FLASH Radiotherapy for Bone Metastases

(FAST-02 Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests FLASH radiotherapy, a new radiation treatment delivered at ultra-high speed, to determine if it can safely relieve pain from bone metastases in the chest area. Researchers aim to discover if this treatment causes fewer side effects than traditional radiation. Suitable participants have 1 to 3 painful bone metastases in the ribs, collarbones, shoulder blades, or breastbone area and have been informed they have more than six months to live. As an unphased trial, this study offers patients the chance to contribute to groundbreaking research in pain relief and cancer 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 prior data suggests that FLASH radiotherapy is safe for treating bone metastases?

Research has shown that FLASH radiotherapy holds promise for safety. In one study involving 10 patients with cancer spread to their bones, FLASH radiotherapy proved safe and practical. Another study found that side effects were mild and similar to those from regular radiation therapy, indicating that patients generally tolerate FLASH radiotherapy well. This treatment is unique because it delivers radiation rapidly, potentially shortening treatment times compared to standard methods. ^{1 2 3 4 5}

Why are researchers excited about this trial?

FLASH Radiotherapy is unique because it delivers radiation at ultra-high dose rates, unlike conventional treatments for bone metastases, which typically use standard dose rates. This technique aims to minimize damage to healthy tissues while targeting cancer cells more effectively. Researchers are excited about FLASH Radiotherapy because it has the potential to reduce side effects and improve the quality of life for patients, offering a promising new approach to managing painful bone metastases.

What evidence suggests that FLASH radiotherapy is effective for bone metastases?

Research has shown that FLASH radiotherapy, which uses very high doses of radiation, effectively relieves pain in cases of bone cancer spread. One study found that 67% of treated areas experienced pain relief, with 50% achieving complete pain relief, meaning no pain at all. Another trial confirmed the safety and effectiveness of this treatment for easing pain in patients with metastatic cancer. Participants in this trial will receive FLASH radiotherapy, which works faster than traditional methods and offers promising results for those with painful bone conditions. ^{1 2 4 6 7}

Who Is on the Research Team?

John Perentesis, MD

Principal Investigator

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

Are You a Good Fit for This Trial?

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)

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

Patients who are able to comply with the protocol

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10935811/

FLASH radiotherapy for the treatment of symptomatic bone ... FLASH therapy is an emerging form of radiation therapy (RT) in which radiation is delivered at ultra-high dose rates of at least 40 Gy/s.

2. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2797843

Proton FLASH Radiotherapy for the Treatment of ... In 8 of the 12 sites (67%) patients reported pain relief, and in 6 of the 12 sites (50%) patients reported a complete response (no pain).

3. sciencedirect.com sciencedirect.com/science/article/pii/S2405630825001399

First-in-human e-Flash radiotherapy using a modified ... The pulse repetition frequency was 200 Hz and pulse length 4.5 µs, which led to average and instantaneous dose rates of 216 Gy/s and 2.4·105 Gy/s, respectively.

4. astro.org astro.org/news-and-publications/news-and-media-center/news-releases/2022/flash-radiation-therapy-shows-promise-in-first-in-human-trial

FLASH radiation therapy shows promise in first-in-human trial Ultra-high dose-rate radiation treatment found safe and effective for pain relief in small trial of patients with metastatic cancer.

5. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/counter/pdf/10.1186/s13014-024-02419-4.pdf?utm_source=consensus

FLASH radiotherapy for the treatment of symptomatic bone ... FLASH therapy is an emerging form of radiation therapy. (RT) in which radiation is delivered at ultra-high dose rates of at least 40 Gy/s. Compared to RT given ...

6. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/pro6.70010

A safety study of ultra‐high dose rate FLASH radiotherapy ... Overall, the adverse events of proton FLASH-RT were mild and consistent with conventional RT. This group is conducting another clinical trial to ...

7. varian.com varian.com/about-varian/newsroom/press-releases/varian-completes-enrollment-and-treatment-fast-02-clinical

Varian Completes Enrollment and Treatment in FAST-02 ... Flash therapy delivers treatment at ultra-high dose rates in typically less than one second – over 100 times faster than conventional radiation ...