Proton + Standard Radiation Therapy for Sarcoma

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Northwestern University

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Metastatic disease, Active infection, Hypertension, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 58

28 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I/II trial studies the side effects and best dose of proton-spatially fractionated radiotherapy (P-SFRT) and to see how well it works with standard radiation therapy in treating patients with newly diagnosed retroperitoneal soft tissue sarcoma. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Standard spatially fractionated radiotherapy (SFRT) refers to how the radiation is delivered to the tumor. SFRT means that different parts of the tumor are receiving different doses of radiation (fractionation) through beams that allow areas of higher and lower (peaks and valleys) of doses of the radiation. This spatial fractionation allows an overall high-dose radiation to be given in the peaks and those areas of the tumor may release cells and substances that may help with killing tumor cells, reducing tumor symptoms and shrinking tumors. Proton therapy is a type of radiation therapy that can overcome some of the barriers of standard SFRT. Protons are tiny radioactive particles that can be controlled in a beam to travel up to the tumor and, compared to the particles used in standard radiotherapy, proton therapy can deliver higher doses to the tumor because smaller doses of radiation are delivered to tissues away from the tumor. This allows radiation therapy dose-escalated (continuously increasing the dose of radiation) treatment to tumors even though the tumor is near radiation sensitive organs like the colon. Giving P-SFRT with standard radiation therapy may work better in treating patients with newly diagnosed retroperitoneal soft tissue sarcoma.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had chemotherapy, radiotherapy, or other cancer treatments within 28 days before starting the trial, and you should not have taken steroids or immunosuppressive therapy within 7 days before the trial begins.

What data supports the effectiveness of the treatment Proton + Standard Radiation Therapy for Sarcoma?

Research shows that proton therapy can target tumors more precisely, reducing damage to nearby healthy tissues. This precision may improve treatment outcomes for sarcomas, which are a type of cancer that can be difficult to treat with standard radiation alone. ^{1 2 3 4 5}

Is proton therapy safe for treating sarcomas?

Proton therapy is generally considered safe for treating sarcomas, as it can reduce radiation exposure to healthy tissues, potentially lowering the risk of side effects. Studies have shown that it can limit both immediate and long-term toxicities, with only a few cases of severe side effects reported. ^{5 6 7 8 9}

What makes Proton + Standard Radiation Therapy for Sarcoma unique compared to other treatments?

Proton + Standard Radiation Therapy for Sarcoma is unique because it combines proton therapy, which can precisely target tumors while sparing surrounding healthy tissues, with spatially fractionated radiotherapy (GRID therapy), which is designed to treat large, bulky tumors that are difficult to manage with conventional methods. This combination may offer improved tumor control and reduced side effects, especially in cases where traditional radiation is not feasible due to the proximity of critical organs. ^{1 3 4 5 10}

Research Team

Seth M. Pollack

Principal Investigator

Northwestern University

Eligibility Criteria

This trial is for individuals with newly diagnosed retroperitoneal soft tissue sarcoma. Participants should be suitable for radiation therapy and surgery to remove the tumor. Specific eligibility criteria are not provided, but typically include factors like overall health status, age range, and having no other medical conditions that could interfere with the treatment or skew results.

Inclusion Criteria

I am very active or can carry out light work.

I am planning to have radiation therapy and surgery to try to cure my cancer.

I am medically cleared for surgery.

Exclusion Criteria

I have an active hepatitis B or C infection.

I have had pneumonitis that needed steroids or currently have it.

I do not have any conditions that the study excludes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

P-SFRT Treatment

Participants undergo proton-spatially fractionated radiotherapy (P-SFRT) over 1 fraction

1 day

1 visit (in-person)

IG-IMRT Treatment

Participants undergo image-guided intensity modulated radiation therapy (IG-IMRT) over 25-28 fractions

5-6 weeks

25-28 visits (in-person)

Surgical Intervention

Participants undergo surgical resection 21 to 35 days after radiation therapy

3-5 weeks post-radiation

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Follow-up visits at 30 and 90 days post-surgery, then up to 36 months

Treatment Details

Interventions

• Proton-Spatially Fractionated Radiotherapy
• Standard Radiation Therapy

Trial Overview The study is testing a combination of proton-spatially fractionated radiotherapy (P-SFRT) alongside standard radiation therapy. P-SFRT aims to deliver high doses of radiation directly to the tumor while sparing surrounding healthy tissues. The goal is to determine the best dose and assess how well this approach works compared to traditional methods.

Participant Groups

Group I: Treatment (P-SFRT, IG-IMRT) Experimental Treatment 6 Interventions

Patients undergo P-SFRT over 1 fraction and then undergo IG-IMRT over 25-28 fractions for 35 to 42 days. Patients undergo surgical resection 21 to 35 days after radiation therapy. Patients undergo blood sample collection during screening and on study. Patients also undergo biopsy during screening and CT on study and on follow up.

Proton-Spatially Fractionated Radiotherapy is already approved in United States, European Union for the following indications:

Approved in United States as Spatially Fractionated Radiation Therapy for:

• Soft tissue sarcoma
• Non-small cell lung cancer

Approved in European Union as Spatially Fractionated Radiation Therapy for:

• Soft tissue sarcoma
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Proton spatially fractionated GRID radiation (SFGRT) was successfully used to treat 10 patients with large tumors that could not be treated with photon GRID due to critical organ proximity, showing an 80% rate of tumor regression or local symptom improvement.

The treatment was well-tolerated, with 50% of patients experiencing only mild acute side effects, indicating that proton SFGRT is a feasible and effective alternative for patients who cannot receive photon-based treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early clinical results of proton spatially fractionated GRID radiation therapy (SFGRT). Mohiuddin, M., Lynch, C., Gao, M., et al.[2022]

Proton therapy for neoadjuvant treatment of soft tissue sarcoma (STS) in 11 adult patients demonstrated significant dosimetric advantages over conventional photon therapy, including lower mean doses to critical organs like the femur and femoral head, while maintaining effective target coverage.

The study found that proton therapy not only achieved the necessary coverage for the clinical target volume but also significantly reduced the integral dose and improved conformity and heterogeneity indices, suggesting a safer treatment option for patients with STS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing Ultra-hypofractionated Proton versus Photon Therapy in Extremity Soft Tissue Sarcoma. Thomas, R., Chen, H., Gogineni, E., et al.[2023]

The combination of photon irradiation followed by neutron boost irradiation in 23 patients with high-grade non-metastatic soft tissue sarcoma resulted in a remarkable 36-month local control rate of 91%, indicating effective management of local relapse risk.

The treatment also showed promising outcomes with a 36-month disease-free survival rate of 78% and overall survival rate of 87%, while complications were minimal and comparable to other treatments not using neutrons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A unique radiation scheme for the treatment of high-grade non-metastatic soft tissue sarcoma: the detroit medical center experience. Fontanesi, J., Mott, MP., Kraut, MJ., et al.[2021]

A patient with high-grade soft tissue sarcoma showed an excellent pathologic response to neoadjuvant proton therapy, suggesting that this treatment may enhance tumor response compared to traditional methods.

Proton therapy's ability to deliver highly conformal doses while sparing surrounding healthy tissues could be beneficial in treating radio-insensitive tumors like soft tissue sarcomas, although further research is needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Excellent Pathologic Response and Atypical Clinical Course of High-Grade Extremity Sarcoma to Neoadjuvant Pencil Beam Scanning Proton Therapy. Remick, J., Regine, W., Malyapa, R., et al.[2020]

Proton beam therapy offers a significant dosimetric advantage over traditional x-ray radiation therapy by reducing radiation exposure to healthy tissues, which could enhance treatment outcomes for sarcomas.

This therapy may improve the therapeutic ratio by either increasing the dose to the tumor for better local control or decreasing complications in surrounding normal tissues, making it a promising option for sarcoma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton therapy for sarcomas. Keole, S., Ashman, JB., Daniels, TB.[2014]

Spot scanning proton beam therapy (PT) demonstrated effective treatment for soft-tissue sarcoma (STS) in 13 adult patients, with a 4-year local control rate of 74.1% and metastasis-free survival rate of 84.6%.

The treatment was found to be safe, with only 2 patients experiencing late grade >2 toxicity, indicating an acceptable safety profile for patients with tumors near critical structures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spot scanning proton therapy in the curative treatment of adult patients with sarcoma: the Paul Scherrer institute experience. Weber, DC., Rutz, HP., Bolsi, A., et al.[2018]

Proton therapy is preferred for treating pediatric sarcomas because it effectively spares healthy tissue, reducing potential damage compared to traditional photon therapies.

This treatment has a proven track record in managing specific types of tumors, like chondrosarcomas and chordomas, and ongoing clinical trials are evaluating its effectiveness in various sarcoma cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Proton therapy in soft tissue and bone sarcomas]. Thariat, J., Tessonnier, T., Bonvalot, S., et al.[2018]

In a study of 62 patients with skull base sarcomas treated with carbon-ion and proton radiation therapy, the 1-year overall survival rate was 91.2%, indicating effective tumor control and promising outcomes for this treatment approach.

The therapy was associated with minimal toxicities, with only one patient experiencing severe complications, suggesting that particle beam radiation therapy is a safe option for patients with skull base sarcomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Particle Beam Radiation Therapy for Skull Base Sarcomas. Yang, J., Hu, W., Guan, X., et al.[2020]

Proton beam radiotherapy offers significant advantages over standard photon radiation for treating pediatric sarcomas by minimizing radiation exposure to surrounding healthy tissues, which is crucial given the proximity of these tumors to critical structures and growing organs.

Emerging data suggests that proton therapy not only improves dosimetric outcomes compared to traditional radiation methods like IMRT and 3D conformal radiation but also shows promising long-term clinical outcomes and reduced toxicity in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton radiotherapy for pediatric sarcoma. Ladra, MM., Yock, TI.[2021]

Proton therapy can be a safer alternative for reirradiation and irradiation of sarcomas, as it helps reduce the risk of toxicity associated with high doses of radiation.

The review highlights the potential of proton therapy to improve tumor control while minimizing damage to surrounding healthy tissues, making it a valuable option in challenging cases of sarcoma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of proton therapy in reirradiation and in the treatment of sarcomas. Doyen, J., Aloi, D., Groulier, A., et al.[2021]

References

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

Early clinical results of proton spatially fractionated GRID radiation therapy (SFGRT). [2022]

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

Comparing Ultra-hypofractionated Proton versus Photon Therapy in Extremity Soft Tissue Sarcoma. [2023]

3. Egypt pubmed.ncbi.nlm.nih.gov

A unique radiation scheme for the treatment of high-grade non-metastatic soft tissue sarcoma: the detroit medical center experience. [2021]

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

Excellent Pathologic Response and Atypical Clinical Course of High-Grade Extremity Sarcoma to Neoadjuvant Pencil Beam Scanning Proton Therapy. [2020]

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

Proton therapy for sarcomas. [2014]

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

Spot scanning proton therapy in the curative treatment of adult patients with sarcoma: the Paul Scherrer institute experience. [2018]

7. France pubmed.ncbi.nlm.nih.gov

[Proton therapy in soft tissue and bone sarcomas]. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Particle Beam Radiation Therapy for Skull Base Sarcomas. [2020]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Proton radiotherapy for pediatric sarcoma. [2021]

10. France pubmed.ncbi.nlm.nih.gov

Role of proton therapy in reirradiation and in the treatment of sarcomas. [2021]