SABR for Oligometastatic Cancer

(SABR-COMET-3 Trial)

Recruiting at 17 trial locations

Overseen By Hadassah Abraham, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: British Columbia Cancer Agency

Must not be taking: Chemotherapy agents

Disqualifiers: Concurrent cancer, Poor lung function, 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

Duration: 2 weeks

330 Participants Needed

Trial Summary

What is the purpose of this trial?

Stereotactic Ablative Radiotherapy (SABR) is a modern RT technique that delivers high doses of radiation to small tumor targets using highly conformal techniques. SABR is non-invasive and delivered on an outpatient basis. The purpose of this study is to compare the effect of SABR, relative to standard of care (SOC) alone, on overall survival, progression-free survival, toxicity, and quality of life. An integrated economic evaluation will determine the cost per quality of life year gained using SABR (vs. SOC) and a translational component will enable identification of predictive/prognostic biomarkers of the oligometastatic state.

Will I have to stop taking my current medications?

The trial requires that you stop taking chemotherapy agents (drugs used to kill cancer cells) starting 2 weeks before radiation and until 1 week after the last treatment if you are in the SABR group.

What data supports the effectiveness of the treatment Stereotactic Ablative Body Radiotherapy (SABR) for oligometastatic cancer?

Research shows that SABR can improve survival rates and control cancer spread in patients with oligometastatic non-small cell lung cancer. It is also effective in controlling tumors in various organs with a high success rate, and may even be curative in some cases. ^{1 2 3 4 5}

Is SABR generally safe for treating oligometastatic cancer?

Stereotactic Ablative Body Radiotherapy (SABR) is generally considered safe for treating small lung tumors and oligometastases, with studies showing low toxicity levels. However, there are concerns about potential high-grade toxic effects and specific adverse effects like lung and chest wall issues, and rare cases of vertebral fractures. ^{2 6 7 8 9}

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

Stereotactic Ablative Radiotherapy (SABR) is unique because it delivers very precise, high doses of radiation directly to tumors while minimizing damage to nearby healthy organs. This noninvasive approach is emerging as a promising option for treating oligometastatic cancer, potentially offering high local control rates and even curative outcomes in some cases. ^{1 3 4 5 10}

Research Team

Robert Olson

Principal Investigator

BC Cancer Prince George

Eligibility Criteria

This trial is for adults with a limited number of cancer metastases (1-3 currently, up to 8 in their lifetime). They must have controlled primary tumors, be able to hold still during treatment, and not be pregnant. Excluded are those with concurrent cancers within the last 5 years, certain organ dysfunctions or large brain metastases.

Inclusion Criteria

I've had a brain scan within the last 8 weeks to check for cancer spread.

My primary cancer is under control.

I am 18 years old or older.

Exclusion Criteria

I need surgery to fix a bone in my thigh.

I have or had a tumor close to my spinal cord, but if removed, it's part of my 8 lifetime metastases limit.

Pregnant or breastfeeding women

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either standard of care palliative radiotherapy or stereotactic ablative radiotherapy (SABR) based on randomization

2 weeks

Multiple visits for radiotherapy sessions

Follow-up

Participants are monitored for safety, effectiveness, and quality of life post-treatment

5 years

Visits at 3 months, 6 months, and every 6 months for the first 2 years, then annually

Extension/Long-term follow-up

Participants may continue to be monitored for overall survival and progression-free survival

Long-term

Treatment Details

Interventions

• Palliative Radiotherapy
• Stereotactic Ablative Radiotherapy

Trial Overview The study compares Stereotactic Ablative Radiotherapy (SABR), a high-dose radiation therapy targeting small tumor areas non-invasively on an outpatient basis, against standard palliative care. It will assess survival rates, side effects, quality of life and cost-effectiveness.

Participant Groups

Group I: Stereotactic Arm (Arm 2) Experimental Treatment 1 Intervention

Stereotactic ablative radiotherapy, and chemotherapy at the discretion of the treating medical oncologist

Group II: Standard of Care Treatment (Arm 1) Active Control 1 Intervention

Standard of care, palliative radiotherapy, and chemotherapy at the discretion of the treating medical oncologist

Stereotactic Ablative Radiotherapy is already approved in European Union, United States, United Kingdom for the following indications:

Approved in European Union as Stereotactic Ablative Radiotherapy for:

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

Approved in United States as Stereotactic Ablative Radiotherapy for:

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

Approved in United Kingdom as Stereotactic Ablative Radiotherapy for:

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

Who Is Running the Clinical Trial?

British Columbia Cancer Agency

Lead Sponsor

Trials

181

Recruited

95,900+

Bon Secours Cork Cancer Centre

Collaborator

Trials

1

Recruited

330+

Walker Family Cancer Centre

Collaborator

Trials

1

Recruited

330+

Cancer Research UK Edinburgh Centre

Collaborator

Trials

2

Recruited

550+

UPMC Hillman Cancer Centre

Collaborator

Trials

1

Recruited

330+

Beatson West of Scotland Cancer Centre

Collaborator

Trials

3

Recruited

1,200+

Tom Baker Cancer Centre

Collaborator

Trials

30

Recruited

8,900+

Riverina Cancer Care Centre

Collaborator

Trials

1

Recruited

330+

London Regional Cancer Program, Canada

Collaborator

Trials

11

Recruited

1,300+

The Alfred

Collaborator

Trials

110

Recruited

10,030,000+

Findings from Research

In a study of 132 patients treated with single fraction stereotactic ablative body radiotherapy (SABR) for oligometastases, there was a 75% rate of freedom from widespread disease at 1 year, indicating effective disease control.

The treatment showed a high local control rate of 90% at 1 year and low toxicity, with only one case of significant treatment-related side effects, suggesting that single fraction SABR is a safe and effective option compared to traditional multi-fraction approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single Fraction Stereotactic Ablative Body Radiotherapy for Oligometastasis: Outcomes from 132 Consecutive Patients. Gandhidasan, S., Ball, D., Kron, T., et al.[2019]

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]

Stereotactic body radiation therapy (SBRT) is recommended as a safe and effective treatment for patients with oligometastatic non-small cell lung cancer, particularly when there are 3 or fewer metastatic deposits, based on a review of literature from 2008 to 2020.

The American Radium Society Lung Cancer Panel advises that consolidative radiation therapy should follow first-line systemic therapy rather than being administered upfront, and emphasizes the importance of individualized treatment plans due to limited data on certain clinical scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

American Radium Society Appropriate Use Criteria for Radiation Therapy in Oligometastatic or Oligoprogressive Non-Small Cell Lung Cancer. Amini, A., Verma, V., Simone, CB., et al.[2022]

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]

Stereotactic ablative radiotherapy (SABR) is a highly effective and low-toxicity treatment for metastatic tumors, achieving local control rates of about 80%.

SABR shows promise in treating oligometastatic patients, with pilot studies suggesting it may be 'curative' in 20-25% of cases, especially when combined with systemic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New concepts and insights into the role of radiation therapy in extracranial metastatic disease. Ricardi, U., Filippi, AR., Franco, P.[2013]

In a study of 39 patients with 45 lung lesions treated with stereotactic ablative body radiotherapy (SBRT), local progression-free survival rates were high, with 90.5% at 1 year and 80.5% at 2 years, indicating effective tumor control.

The treatment was well-tolerated with only mild acute side effects, suggesting that the moderate dose schedules of 35 Gy (5 fractions) or 37.5 Gy (3 fractions) are safe and effective for managing non-small cell lung cancer and metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy for small lung tumors with a moderate dose. Favorable results and low toxicity. Duncker-Rohr, V., Nestle, U., Momm, F., et al.[2022]

In a study of 381 patients treated with stereotactic ablative body radiotherapy (SABR) for oligometastatic disease, the incidence of grade 3 or higher toxic effects was found to be less than 5%, indicating a favorable safety profile.

The rates of grade 2 or higher toxic effects were 18.6%, which is lower than the previously reported 29% in the SABR-COMET trial, suggesting that SABR may have acceptable toxicity levels and supports further research in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment With Stereotactic Ablative Radiotherapy for Up to 5 Oligometastases in Patients With Cancer: Primary Toxic Effect Results of the Nonrandomized Phase 2 SABR-5 Clinical Trial. Olson, R., Jiang, W., Liu, M., 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]

A 68-year-old woman treated with stereotactic body radiation therapy (SBRT) for lung metastases experienced pathological vertebral fractures ten months post-treatment, highlighting a previously unreported adverse effect of SBRT.

Despite achieving a complete response of the metastatic disease without signs of radiation pneumonitis, the case emphasizes the need for oncologists to consider the risk of bone toxicity, particularly in older patients with potential low bone mineral density (BMD).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathological vertebral fracture after stereotactic body radiation therapy for lung metastases. Case report and literature review. Rodríguez-Ruiz, ME., San Miguel, I., Gil-Bazo, I., et al.[2022]

A single session of stereotactic ablative body radiotherapy (SABR) for oligometastatic prostate cancer was found to be feasible and safe, with only one significant adverse event (a vertebral fracture) reported among 33 patients over a 2-year follow-up period.

The treatment resulted in high local progression-free survival rates of 97% at 1 year and 93% at 2 years, with nearly half of the patients (48%) avoiding the need for androgen deprivation therapy at the 2-year mark, indicating effective disease control and maintained quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer: A Prospective Clinical Trial. Siva, S., Bressel, M., Murphy, DG., et al.[2022]

References

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

Single Fraction Stereotactic Ablative Body Radiotherapy for Oligometastasis: Outcomes from 132 Consecutive Patients. [2019]

2. 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]

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

American Radium Society Appropriate Use Criteria for Radiation Therapy in Oligometastatic or Oligoprogressive Non-Small Cell Lung Cancer. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

New concepts and insights into the role of radiation therapy in extracranial metastatic disease. [2013]

6. Germany pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy for small lung tumors with a moderate dose. Favorable results and low toxicity. [2022]

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

Treatment With Stereotactic Ablative Radiotherapy for Up to 5 Oligometastases in Patients With Cancer: Primary Toxic Effect Results of the Nonrandomized Phase 2 SABR-5 Clinical Trial. [2023]

8. 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]

9. England pubmed.ncbi.nlm.nih.gov

Pathological vertebral fracture after stereotactic body radiation therapy for lung metastases. Case report and literature review. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer: A Prospective Clinical Trial. [2022]