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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a new radiation therapy, proton-spatially fractionated radiotherapy (P-SFRT), in combination with standard radiation for treating retroperitoneal soft tissue sarcoma. The focus is on determining the optimal dose and understanding the side effects. Individuals recently diagnosed with this type of sarcoma and having a tumor at least 3 cm in diameter may qualify for the trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Proton-Spatially Fractionated Radiotherapy (P-SFRT) is safe, even when combined with standard radiation therapy. In earlier studies, patients underwent P-SFRT without serious side effects, and some large tumors responded well, shrinking significantly. Another study found that modern treatments like P-SFRT are safe for treating sarcomas that are difficult to operate on or have spread. These findings suggest that P-SFRT is generally well-tolerated and may benefit patients with challenging tumors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Proton-Spatially Fractionated Radiotherapy (P-SFRT) for sarcoma because it combines the precision of proton therapy with a unique delivery method that minimizes damage to healthy tissue. Unlike conventional radiation therapies, which often involve a uniform dose to the entire tumor area, P-SFRT uses spatial fractionation, delivering radiation in a more targeted way. This approach aims to enhance the effectiveness of treatment while reducing side effects, offering a promising alternative to standard radiation therapy options like conventional photon-based therapy. Additionally, the integration with Intensity-Modulated Radiation Therapy (IG-IMRT) provides a comprehensive treatment plan that could improve patient outcomes.

What evidence suggests that Proton-Spatially Fractionated Radiotherapy with standard radiation therapy might be an effective treatment for retroperitoneal soft tissue sarcoma?

This trial will evaluate the combination of proton-spatially fractionated radiotherapy (P-SFRT) and standard radiation therapy for treating sarcoma. Studies have shown that P-SFRT can improve outcomes for patients with large tumors compared to standard radiation. P-SFRT delivers higher doses of radiation directly to the tumor, effectively shrinking it while sparing nearby healthy tissue. Research indicates that this method is particularly beneficial for sarcomas, which develop in soft tissues like muscles and fat. In a study with patients who had bulky tumors, those treated with spatially fractionated radiation achieved better results than those with traditional treatments. This suggests that P-SFRT, combined with standard radiation therapy, might be a promising approach for treating retroperitoneal soft tissue sarcoma. ^{1 2 3 4 6}

Who Is on the Research Team?

Seth M. Pollack

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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 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]

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06327477

Proton-Spatially Fractionated Radiotherapy and Standard ... Giving P-SFRT with standard radiation therapy may work better in treating patients with newly diagnosed retroperitoneal soft tissue sarcoma. Detailed ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2452109425001447

A Phase 1 Proton Spatially Fractionated Radiation Therapy ... Single-fraction SFRT has demonstrated markedly improved outcomes in patients with bulky disease compared to conventional daily fractionated RT, significantly ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10943518/

Spatially Fractionated Radiation Therapy in Sarcomas We analyzed clinical and treatment outcomes in patients with bone and soft tissue sarcomas treated with modern SFRT techniques. Methods and ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7066961/

Early clinical results of proton spatially fractionated GRID ... Approximately 70 patients with large and bulky tumors refractory to prior treatments were treated with photon spatially fractionated GRID radiation (SFGRT).

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06980259

Spatially Fractionated Radiotherapy Versus Conventional ... This study is a multicenter, prospective, randomized controlled phase II clinical trial designed to evaluate the efficacy and safety of Spatially Fractionated ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12240221/

Effectiveness and Safety of Lattice Radiotherapy in ... Lattice radiotherapy (LRT) is a novel spatially fractionated radiotherapy technique specifically designed to treat large tumors more ...