FLASH Radiotherapy for Bone Metastases

(FAST-02 Trial)

Recruiting at 1 trial location

Overseen By Jennifer Woo

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Varian, a Siemens Healthineers Company

Must not be taking: Cytotoxic chemotherapy

Disqualifiers: More than 3 metastases, Metal implants, Symptomatic pneumonitis, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

10 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess toxicities of FLASH radiotherapy treatment and pain relief in subjects with painful thoracic bone metastases. FLASH radiotherapy is radiation treatment delivered at ultra-high dose rates compared to conventional radiation treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have received certain chemotherapy or systemic therapy within 2 weeks before or 1 week after the planned radiation treatment.

What data supports the effectiveness of the treatment FLASH Radiotherapy for Bone Metastases?

Radiation therapy is known to effectively relieve pain and improve the quality of life for patients with bone metastases, and advanced techniques like stereotactic body radiation therapy (SBRT) and intensity-modulated radiation therapy (IMRT) have shown potential for excellent tumor control with minimal side effects. ^{1 2 3 4 5}

Is FLASH Radiotherapy safe for humans?

FLASH Radiotherapy has been shown in preclinical studies to reduce damage to healthy tissues compared to traditional radiation therapy, while still effectively treating tumors. However, most of the research has been done in animal models, and clinical application in humans is still very limited. ^{6 7 8 9 10}

How is FLASH Radiotherapy different from other treatments for bone metastases?

FLASH Radiotherapy is unique because it delivers radiation at an ultra-high dose rate in a very short time, which may reduce damage to healthy tissues compared to traditional methods that take longer to administer. ^{1 4 5 11 12}

Research Team

John Perentesis, MD

Principal Investigator

Medical Director Cincinnati Children's/UC Health Proton Therapy Center

Eligibility Criteria

Adults over 18 with 1-3 painful bone metastases in the thorax, expected to live more than 6 months, and can follow the study plan. Excluded are those with metal implants in the treatment area, prior radiation or therapy that affects tissue response to radiation within specific timeframes before/after treatment, pregnant or nursing women, and certain medical conditions.

Inclusion Criteria

Life expectancy >6 months (in the judgement of the investigator)

I am 18 years old or older.

My bone cancer can be targeted with a specific size of radiation treatment.

Exclusion Criteria

Patients with pacemakers or other implanted devices at risk of malfunction during radiotherapy

I haven't had any local treatments in the last 2 weeks that could affect pain assessment.

I cannot receive chest radiation due to health reasons.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive FLASH radiotherapy for painful bone metastases in the thorax

1 day

1 visit (in-person)

Follow-up

Participants are monitored for pain relief and toxicities post-treatment

6 months

Treatment Details

Interventions

• FLASH Radiotherapy

Trial Overview The trial is testing FLASH Radiotherapy for pain relief and safety in patients with painful bone metastases in the chest area. This new type of radiotherapy is given at much faster rates than conventional treatments.

Participant Groups

Group I: FLASH radiotherapy for painful bone metastasis(-es) Experimental Treatment 1 Intervention

FLASH radiotherapy is radiation treatment delivered at ultra-high dose rates compared to conventional radiation treatment.

FLASH Radiotherapy is already approved in United States for the following indications:

Approved in United States as FLASH Radiotherapy for:

• Symptomatic Bone Metastases

Who Is Running the Clinical Trial?

Varian, a Siemens Healthineers Company

Lead Sponsor

Trials

35

Recruited

7,200+

Findings from Research

In a study involving 327 patients with painful bone metastasis, single dose radiation therapy (RT) regimens of 6 Gy and 8 Gy showed significantly higher overall response rates (73% and 78%, respectively) compared to the 4 Gy regimen (59%).

The 8 Gy treatment group experienced the quickest pain relief, indicating it may be the optimal single fraction RT for this condition, although the 6 Gy regimen also produced similar efficacy, suggesting further research is needed to determine the best dosing strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial of three single-dose radiation therapy regimens in the treatment of metastatic bone pain. Jeremic, B., Shibamoto, Y., Acimovic, L., et al.[2019]

Radiation therapy (RT) significantly improves the quality of life (QoL) for patients with painful bone metastases, particularly by effectively controlling pain and reducing the need for pain medication, as shown in a study of 116 patients.

Both shorter (20 Gy/4-5 fractions) and longer (30 Gy/10 fractions) RT schemes provide similar improvements in QoL, indicating that shorter treatment regimens can be just as effective as longer ones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

To What Extent Does Radiotherapy Improve the Quality of Life of Patients With Bone Metastasis?: A Prospective, Single-Institutional Study. Arias, F., Arrarás, JI., Asín, G., et al.[2019]

In a study of 1880 patients receiving radiation therapy for bone metastases, 34.4% were found to have complicated cases, primarily due to pathological fractures and neurological issues.

Patients with complicated bone metastases were significantly less likely to receive single fraction radiation therapy (39.4%) compared to those with uncomplicated cases (70.4%), suggesting that SFRT utilization rates could be improved, with a recommended benchmark of at least 60%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and treatment patterns of complicated bone metastases in a population-based radiotherapy program. Tiwana, MS., Barnes, M., Yurkowski, E., et al.[2018]

A new expedited treatment method called STAT RAD allows patients with painful bone metastases to receive stereotactic body radiation therapy in one day, showing it is feasible and safe with doses up to 15 Gy.

In this study of 49 patients, 75% experienced pain relief by 8 weeks, but the effectiveness decreased over time, with a 16.7% retreatment rate at a median of 4.9 months, indicating a need for further research on dose escalation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

STAT RAD: Prospective Dose Escalation Clinical Trial of Single Fraction Scan-Plan-QA-Treat Stereotactic Body Radiation Therapy for Painful Osseous Metastases. Muller, DA., Wages, NA., Wilson, DD., et al.[2022]

Radiotherapy (RT) is an important treatment for spinal bone metastases, with studies showing that an 8 Gy single-fraction RT can effectively relieve pain, although optimal dosing for spinal cord compression remains unclear.

Advanced techniques like stereotactic body RT (SBRT) and intensity-modulated RT (IMRT) offer promising results in controlling tumors while reducing toxicity, making them suitable for localized cases or re-irradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current status and future of radiotherapy for spinal bone metastases. Ejima, Y., Matsuo, Y., Sasaki, R.[2018]

FLASH-RT delivers radiation at ultra-high dose rates (≥40 Gy/s), which significantly reduces damage to surrounding healthy organs while maintaining its effectiveness against tumors.

The rapid treatment time of FLASH-RT necessitates adjustments in the radiotherapy process, highlighting the need for careful planning and evaluation in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Key changes in the future clinical application of ultra-high dose rate radiotherapy. Lin, B., Fan, M., Niu, T., et al.[2023]

Ultra-high-dose rate FLASH radiotherapy (FLASH-RT) significantly reduces normal tissue damage while maintaining effectiveness in tumor treatment, comparable to conventional radiotherapy.

This review highlights the need for more research on ultra-high-dose rate X-ray irradiation, as most studies have focused on electron and proton beams, to fully explore its potential in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FLASH radiotherapy with photon beams. Montay-Gruel, P., Corde, S., Laissue, JA., et al.[2022]

FLASH radiotherapy (RT) delivers ultra-high dose rate radiation, which has been shown to reduce damage to healthy tissues while maintaining effective anti-cancer treatment, compared to traditional radiation therapy.

Current research primarily focuses on FLASH electrons, and for FLASH-RT to become a standard clinical practice, new technology for producing FLASH photon beams needs to be developed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FLASH radiotherapy: an emerging approach in radiation therapy. Matuszak, N., Suchorska, WM., Milecki, P., et al.[2022]

FLASH radiotherapy delivers ultra-high doses of radiation to tumors while significantly sparing healthy surrounding tissues, reducing potential side effects compared to conventional radiotherapy.

This innovative approach maintains effective anti-tumor action, suggesting a promising clinical potential for improving cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FLASH radiotherapy: What, how and why? Petersson, K.[2023]

Ultra-high dose rate (UHDR) radiation therapy, known as 'FLASH,' has shown promise in reducing normal tissue damage while effectively controlling tumors, with doses delivered at rates exceeding 40 Gy/s.

Pre-clinical studies indicate that FLASH therapy may enhance the therapeutic window for cancer treatment, leading to ongoing interdisciplinary research to explore its potential and address remaining questions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-high dose rate FLASH radiation therapy for cancer. Kim, MM., Zou, W.[2023]

Stereotactic body radiotherapy (SBRT) offers a promising treatment option for painful bone metastases, delivering high doses of radiation accurately over one to a few sessions, which may improve patient outcomes compared to conventional radiotherapy.

SBRT is particularly beneficial for treating tumors that are usually resistant to radiation, although it is important to consider potential toxicity to surrounding healthy tissues and the patterns of local treatment failures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy in the management of painful bone metastases. Jhaveri, P., Teh, BS., Bloch, C., et al.[2008]

This study involves 120 patients with spinal bone metastases receiving stereotactic body radiation therapy (SBRT) with different fractionation schedules to evaluate local tumor control and safety.

The trial aims to compare the effectiveness of SBRT with and without simultaneous integrated boost (SIB) in improving tumor targeting and patient outcomes, including pain relief and quality of life, over a follow-up period of three to six months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy with integrated-boost in patients with bone metastasis of the spine: study protocol for a randomized controlled trial. Sprave, T., Welte, SE., Bruckner, T., et al.[2023]

References

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

A randomized trial of three single-dose radiation therapy regimens in the treatment of metastatic bone pain. [2019]

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

To What Extent Does Radiotherapy Improve the Quality of Life of Patients With Bone Metastasis?: A Prospective, Single-Institutional Study. [2019]

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

Incidence and treatment patterns of complicated bone metastases in a population-based radiotherapy program. [2018]

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

STAT RAD: Prospective Dose Escalation Clinical Trial of Single Fraction Scan-Plan-QA-Treat Stereotactic Body Radiation Therapy for Painful Osseous Metastases. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

The current status and future of radiotherapy for spinal bone metastases. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Key changes in the future clinical application of ultra-high dose rate radiotherapy. [2023]

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

FLASH radiotherapy with photon beams. [2022]

8. Poland pubmed.ncbi.nlm.nih.gov

FLASH radiotherapy: an emerging approach in radiation therapy. [2022]

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

FLASH radiotherapy: What, how and why? [2023]

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

Ultra-high dose rate FLASH radiation therapy for cancer. [2023]

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

Stereotactic body radiotherapy in the management of painful bone metastases. [2008]

12. England pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy with integrated-boost in patients with bone metastasis of the spine: study protocol for a randomized controlled trial. [2023]