Stereotactic Ablative Radiotherapy for Oligometastatic Cancer

(TRITONS Trial)

Overseen By Tyler Seibert, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Tyler Seibert

Disqualifiers: Pregnancy, Interstitial lung disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

300 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. It might be best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Stereotactic Ablative Radiotherapy for Oligometastatic Cancer?

Stereotactic body radiotherapy (SBRT) is known for its excellent safety profile and is already an established treatment for stage I lung cancer, showing similar success rates to surgery. While evidence for its effectiveness in treating oligometastatic cancer is still limited, ongoing studies are exploring its potential benefits. ^{1 2 3 4 5}

Is Stereotactic Ablative Radiotherapy (SBRT) safe for treating oligometastatic cancer?

Stereotactic Ablative Radiotherapy (SBRT) is generally considered safe for treating oligometastatic cancer, with studies showing an excellent safety profile, especially when treating a single metastasis. However, safety data for treating multiple metastases is limited, and special considerations are needed for tumors in ultra-central locations. ^{2 3 5 6 7}

How is stereotactic ablative radiotherapy different from other treatments for oligometastatic cancer?

Stereotactic Ablative Radiotherapy (SBRT) is unique because it delivers high doses of radiation precisely to cancerous areas, minimizing damage to surrounding healthy tissue. This makes it particularly effective for treating small, localized areas of cancer (oligometastases) and is often used when surgery is not an option. ^{1 4 5 8 9}

What is the purpose of this trial?

This is a Phase III non-blinded randomized study evaluating patients with oligometastatic cancers (up to 10 metastases). Subjects are randomized 1:1 to stereotactic ablative radiotherapy (SABR) plus standard of care therapies versus SABR alone. The investigators will measure progression-free survival at 2 years based on the hypothesis that subjects treated with SABR plus standard of care will not experience disease progression for a longer period of time than subjects treated with standard of care alone. The investigators will also measure overall survival and safety of SABR, as well as biomarkers that may help predict, in the future, who will benefit from the SABR treatment.

Research Team

Tyler Seibert

Principal Investigator

University of California, San Diego

Eligibility Criteria

This trial is for adults with a confirmed solid malignancy and up to 10 metastases, excluding brain lesions. Participants must be healthy enough for standard therapy and SABR, willing to follow study procedures, and use effective contraception if applicable.

Inclusion Criteria

I have used effective birth control for at least a month and will continue during treatment.

I am using effective birth control methods during my treatment.

Provision of signed and dated informed consent form

Exclusion Criteria

I have a tumor larger than 5 cm or a brain tumor larger than 3 cm that hasn't been removed.

I haven't had radiation that would exceed safe levels in this study.

I have fluid buildup due to cancer in my chest or abdomen.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive stereotactic ablative radiotherapy (SABR) plus standard of care therapies or SABR alone

6-8 weeks

Follow-up

Participants are monitored for progression-free survival and toxicity

2 years

Treatment Details

Interventions

• Stereotactic Ablative Radiotherapy

Trial Overview The study compares the effectiveness of stereotactic ablative radiotherapy (SABR) combined with standard care versus SABR alone in prolonging the time patients live without disease progression. It's a Phase III trial where participants are randomly assigned to one of the two groups.

Participant Groups

Group I: SABR+SOC Experimental Treatment 1 Intervention

stereotactic ablative radiotherapy (SABR) plus standard of care (SOC) cancer therapy

Group II: SOC Active Control 1 Intervention

standard of care (SOC) cancer therapy

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?

Tyler Seibert

Lead Sponsor

Trials

1

Recruited

300+

Findings from Research

In a review of stereotactic body radiotherapy (SBRT) plans from 17 centers, it was found that 29% of patient plans compromised target volume coverage to meet organ-at-risk tolerances, highlighting the need for better plan quality metrics that do not rely solely on target coverage.

The study established that the prescription dose spillage (PDS) and modified gradient index (MGI) metrics provide updated guidance for evaluating SBRT plan quality, with PDS values aligning well with existing clinical trial constraints, while MGI values indicated discrepancies that need addressing for optimal treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-center evaluation of dose conformity in stereotactic body radiotherapy. Lee, J., Dean, C., Patel, R., et al.[2022]

In a study of 145 patients with multiple pulmonary metastases treated with stereotactic body radiotherapy (SBRT), the overall survival (OS) was 23.5 months, indicating that SBRT is effective for this condition.

The study found no increase in the risk of early death or severe toxicity (grade 4 or 5) associated with multiple SBRT treatments, suggesting a strong safety profile for this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy (SBRT) for multiple pulmonary oligometastases: Analysis of number and timing of repeat SBRT as impact factors on treatment safety and efficacy. Klement, RJ., Hoerner-Rieber, J., Adebahr, S., et al.[2018]

This phase 1 trial involving 39 eligible patients demonstrated that stereotactic body radiotherapy (SBRT) is safe for treating patients with 3 to 4 metastases or 2 metastases close together, with no treatment-related deaths reported.

Although no dose-limiting toxicities were observed, there were instances of late grade 3 adverse events, highlighting the importance of long-term follow-up for patients receiving SBRT for oligometastatic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Safety of Stereotactic Body Radiotherapy for the Treatment of Patients With Multiple Metastases: Findings From the NRG-BR001 Phase 1 Trial. Chmura, S., Winter, KA., Robinson, C., et al.[2023]

Stereotactic body radiotherapy (SBRT) is effective for treating stage I lung cancer, achieving local control rates similar to those of surgical resection while minimizing side effects to surrounding healthy tissues.

SBRT is being explored for treating oligometastatic disease, although current evidence of its clinical benefits is limited; ongoing international studies aim to clarify its effectiveness and potential combinations with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for oligometastatic disease. Hanna, GG., Landau, D.[2018]

In a study of 40 patients with EGFR wild-type oligometastatic non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT), the median overall survival was 40 months, indicating that SBRT can be an effective treatment option for this patient group.

The study found that high-dose radiation (BED10 ≥100 Gy) was associated with better progression-free survival compared to lower doses, and the treatment was well-tolerated, with no severe toxicities reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing efficacy and safety of stereotactic body radiation therapy for oligometastatic non-small cell lung cancer with epidermal growth factor receptor (EGFR) wild type. Hu, X., Li, H., Liu, H., et al.[2022]

In a study of 145 patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT), the treatment demonstrated a high local control rate with only 24.1% experiencing disease recurrence over a median follow-up of 65.6 months.

SBRT was associated with low toxicity, as only 3.4% of patients experienced grade 3 adverse events, and no patients suffered from severe (grade 4 or 5) toxicities, indicating that it is a safe treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year follow-up after stereotactic body radiotherapy for medically inoperable early-stage non-small cell lung cancer: a multicenter study. Guo, Y., Zhu, Y., Zhang, R., et al.[2023]

Stereotactic body radiotherapy (SBRT) for ultra-central lung tumors shows high efficacy, with pooled local control rates of 92% at 1 year and 89% at 2 years, based on a systematic review of 27 studies involving 1183 treated targets.

While SBRT is effective, it carries risks of severe toxicity, with a 6% incidence of grade 3-4 toxicities and a 4% incidence of treatment-related deaths, highlighting the importance of careful patient selection and treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for Ultra-Central lung Tumors: A systematic review and Meta-Analysis and International Stereotactic Radiosurgery Society practice guidelines. Yan, M., Louie, AV., Kotecha, R., et al.[2023]

Stereotactic body radiotherapy (SBRT) was safely implemented for 15 patients with early-stage lung cancer and lung oligometastases, achieving a high locoregional control rate of 93.3% after a median follow-up of 17 months.

The treatment involved careful planning and quality assurance, with doses ranging from 40 to 60 Gy delivered in 5-8 fractions, ensuring dosimetric accuracy and adherence to organ-at-risk constraints.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Setting up a lung stereotactic body radiotherapy service in a tertiary center in Eastern India: The process, quality assurance, and early experience. Shrimali, RK., Saha, A., Arun, B., et al.[2022]

In a phase II trial involving 26 patients with oligometastatic non-small-cell lung cancer (NSCLC), stereotactic body radiotherapy (SBRT) showed a 60% overall metabolic response rate, with 30% of patients achieving complete metabolic remission.

The treatment resulted in a median progression-free survival (PFS) of 11.2 months and an overall survival (OS) of 23 months, indicating that SBRT is an effective local treatment option for patients with limited metastatic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of stereotactic body radiotherapy to primary tumor and metastatic locations in oligometastatic nonsmall-cell lung cancer patients. Collen, C., Christian, N., Schallier, D., et al.[2022]

References

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

Multi-center evaluation of dose conformity in stereotactic body radiotherapy. [2022]

2. Ireland pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy (SBRT) for multiple pulmonary oligometastases: Analysis of number and timing of repeat SBRT as impact factors on treatment safety and efficacy. [2018]

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

Evaluation of Safety of Stereotactic Body Radiotherapy for the Treatment of Patients With Multiple Metastases: Findings From the NRG-BR001 Phase 1 Trial. [2023]

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

Stereotactic body radiotherapy for oligometastatic disease. [2018]

5. China pubmed.ncbi.nlm.nih.gov

Assessing efficacy and safety of stereotactic body radiation therapy for oligometastatic non-small cell lung cancer with epidermal growth factor receptor (EGFR) wild type. [2022]

6. China pubmed.ncbi.nlm.nih.gov

Five-year follow-up after stereotactic body radiotherapy for medically inoperable early-stage non-small cell lung cancer: a multicenter study. [2023]

7. Ireland pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for Ultra-Central lung Tumors: A systematic review and Meta-Analysis and International Stereotactic Radiosurgery Society practice guidelines. [2023]

8. India pubmed.ncbi.nlm.nih.gov

Setting up a lung stereotactic body radiotherapy service in a tertiary center in Eastern India: The process, quality assurance, and early experience. [2022]

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

Phase II study of stereotactic body radiotherapy to primary tumor and metastatic locations in oligometastatic nonsmall-cell lung cancer patients. [2022]