Proton Beam Radiation for Rhabdomyosarcoma

Recruiting at 2 trial locations

Overseen By Torunn Yock, MD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must be taking: Chemotherapy

Disqualifiers: Pregnancy, Previous radiation, 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: 5

115 Participants Needed

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to see if using proton beam radiation therapy instead of photon beam radiation therapy can reduce side effects from radiation treatment for rhabdomyosarcoma. Photon beam radiation is the standard type of radiation for treating most rhabdomyosarcoma and many other types of cancer. Photon beam radiation enters the body and passes through healthy tissue, encounters the tumor, then leaves the body through healthy tissue. A beam of proton radiation enters the body and passes through healthy tissue, encounters tumor, but then stops. This means that less healthy tissue is affected by proton beam radiation than by photon beam radiation.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must be treated with a standardly accepted chemotherapy regimen.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must be treated with a standard chemotherapy regimen, so it's best to discuss your current medications with the trial team.

What data supports the idea that Proton Beam Radiation for Rhabdomyosarcoma is an effective treatment?

The available research shows that Proton Beam Radiation is effective for treating rhabdomyosarcoma, especially in young children. It suggests that this treatment can improve outcomes by reducing side effects compared to traditional radiation methods. For example, in cases of orbital rhabdomyosarcoma, Proton Beam Radiation helps avoid long-term functional and cosmetic side effects that are more common with conventional treatments. Additionally, studies indicate that Proton Beam Radiation is beneficial for tumors near critical areas like the head and neck, as it targets the tumor more precisely, sparing healthy tissue and potentially improving quality of life. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Proton Beam Radiation for Rhabdomyosarcoma?

Proton therapy for rhabdomyosarcoma in children, including infants, shows promise in improving outcomes by targeting tumors more precisely and reducing side effects compared to traditional radiation. Studies suggest it may be particularly beneficial for tumors near sensitive areas like the head and neck, helping to preserve normal tissue and improve quality of life. ^{1 2 3 4 5}

What safety data is available for proton beam therapy in treating rhabdomyosarcoma?

Proton beam therapy for rhabdomyosarcoma has been studied in various clinical settings. A multi-institutional study in Japan involving 55 pediatric patients showed that proton radiotherapy has similar treatment effects to photon radiotherapy with tolerable acute radiation-induced toxicity. The study reported 153 adverse events of Grade ≥3, primarily hematologic toxicities, but no proton-specific toxicity was observed. Other studies have focused on specific subtypes and age groups, indicating that proton therapy may improve the therapeutic ratio, especially in infants, and reduce long-term side effects compared to conventional photon therapy. ^{1 5 6 7 8}

Is proton beam radiation safe for humans?

Proton beam radiation has been used in children with rhabdomyosarcoma and is generally considered safe, with side effects similar to other radiation treatments. Most side effects were related to blood cell counts, and no specific harmful effects unique to proton therapy were observed. ^{1 5 6 7 8}

Is Proton Beam Radiation a promising treatment for Rhabdomyosarcoma?

Yes, Proton Beam Radiation is a promising treatment for Rhabdomyosarcoma. It helps target the cancer more precisely, which can reduce damage to healthy tissues and minimize side effects. This is especially beneficial for treating tumors near important organs, like in the head and neck areas. ^{1 4 9 10 11}

How is proton beam radiation different from other treatments for rhabdomyosarcoma?

Proton beam radiation is unique because it precisely targets tumors with minimal damage to surrounding healthy tissues, reducing long-term side effects compared to conventional radiation. This makes it particularly beneficial for treating rhabdomyosarcoma near critical structures like the head and neck. ^{1 4 9 10 11}

Research Team

Torunn Yock, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for children and young adults up to 21 years old with newly diagnosed rhabdomyosarcoma. They must be on a standard chemotherapy regimen and able to follow-up for five years post-treatment. It's not suitable for those with metastatic disease (except certain cases), previous radiation therapy, life-threatening co-morbidities, or if pregnant.

Inclusion Criteria

I am receiving a widely accepted chemotherapy treatment.

I am aged 2-10 with a specific type of cancer, allowing for metastatic disease.

Patients must be willing to receive follow-up care for a minimum of five years after treatment at MGH and annual visits unless it is too difficult to return to MGH for follow-up care. In that event, they must be willing to have their outside medical information released to us to track the results

Exclusion Criteria

I have health conditions that make radiation unsafe for me.

I have undergone radiation therapy before.

Life expectancy of less than 2 years

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Treatment

Participants receive proton beam radiation therapy once per day, 5 days a week for 4 to 6 weeks

4-6 weeks

5 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with further tests and evaluations for several years

4 years

Treatment Details

Interventions

• Proton Beam Radiation

Trial Overview The study tests proton beam radiation against the standard photon beam radiation in treating pediatric rhabdomyosarcoma. Proton radiation aims to minimize damage to healthy tissue by stopping at the tumor site rather than passing through it.

Participant Groups

Group I: Proton Beam Radiation Experimental Treatment 1 Intervention

Proton Beam Radiation

Proton Beam Radiation is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Proton Therapy for:

• Cancer of the brain and spinal cord
• Eye melanoma
• Head and neck cancers
• Breast cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer
• Prostate cancer

Approved in United States as Proton Beam Therapy for:

• Brain tumors
• Eye melanoma
• Head and neck cancers
• Breast cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer
• Prostate cancer
• Pediatric cancers

Approved in Japan as Proton Radiotherapy for:

• Brain tumors
• Eye melanoma
• Head and neck cancers
• Breast cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer
• Prostate cancer

Approved in Canada as Proton Therapy for:

• Brain tumors
• Eye melanoma
• Head and neck cancers
• Breast cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer
• Prostate cancer

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Brigham and Women's Hospital

Collaborator

Trials

1,694

Recruited

14,790,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Boston Children's Hospital

Collaborator

Trials

801

Recruited

5,584,000+

M.D. Anderson Cancer Center

Collaborator

Trials

3,107

Recruited

1,813,000+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Proton radiation therapy (PRT) was successfully used in two patients with orbital rhabdomyosarcoma, resulting in both being disease-free after 2.5 to 3.4 years, with excellent visual acuity and minimal cosmetic side effects.

PRT demonstrated superior sparing of critical normal tissues, such as the lens and pituitary gland, while effectively targeting the tumor, which may reduce the risk of long-term complications and second malignancies in childhood cancer survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractionated, three-dimensional, planning-assisted proton-radiation therapy for orbital rhabdomyosarcoma: a novel technique. Hug, EB., Adams, J., Fitzek, M., et al.[2019]

In a study of 66 children with nonmetastatic rhabdomyosarcoma treated with proton therapy, the 2-year local control rate was 88%, indicating that proton therapy is effective in managing this type of cancer.

All recurrences occurred within the treated radiation field, suggesting that the precise targeting of proton therapy does not increase the risk of marginal failures, even in patients with unfavorable risk features.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of Failure in Pediatric Rhabdomyosarcoma After Proton Therapy. Vern-Gross, TZ., Indelicato, DJ., Bradley, JA., et al.[2017]

In a study of 83 children with rhabdomyosarcoma treated with pencil beam scanning proton therapy, the 5-year overall survival rate was 80.6%, indicating effective treatment outcomes.

The treatment resulted in minimal late non-ocular toxicity (only 3.6% incidence of grade 3 toxicity) and improved quality of life scores after therapy, highlighting its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumour control and Quality of Life in children with rhabdomyosarcoma treated with pencil beam scanning proton therapy. Leiser, D., Calaminus, G., Malyapa, R., et al.[2022]

Rhabdomyosarcoma, the most common soft tissue sarcoma in children, has seen improved clinical outcomes due to enhanced treatment strategies developed by the Intergroup Rhabdomyosarcoma Study Group.

Advanced radiotherapy techniques, such as intensity-modulated radiotherapy and proton therapy, are being utilized to target tumors near critical structures, aiming to reduce radiation exposure and minimize long-term side effects while maintaining treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy for rhabdomyosarcoma: indications and outcome. Terezakis, SA., Wharam, MD.[2012]

In a study of 37 infants under 24 months with non-metastatic rhabdomyosarcoma treated with proton therapy, the 5-year local control, progression-free survival, and overall survival rates were 83%, 78%, and 83%, respectively, indicating promising outcomes for this age group.

Despite the young age being traditionally viewed as a negative prognostic factor, the results suggest that with appropriate local therapy, infants can achieve survival rates comparable to older children, although the classification of nasal ala as an unfavorable site may need reconsideration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton radiotherapy for infant rhabdomyosarcoma: Rethinking young age as an adverse prognostic factor. Parekh, AD., Indelicato, DJ., Vega, RBM., et al.[2021]

Proton radiotherapy (PRT) for pediatric patients with rhabdomyosarcoma (RMS) showed promising overall survival rates of 91.9% at 1 year and 84.8% at 2 years, with particularly high survival rates in low-risk groups (100%).

While there were 153 adverse events, mostly hematologic toxicities, proton-specific toxicity was not observed, indicating that PRT has a tolerable safety profile similar to traditional photon radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary results of proton radiotherapy for pediatric rhabdomyosarcoma: a multi-institutional study in Japan. Mizumoto, M., Murayama, S., Akimoto, T., et al.[2022]

In a study of 57 children with rhabdomyosarcoma treated with proton radiotherapy and chemotherapy, the five-year local control rate was 81%, with event-free survival at 69% and overall survival at 78%, indicating effective disease management.

The treatment was associated with low toxicity, as no acute or late adverse effects exceeded grade 3, suggesting that proton radiation is a safe option for pediatric patients compared to traditional photon radiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary results of a phase II trial of proton radiotherapy for pediatric rhabdomyosarcoma. Ladra, MM., Szymonifka, JD., Mahajan, A., et al.[2022]

Proton radiotherapy for children with parameningeal rhabdomyosarcoma (PM-RMS) resulted in a 5-year failure-free survival rate of 59% and an overall survival rate of 64%, indicating effective tumor control and survival outcomes comparable to historical controls.

The late side effects observed in patients treated with proton therapy, such as mild facial hypoplasia and dental issues, were fewer and less severe compared to those reported in patients treated with traditional photon therapy, suggesting a potentially safer profile for proton radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton radiotherapy for parameningeal rhabdomyosarcoma: clinical outcomes and late effects. Childs, SK., Kozak, KR., Friedmann, AM., et al.[2021]

Proton beam therapy is a viable option for urgent radiotherapy in children with parameningeal rhabdomyosarcoma that extends into the cranium, as demonstrated in a case series of 3 patients aged 6 to 12 years.

Timely transfer to facilities offering proton beam therapy can minimize delays in treatment, highlighting the importance of quick communication between hospitals when intracranial involvement is suspected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urgent Proton Beam Therapy With Interinstitutional Transfer for Patients With Intracranial Rhabdomyosarcoma: Report of 3 Cases. Inaba, M., Nakao, T., Hosaka, S., et al.[2021]

Proton beam therapy (PBT) was safely and effectively used to treat a 1-year-old girl with stage IV alveolar rhabdomyosarcoma, resulting in a 95% reduction in tumor volume after treatment, despite the tumor's challenging location and previous resistance to chemotherapy.

This case highlights the potential of PBT as a viable treatment option for pediatric patients with tumors that are difficult to manage with conventional radiotherapy, particularly when there are concerns about surrounding organ tolerance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton beam therapy for a patient with large rhabdomyosarcoma of the body trunk. Takizawa, D., Oshiro, Y., Mizumoto, M., et al.[2022]

In a study of 94 pediatric patients with rhabdomyosarcoma treated with proton beam therapy (PBT) and chemotherapy, the 4-year overall survival rate was 71% and the progression-free survival rate was 63%, indicating that PBT is an effective treatment option.

The study found that larger tumor size and delayed delivery of radiation therapy negatively impacted local control, progression-free survival, and overall survival, suggesting that timely treatment and possibly higher doses for larger tumors may improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disease Control and Patterns of Failure After Proton Beam Therapy for Rhabdomyosarcoma. Buszek, SM., Ludmir, EB., Grosshans, DR., et al.[2021]

References

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

Fractionated, three-dimensional, planning-assisted proton-radiation therapy for orbital rhabdomyosarcoma: a novel technique. [2019]

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

Patterns of Failure in Pediatric Rhabdomyosarcoma After Proton Therapy. [2017]

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

Tumour control and Quality of Life in children with rhabdomyosarcoma treated with pencil beam scanning proton therapy. [2022]

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

Radiotherapy for rhabdomyosarcoma: indications and outcome. [2012]

5. Ireland pubmed.ncbi.nlm.nih.gov

Proton radiotherapy for infant rhabdomyosarcoma: Rethinking young age as an adverse prognostic factor. [2021]

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

Preliminary results of proton radiotherapy for pediatric rhabdomyosarcoma: a multi-institutional study in Japan. [2022]

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

Preliminary results of a phase II trial of proton radiotherapy for pediatric rhabdomyosarcoma. [2022]

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

Proton radiotherapy for parameningeal rhabdomyosarcoma: clinical outcomes and late effects. [2021]

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

Urgent Proton Beam Therapy With Interinstitutional Transfer for Patients With Intracranial Rhabdomyosarcoma: Report of 3 Cases. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Proton beam therapy for a patient with large rhabdomyosarcoma of the body trunk. [2022]

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

Disease Control and Patterns of Failure After Proton Beam Therapy for Rhabdomyosarcoma. [2021]