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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how Stereotactic Ablative Body Radiotherapy (SABR) affects the immune response in patients with early-stage lung cancer. Researchers are examining whether T-cells, a type of immune cell, can recognize and attack cancer cells following this treatment. People with stage I non-small cell lung cancer (NSCLC) who have a tumor suitable for biopsy and can receive SABR treatment might be suitable candidates. The goal is to determine if SABR treatment induces changes in the immune system that aid in fighting cancer. As an unphased trial, this study allows patients to contribute to groundbreaking research that could improve future cancer treatments.

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 prior data suggests that this protocol is safe for lung cancer patients?

Research has shown that stereotactic ablative radiotherapy (SABR) is usually well-tolerated by people with early-stage non-small cell lung cancer (NSCLC). Studies indicate that SABR has low rates of side effects and is considered safe and effective, especially for patients who may not be good candidates for surgery. This treatment uses precise, high-dose radiation to target tumors, protecting nearby healthy tissue. This precision makes SABR a safe option for treating early-stage lung cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of stereotactic ablative radiotherapy (SABR) for treating stage I non-small cell lung cancer (NSCLC) because it offers a highly precise way to target tumors. Unlike traditional radiation therapy, which can affect healthy surrounding tissue, SABR delivers concentrated doses of radiation directly to the tumor with pinpoint accuracy. This precision means fewer sessions are needed, potentially reducing side effects and improving patient comfort. Additionally, the post-SABR biopsy could provide valuable insights into the treatment's effectiveness and help tailor future therapies more precisely.

What evidence suggests that SABR is effective for stage I NSCLC?

Studies have shown that stereotactic ablative radiotherapy (SABR) effectively and safely treats early-stage non-small cell lung cancer (NSCLC). SABR is now the standard treatment for patients who cannot undergo surgery. Research indicates that SABR can precisely target and destroy lung tumors. Some studies have found that SABR provides excellent tumor control and survival rates similar to surgery. Overall, SABR is a promising option for those with early-stage lung cancer, especially when surgery isn't possible. Participants in this trial will receive SABR therapy and undergo a post-SABR biopsy to further evaluate treatment effects. ^{3 6 7 8 9}

Who Is on the Research Team?

Khinh Ranh Voong, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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 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 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]

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