SABR for Metastatic Cancer

Overseen By Timothy Nguyen, M.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Must be taking: Hormone therapy

Disqualifiers: Interstitial lung disease, Crohn's, others

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

Compensation: Varies

Number of Visits: 8

Duration: 3 weeks

138 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase II/III international multicentre randomized trial. Patients will be randomized in a 1:2 ratio between the standard of care (Arm 1) and SABR (Arm 2) to all sites of disease. The study will start as a phase II trial with an opportunity to convert to a phase III trial. The objective of this trial is to determine the impact of SABR on overall survival, progression-free survival, quality of life, and toxicity in patients with polymetastatic disease.

Will I have to stop taking my current medications?

The trial requires that participants do not have plans for systemic therapy (like chemotherapy or immunotherapy) for 3 months from enrollment, but hormone therapy for breast or prostate cancer can be continued. The protocol does not specify other medication restrictions.

What data supports the effectiveness of the treatment SABR for metastatic cancer?

Research shows that SABR is effective in treating early-stage non-small cell lung cancer (NSCLC) and can improve outcomes for patients with pulmonary metastases. It offers precise, high-dose radiation treatment that is comparable to surgery in controlling tumors, especially for those who cannot undergo surgery. ^{1 2 3 4 5}

Is SABR generally safe for humans?

Stereotactic Ablative Body Radiotherapy (SABR) is generally considered safe for treating various cancers, including lung and liver cancers, though some serious complications have been reported. Most patients experience low rates of significant side effects, but strategies are needed to manage potential risks. ^{2 6 7 8 9}

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

SABR (Stereotactic Ablative Body Radiotherapy) is a unique treatment because it is a noninvasive approach that delivers highly focused radiation to tumors, minimizing damage to surrounding healthy tissue. This makes it particularly effective for treating small, localized metastases (spread of cancer) in various parts of the body, such as the lungs and bones, where traditional treatments might not be as precise. ^{1 2 3 4 10}

Eligibility Criteria

This trial is for adults with cancer that has spread to many places in the body, who can safely receive radiation therapy. They should not be planning any systemic treatments like chemotherapy for 3 months and must have a life expectancy of at least 6 months. Pregnant women or those with serious health issues related to radiotherapy are excluded.

Inclusion Criteria

Willing and able to provide informed consent

All my cancer areas can be safely targeted with radiation.

I am 18 years old or older.

Exclusion Criteria

Serious medical comorbidities precluding radiotherapy. These include interstitial lung disease in patients requiring thoracic radiation, Chrohn's disease in patients where the GI tract will receive radiotherapy, ulcerative colitis where the bowel will receive radiotherapy and connective tissue disorders such as lupus or scleroderma. For patients with liver metastases, moderate/severe liver dysfunction (Child-Pugh B or C). Substantial overlap with a previously treated radiation volume. Prior radiotherapy is allowed, as long as the composite plan meets dose constraints herein. For patients treated with radiation previously, biologically effective dose calculations should be used to equate previous doses to the tolerance doses listed in Appendix 1. All such cases must be discussed with the study PI. Inability to treat all sites of disease. Any brain metastasis >3 cm in size or a total volume of brain metastases greater than 30 cc. Solitary or dominant brian metastasis requiring surgical decompression. Radiologic evidence of spinal cord compression. Disseminated disease, including leptomeningeal metastases, peritoneal metastases/carcinomatosis, malignant pleural effusion, and lymphangitis carcinomatosis. Pregnant or lactating women.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SABR to all tumors, 6Gy x 5 over 3 weeks

3 weeks

5 visits (in-person)

Follow-up

Participants are monitored for progression-free survival, quality of life, and toxicity

5 years

Every 3 months for 2 years, then every 6 months until 5 years

Extension

Long-term follow-up for overall survival

5 years

Treatment Details

Interventions

• SABR
• Standard of Care

Trial Overview The ARREST-2 trial compares standard cancer care (Arm 1) with Stereotactic Ablative Radiotherapy (SABR) treatment (Arm 2). It aims to see if SABR improves survival, slows disease progression, enhances quality of life, and assesses its safety.

Participant Groups

Group I: SABR Active Control 1 Intervention

SABR to all tumors 6Gy x 5 over 3 weeks

Group II: Standard of Care Active Control 1 Intervention

Standard or care palliative radiotherapy (includes the option for no treatment)

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?

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Findings from Research

Stereotactic ablative body radiotherapy (SABR) is a feasible and well-tolerated treatment for patients with bone-only oligometastatic breast cancer, with 80% of patients successfully receiving treatment and no severe (grade 3 or 4) toxicities reported.

The treatment showed promising efficacy, with a 100% local progression-free survival (LPFS) and 67% distant progression-free survival (DPFS) at two years, suggesting that SABR could be a viable option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiotherapy (SABR) for bone only oligometastatic breast cancer: A prospective clinical trial. David, S., Tan, J., Savas, P., et al.[2020]

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]

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]

Stereotactic ablative radiation therapy (SABR) was found to be effective for treating pulmonary metastases, with a median follow-up of 23 months showing improved overall survival (OS) for patients with 3 or fewer metastases compared to those with more (74.2% vs. 59.3% at 24 months).

Patients with less responsive primary tumors (like adrenal or pancreatic cancers) had higher local failure rates, suggesting that higher doses of SABR or surgical options may be necessary for these cases to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiation therapy for pulmonary metastases: Improving overall survival and identifying subgroups at high risk of local failure. Pasalic, D., Lu, Y., Betancourt-Cuellar, SL., et al.[2021]

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 Body Radiotherapy (SABR) is an effective non-invasive treatment for small inoperable liver metastases, showing a high local control rate of 92% at 6 months and 57% at 1 and 2 years, with a median overall survival of 12 months for 19 patients studied.

The study found that higher doses (BED2 > 78 Gy) improved local control, particularly in smaller tumors (PTV sizes < 67 cm3), while maintaining low toxicity levels, with no acute toxicity greater than grade 2 and only one late toxicity incident reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated image-guided breath-hold SABR (stereotactic ablative body radiotherapy) of liver metastases--clinical results. Boda-Heggemann, J., Dinter, D., Weiss, C., et al.[2021]

The introduction of stereotactic ablative body radiotherapy (SABR) for stage I non-small-cell lung cancer (NSCLC) at a Scottish cancer center has led to improved median survival rates, increasing from 32.5 months before SABR was available to 48.8 months after its establishment.

SABR has not only improved survival outcomes but also increased the proportion of patients receiving radical therapy, particularly among younger and healthier patients, indicating its effectiveness as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Impact of SABR on Stage I Non-Small-Cell Lung Cancer Outcomes at a Scottish Cancer Centre. Stares, M., Lewis, G., Vallet, M., et al.[2023]

Stereotactic ablative radiotherapy (SABR) has rapidly expanded in clinical use for treating various primary and metastatic tumors, demonstrating promising results in tumor control.

Despite its effectiveness, SABR can lead to serious complications, highlighting the need for strategies to reduce these risks and improve the safety of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk. Lo, SS., Sahgal, A., Chang, EL., et al.[2018]

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]

Stereotactic ablative body radiotherapy (SABR) significantly improves overall survival in patients with stage I non-small cell lung cancer (NSCLC), with a hazard ratio of death of 0.69 compared to those receiving fractionated radiotherapy, indicating a 31% reduction in the risk of death.

In a study of 12,384 patients, those treated with SABR had a median overall survival of 715 days, compared to 648 days for those receiving fractionated radiotherapy, highlighting the efficacy of SABR as the standard of care for medically inoperable stage I NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Body Radiotherapy Versus Radical Radiotherapy: Comparing Real-World Outcomes in Stage I Lung Cancer. Phillips, I., Sandhu, S., Lüchtenborg, M., et al.[2020]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiotherapy (SABR) for bone only oligometastatic breast cancer: A prospective clinical trial. [2020]

2. 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]

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

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

4. Ireland pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiation therapy for pulmonary metastases: Improving overall survival and identifying subgroups at high risk of local failure. [2021]

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

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

6. England pubmed.ncbi.nlm.nih.gov

Hypofractionated image-guided breath-hold SABR (stereotactic ablative body radiotherapy) of liver metastases--clinical results. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Impact of SABR on Stage I Non-Small-Cell Lung Cancer Outcomes at a Scottish Cancer Centre. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk. [2018]

9. Ireland pubmed.ncbi.nlm.nih.gov

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

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

Stereotactic Ablative Body Radiotherapy Versus Radical Radiotherapy: Comparing Real-World Outcomes in Stage I Lung Cancer. [2020]