed by surgery showed no perioperative mortality and manageable toxicity, with a 2-year overall survival rate of 77%, suggesting it is a safe option for patients fit for surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring the Integration of Stereotactic Ablative Radiotherapy Plus Surgery for Early-Stage Non-Small Cell Lung Cancer: A Phase 2 Clinical Trial. Palma, DA., Nguyen, TK., Louie, AV., et al.[2022]

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]

Stereotactic body radiation therapy (SBRT) is a preferred treatment for early-stage non-small cell lung cancer (NSCLC) patients who cannot undergo surgery, but accurate lymph node staging is crucial for optimal patient selection.

Current staging methods like PET/CT and EBUS have limited sensitivity in detecting lymph node metastases, which can lead to undetected cancer spread and poorer outcomes; thus, invasive staging procedures are often necessary to improve detection and potentially enhance survival with adjuvant therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Undetected lymph node metastases in presumed early stage NSCLC SABR patients. Cerra-Franco, A., Diab, K., Lautenschlaeger, T.[2017]

In a study of 53 patients with lung tumors ≥5 cm treated with SABR, 30% experienced severe toxicity (grade ≥3), highlighting the need for improved treatment planning to reduce risks.

Using a knowledge-based planning model, researchers found that nearly 50% of the treatment plans for patients with severe toxicity could have been improved, particularly in terms of lung dose exposure, suggesting that model-based quality assurance could enhance safety in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Knowledge-Based Planning for Identifying High-Risk Stereotactic Ablative Radiation Therapy Treatment Plans for Lung Tumors Larger Than 5 cm. Hof, SV., Delaney, AR., Tekatli, H., et al.[2019]

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]

Stereotactic ablative radiation therapy (SABR) for lung oligometastases shows promising safety and efficacy, with a 24-month overall survival rate of 74.6% and minimal toxicity, as only one significant adverse event was reported among 77 patients studied over an average follow-up of 22 months.

Colorectal metastases exhibited a notably higher local failure rate compared to other types of tumors, suggesting they may be more resistant to SABR, indicating a need for potential dose escalation strategies for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colorectal Histology Is Associated With an Increased Risk of Local Failure in Lung Metastases Treated With Stereotactic Ablative Radiation Therapy. Binkley, MS., Trakul, N., Jacobs, LR., et al.[2022]

In a study of 500 patients treated with stereotactic ablative body radiotherapy (SABR) for stage I non-small cell lung cancer, severe chest wall pain (CWP) occurred in only 2% of patients, indicating that serious toxicity is rare with this treatment.

The study found that larger treatment volumes and closer tumor-chest wall distances were associated with increased risk of CWP and rib fractures, suggesting that careful planning of radiation doses can help minimize these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and risk factors for chest wall toxicity after risk-adapted stereotactic radiotherapy for early-stage lung cancer. Bongers, EM., Haasbeek, CJ., Lagerwaard, FJ., 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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

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

Measuring the Integration of Stereotactic Ablative Radiotherapy Plus Surgery for Early-Stage Non-Small Cell Lung Cancer: A Phase 2 Clinical Trial. [2022]

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

Response evaluation after stereotactic ablative radiotherapy for localised non-small-cell lung cancer: an equipoise of available resource and accuracy. [2021]

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

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

5. England pubmed.ncbi.nlm.nih.gov

Undetected lymph node metastases in presumed early stage NSCLC SABR patients. [2017]

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

Knowledge-Based Planning for Identifying High-Risk Stereotactic Ablative Radiation Therapy Treatment Plans for Lung Tumors Larger Than 5 cm. [2019]

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

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

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

Colorectal Histology Is Associated With an Increased Risk of Local Failure in Lung Metastases Treated With Stereotactic Ablative Radiation Therapy. [2022]

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

Incidence and risk factors for chest wall toxicity after risk-adapted stereotactic radiotherapy for early-stage lung cancer. [2022]

10. Ireland pubmed.ncbi.nlm.nih.gov

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

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

Follow-up of patients after stereotactic radiation for lung cancer: a primer for the nonradiation oncologist. [2022]

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

Patterns of disease recurrence after stereotactic ablative radiotherapy for early stage non-small-cell lung cancer: a retrospective analysis. [2022]

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

Optimal imaging surveillance after stereotactic ablative radiation therapy for early-stage non-small cell lung cancer: Findings of an International Delphi Consensus Study. [2018]