SABR for Metastatic Cancer

Overseen By David Palma, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

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

Must be taking: Hormone therapy

Must not be taking: Cytotoxic agents

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: Unknown

48 Participants Needed

Trial Summary

What is the purpose of this trial?

Stereotactic ablative radiotherapy (SABR) is a new radiation treatment that delivers high-dose, precise radiation to small areas in the body. This new technique can potentially allow radiation treatments to be focused more precisely, and be delivered more accurately than with older treatments. This improvement could help by reducing side effects overall (through radiation exposure to a smaller area of the body over a shorter time period), and by improving the chance of controlling the cancer by more precisely treating the cancer and by giving higher doses of radiation. SABR is considered a standard treatment for some lung cancers, and selected cancers that have spread to the brain. Ongoing studies are evaluating the use of SABR for treating people with up to 10 sites of cancer in the body, but its safety and value for treating patients with poly-metastatic cancer (more than 10 sites of cancer) is not yet known. The purpose of this study is to determine the safety of using SABR to treat people with poly-metastatic disease. To our knowledge, this is the first time that SABR will be tested in people who have poly-metastatic disease.

Will I have to stop taking my current medications?

You may need to stop taking certain medications. Cytotoxic, immunotherapeutic, or molecularly targeted agents are not allowed starting 2 weeks before radiation. However, you can continue hormone therapies like anti-estrogen or anti-testosterone treatments.

What data supports the effectiveness of the treatment Stereotactic ablative radiotherapy for metastatic cancer?

Research shows that stereotactic ablative radiotherapy (SABR) can improve survival in patients with a small number of metastases from cancers like breast, colorectal, prostate, and lung, compared to standard palliative radiation. It has been associated with longer overall and progression-free survival, indicating its potential effectiveness for treating metastatic cancer. ^{1 2 3 4 5}

Is SABR generally safe for treating metastatic cancer?

Stereotactic ablative radiotherapy (SABR) has been used safely in treating various cancers, including lung and liver metastases, with studies showing low levels of acute and late toxicity. However, very high doses for central lung tumors can lead to significant side effects, so dose adjustments are important to minimize risks. ^{6 7 8 9 10}

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

Stereotactic ablative radiotherapy (SABR) is a unique treatment for metastatic cancer because it delivers highly focused radiation doses to tumors with precision, minimizing damage to surrounding healthy tissue. This approach is particularly beneficial for patients with limited metastatic sites (oligometastatic disease) and has shown promising results in improving survival rates and reducing local failure in various cancers. ^{3 5 11 12 13}

Research Team

Glenn Bauman, MD

Principal Investigator

London Health Sciences Centre, Lawson Health Research Institute

Eligibility Criteria

This trial is for adults with poly-metastatic cancer, meaning they have more than 10 sites of cancer in their body. They should not be pregnant or breastfeeding, must have a life expectancy over 3 months, and cannot start new systemic therapies within 6 weeks after radiotherapy. Patients with severe liver or kidney dysfunction, large brain metastases, or certain medical conditions that preclude radiotherapy are excluded.

Inclusion Criteria

My cancer has spread, and this was confirmed by tests.

Spine: MRI of the spine is not mandatory for enrollment.

My doctor believes all my cancer sites can be safely treated.

Exclusion Criteria

I have signs of pressure on my spinal cord.

My cancer has spread to the brainstem.

My liver is not working well due to cancer spread.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive stereotactic ablative radiotherapy (SABR) to treat poly-metastatic disease

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years and 3 months

Long-term follow-up

Participants are monitored for progression-free survival post radiotherapy

4 years

Treatment Details

Interventions

• Stereotactic ablative radiotherapy - De-escalation Level
• Stereotactic ablative radiotherapy - Level 1
• Stereotactic ablative radiotherapy - Level 2
• Stereotactic ablative radiotherapy - Level 3
• Stereotactic ablative radiotherapy - Level 4

Trial Overview The ARREST study tests the safety of Stereotactic Ablative Radiotherapy (SABR) on patients with poly-metastatic disease. SABR delivers high-dose radiation precisely to small areas and may reduce side effects by limiting exposure to healthy tissue. This phase I trial will determine if it's safe for those who have widespread cancer beyond what's currently treated with SABR.

Participant Groups

Group I: Dose Level 4 Experimental Treatment 1 Intervention

Group II: Dose Level 3 Experimental Treatment 1 Intervention

Group III: Dose Level 2 Experimental Treatment 1 Intervention

Group IV: Dose Level 1 Experimental Treatment 1 Intervention

Group V: De-escalation Level Experimental Treatment 1 Intervention

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+

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

Lead Sponsor

Trials

668

Recruited

424,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Ontario Institute for Cancer Research

Collaborator

Trials

24

Recruited

9,200+

Findings from Research

In a phase II trial involving 106 patients with metastatic cancers, the combination of ipilimumab and stereotactic ablative radiotherapy (SABR) showed promising long-term survival rates, with 5-year overall survival rates of 15%.

Patients receiving SABR targeting lung metastases had significantly better overall survival (18.67 months) and progression-free survival (6.87 months) compared to those with liver metastases, highlighting the importance of tumor location in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year overall survival with ipilimumab and stereotactic ablative radiotherapy for metastatic disease. He, K., Hong, DS., Tang, C., et al.[2023]

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) using Cyberknife demonstrated high effectiveness in treating stage I non-small-cell lung cancer, with 2-year local control, progression-free, and overall survival rates of 91.9%, 61.7%, and 84.8%, respectively, based on a study of 153 patients.

The treatment was generally safe, with only 8.1% of patients experiencing severe toxicities, including one case of grade 5 radiation pneumonitis, indicating that while SABR is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. Hayashi, K., Suzuki, O., Shiomi, H., et al.[2022]

A consensus document was created by trial management groups from six UK studies on stereotactic ablative radiotherapy (SABR) to establish updated organ at risk dose constraints, enhancing safety during treatment.

This unified approach aims to standardize the implementation of SABR across the UK, enabling better comparisons of toxicity and efficacy between different SABR studies both nationally and internationally.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

UK Consensus on Normal Tissue Dose Constraints for Stereotactic Radiotherapy. Hanna, GG., Murray, L., Patel, R., et al.[2022]

Stereotactic ablative radiotherapy (SABR) shows high effectiveness for oligometastatic breast cancer, achieving local control rates of 97% at 1 year and 90% at 2 years, based on a meta-analysis of 10 studies involving 467 patients.

SABR is associated with a low toxicity rate, with only 4.1% of patients experiencing grade 2 or 3 side effects, indicating it is a safe treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy to treat breast cancer oligometastases: A systematic review with meta-analysis. Viani, GA., Gouveia, AG., Louie, AV., et al.[2021]

Stereotactic ablative radiotherapy (SABR) demonstrated a high local control rate of 91.2% for skeletal metastases in a study of 22 patients, with a median follow-up of 15.6 months, indicating its effectiveness in managing oligometastatic and oligoprogressive diseases.

The treatment resulted in significant pain control for two-thirds of symptomatic patients, with limited toxicities reported, including only two vertebral fractures and one case of grade 3 esophagitis, suggesting that SABR is a safe option for patients with skeletal metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utilization of stereotactic ablative radiotherapy in oligometastatic & oligoprogressive skeletal metastases: Results and pattern of failure. Kam, TY., Chan, OSH., Hung, AWM., et al.[2019]

References

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

Feasible Optimization of Stereotactic Ablative Radiotherapy Dose by Tumor Size for Stage I Non-small-cell Lung Cancer. [2019]

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

SABR Combats Metastatic Disease. [2019]

3. Ireland pubmed.ncbi.nlm.nih.gov

Five-year overall survival with ipilimumab and stereotactic ablative radiotherapy for metastatic disease. [2023]

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

Stereotactic ablative radiotherapy for the comprehensive treatment of 1-3 Oligometastatic tumors (SABR-COMET-3): study protocol for a randomized phase III trial. [2020]

5. 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]

6. Greece pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. [2022]

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

UK Consensus on Normal Tissue Dose Constraints for Stereotactic Radiotherapy. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

BOMB trial: First results of stereotactic radiotherapy to primary breast tumor in metastatic breast cancer patients. [2023]

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

A Phase I Dose-Escalation Trial of Single-Fraction Stereotactic Radiation Therapy for Liver Metastases. [2022]

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

Stereotactic ablative body radiotherapy for lung cancer. [2018]

11. Ireland pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy to treat breast cancer oligometastases: A systematic review with meta-analysis. [2021]

12. Australia pubmed.ncbi.nlm.nih.gov

Utilization of stereotactic ablative radiotherapy in oligometastatic & oligoprogressive skeletal metastases: Results and pattern of failure. [2019]

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

Stereotactic Ablative Body Radiotherapy for Lung Metastases: Where is the Evidence and What are We Doing With It? [2022]