SBRT for Oligo-Progressive Cancer

(RADIANT Trial)

Overseen By Srinivas Raman

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Must be taking: ADT, Docetaxel

Disqualifiers: ≥6 metastases, Spinal cord compression, 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: 8

Duration: Duration not specified

130 Participants Needed

Trial Summary

What is the purpose of this trial?

Systemic therapy is the main treatment for patients with metastatic cancers. Oligo-progression has become a recognized entity for metastatic cancer and it is thought that a subset of cancer cells may develop heterogeneity and resistant clones while receiving systemic therapy. This results in overall tumor response but progression in metastatic sites. Current standard is to change systemic therapies. With advancing technologies, stereotactic body radiation therapy is being used to deliver high doses of focused radiation to the disease site, while minimizing risk of injury to the surrounding organs. SBRT is increasingly being used in patients presenting oligo-metastatic disease, and is recognized as having a potential for cure. This study will investigate the use of SBRT for breast and genito-urinary cancer patients with oligo-progression. Patients will be seen before and at the end of treatment and will be followed at 4 month intervals for up to 2 years. During the visits participants will complete quality of life questionnaires and will have standard of care imaging. Patients will also have the option to provide blood at baseline, during treatment, and at various follow up time points for analysis of ctDNA

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, it mentions that patients with oligo-progressive disease should have been receiving systemic therapy for at least 3 months, suggesting that continuing some treatments might be allowed.

What data supports the effectiveness of the treatment Stereotactic Body Radiotherapy (SBRT) for oligo-progressive cancer?

Research suggests that SBRT can improve progression-free and overall survival in patients with oligometastatic non-small cell lung cancer. It is also shown to have high local control rates and low toxicity, potentially delaying the need for systemic therapy changes and improving quality of life. ^{1 2 3 4 5}

Is Stereotactic Body Radiotherapy (SBRT) generally safe for humans?

Stereotactic Body Radiotherapy (SBRT), also known as Stereotactic Ablative Radiotherapy (SABR), is generally considered safe, but some serious complications have been reported. Studies have shown that while it is effective in controlling tumors, there are concerns about high-grade toxic effects, especially in certain types of cancer or tumor locations. Strategies to reduce these risks are important to ensure a favorable balance between benefits and potential side effects. ^{6 7 8 9 10}

How is SBRT different from other treatments for oligo-progressive cancer?

SBRT (Stereotactic Body Radiotherapy) is unique because it delivers very precise, high doses of radiation directly to tumors while minimizing damage to nearby healthy tissues. This approach can effectively control tumor growth with low toxicity and may delay the need to change systemic therapies, potentially improving survival and quality of life for patients with oligo-progressive cancer. ^{1 4 5 11 12}

Eligibility Criteria

This trial is for adults with certain types of cancer, like breast or genitourinary cancers, who have a small number (5 or less) of progressing tumors despite systemic therapy. Participants must be able to consent and have at least one tumor that can be treated with SBRT. They should not have had prior radiotherapy that overlaps with the treatment area or any conditions listed in the exclusion criteria.

Inclusion Criteria

My cancer has grown by at least 5 mm while on treatment, as shown on two scans 2-3 months apart.

My cancer is confirmed to be in the genitourinary tract.

My cancer has spread to 5 or fewer places in or outside my brain.

Exclusion Criteria

My cancer is not neuroendocrine, lymphoma, myeloma, or germ cell.

I do not have a current blockage in my intestines.

I cannot handle the physical setup needed for SBRT.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive stereotactic body radiation therapy (SBRT) for oligo-progressive malignancies

Duration not specified

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits every 4 months for up to 2 years

24 months

6 visits (in-person)

Treatment Details

Interventions

• Stereotactic Body Radiotherapy

Trial Overview The study is testing Stereotactic Body Radiotherapy (SBRT) on patients with oligo-progressive metastatic disease—meaning their cancer has spread but only a few areas are getting worse while on standard treatments. The goal is to see if high-dose radiation focused on these few areas can control the disease without harming nearby organs.

Participant Groups

Group I: Oligo-metastatic Breast Cancer Experimental Treatment 1 Intervention

Receiving SBRT.

Group II: Oligo-Progression; GU Experimental Treatment 1 Intervention

Receiving SBRT.

Stereotactic Body Radiotherapy is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Stereotactic Body Radiation Therapy for:

• Lung cancer
• Liver cancer
• Spine tumors
• Pancreatic cancer
• Prostate cancer

Approved in United States as Stereotactic Body Radiation Therapy for:

• Early-stage lung cancer
• Liver cancer
• Spine tumors
• Pancreatic cancer
• Prostate cancer

Approved in Canada as Stereotactic Body Radiation Therapy for:

• Lung cancer
• Liver cancer
• Spine tumors
• Pancreatic cancer
• Prostate cancer

Approved in Japan as Stereotactic Body Radiation Therapy for:

• Lung cancer
• Liver cancer
• Spine tumors
• Pancreatic cancer
• Prostate cancer

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

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]

Stereotactic ablative radiotherapy (SABR) was found to be a safe and effective treatment for women with oligometastatic or progressive gynecological cancers, with a median progression-free survival (PFS) of 10.8 months based on a study of 28 patients and 47 lesions.

Favorable treatment responses were associated with smaller tumor sizes and higher biologically effective doses, indicating that careful patient selection and treatment planning can enhance the effectiveness of SABR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes for Stereotactic Ablative Radiotherapy in Oligometastatic and Oligoprogressive Gynecological Malignancies. Mesko, S., Sandler, K., Cohen, J., et al.[2018]

Stereotactic body radiation therapy (SBRT) demonstrated a high local control rate of 86.8% at one year and 76.3% at two years in treating oligometastatic disease in elderly patients, with a median age of 79 years and 82 patients involved in the study.

The treatment was found to be safe, with only 4.2% of patients experiencing Grade 2-3 toxicity and 5.9% experiencing Grade 1 toxicity, indicating that SBRT is a viable option for elderly patients, especially those who are fragile or prefer to avoid more invasive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of stereotactic body radiation therapy (SBRT) in the treatment of oligometastatic disease in the elderly. Scorsetti, M., Clerici, E., Navarria, P., et al.[2018]

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 body radiotherapy (SBRT) is effective in treating metastatic cancer, particularly in cases of oligometastatic disease and oligoprogression, where it targets progressing tumors while other tumors remain stable.

SBRT offers high local control rates with low toxicity, potentially delaying the need for systemic therapy and improving patients' progression-free survival and quality of life, although more prospective clinical trials are needed to confirm these benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for oligoprogressive cancer. Cheung, P.[2018]

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 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]

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 40 patients with central and ultracentral non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR), those with ultracentral tumors experienced worse overall survival (OS) and progression-free survival (PFS) compared to those with central tumors, indicating a need for careful consideration in treatment planning.

The incidence of severe treatment-related toxicities (grade ≥3) was higher in the ultracentral group, with 12.5% of patients experiencing significant complications, including severe bronchial obstruction and esophageal perforation, highlighting the potential risks associated with SABR in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes in patients with central and ultracentral non-small cell lung cancer treated with stereotactic body radiotherapy: single-institution experience. Song, X., Zhao, L., Jiang, N., et al.[2023]

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 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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Clinical Outcomes for Stereotactic Ablative Radiotherapy in Oligometastatic and Oligoprogressive Gynecological Malignancies. [2018]

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

The role of stereotactic body radiation therapy (SBRT) in the treatment of oligometastatic disease in the elderly. [2018]

4. 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]

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

Stereotactic body radiotherapy for oligoprogressive cancer. [2018]

6. 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]

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

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

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

Long-term outcomes in patients with central and ultracentral non-small cell lung cancer treated with stereotactic body radiotherapy: single-institution experience. [2023]

11. Netherlands pubmed.ncbi.nlm.nih.gov

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

12. Germany pubmed.ncbi.nlm.nih.gov

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