Proton Therapy for Sarcoma

(PRONTO Trial)

Recruiting at 1 trial location

Overseen By Curtiland Deville

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Chemotherapy, Targeted agents, Immunotherapy

Disqualifiers: Prior radiation, Retroperitoneal tumor, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests proton therapy, a type of radiation therapy, to determine its safety and effectiveness for certain types of sarcoma, a cancer that can occur in the body's soft tissues. Participants will receive five sessions of this therapy before surgery. Researchers will monitor for complications with wound healing and assess the treatment's impact on daily life and overall well-being. Suitable candidates have primary or locally recurring sarcoma in their limbs or body (excluding the abdomen) and have not undergone previous radiation treatments in the same area. As an unphased trial, this study provides a unique opportunity to contribute to pioneering research in proton therapy for 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, if you are planned for systemic therapy like chemotherapy, you may not be eligible to participate.

What prior data suggests that proton therapy is safe for treating sarcoma?

Research has shown that hypofractionated proton therapy is generally safe for treating various types of cancer. Studies have found this radiation treatment safe for patients with central lung cancer, providing good results with manageable side effects. Another study found it safe and effective for patients with early-stage prostate cancer.

For soft tissue sarcomas, hypofractionated radiotherapy has proven to be as safe and effective as standard treatments, indicating that the treatment is well-tolerated with mild side effects.

Overall, existing research supports the safety of hypofractionated proton therapy in humans, with evidence from other conditions suggesting it is a reliable option with generally mild side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Hypofractionated proton therapy is unique for treating sarcoma because it delivers a high dose of radiation in fewer sessions compared to traditional methods. Traditional treatments like conventional radiation therapy typically require daily sessions over several weeks, but this approach condenses treatment into just five sessions. This not only potentially reduces the overall treatment time but also minimizes exposure to surrounding healthy tissues, which could lead to fewer side effects. Researchers are excited about this method because it aims to improve patient convenience and outcomes by combining effective tumor targeting with a more patient-friendly schedule.

What evidence suggests that hypofractionated proton therapy is effective for sarcoma?

Research shows that hypofractionated proton therapy effectively treats sarcoma. Studies have found that this therapy reduces radiation exposure to nearby organs compared to traditional radiation treatments, potentially causing fewer side effects. Early results suggest that using proton therapy before surgery benefits the management of soft tissue sarcomas. In this trial, participants will receive pre-operative hypofractionated proton therapy. Patients in earlier trials experienced good outcomes, supporting its potential effectiveness. ^{2 4 6 7 8}

Who Is on the Research Team?

Curtland Deville, MD

Principal Investigator

Johns Hopkins School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults (18+) with primary or locally recurrent sarcoma in the limbs or trunk. Participants should be able to perform daily activities with minimal assistance (WHO/ECOG status ≤2).

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

My cancer is in the limbs or torso and hasn't spread far.

Exclusion Criteria

Confirmed pregnancy

Inability to tolerate treatment position for duration of simulation or treatment

My cancer started in the back of my abdomen.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative Hypofractionated Proton Therapy

Participants receive five fractions of proton therapy before surgical resection of their sarcoma

1-2 weeks

Surgery

Participants undergo surgical resection of their sarcoma

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including wound complications and quality of life assessments

2 years

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Hypofractionated Proton Therapy

Trial Overview The study tests if a short course of proton therapy, given in five sessions before surgery, is safe and effective for soft tissue sarcomas of the extremity and trunk. It will assess wound healing and life quality post-treatment.

How Is the Trial Designed?

Group I: Pre-operative hypofractionated proton therapy Experimental Treatment 1 Intervention

Patients will have 5 fractions of proton therapy prior to surgical resection of their sarcoma.

Hypofractionated Proton Therapy is already approved in United States, European Union, Japan for the following indications:

Approved in United States as Proton Therapy for:

• Prostate cancer
• Brain tumors
• Spinal cord tumors
• Head and neck cancers
• Retroperitoneal sarcomas

Approved in European Union as Proton Therapy for:

• Prostate cancer
• Brain tumors
• Spinal cord tumors
• Head and neck cancers
• Eye tumors

Approved in Japan as Proton Therapy for:

• Prostate cancer
• Brain tumors
• Spinal cord tumors
• Head and neck cancers
• Pediatric cancers

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Robert L. Sloan Fund for Cancer Research

Collaborator

Trials

5

Recruited

70+

Robert L. Sloan Fund for Cancer Research

Collaborator

Trials

5

Recruited

70+

Published Research Related to This Trial

In a study of 17 patients with extremity soft sarcoma, proton beam therapy (PBT) showed a significant advantage in sparing surrounding soft tissue and bone compared to intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT).

The mean dose to soft tissue was significantly lower with PBT (2 Gy) compared to IMRT (11 Gy) and 3D-CRT (13 Gy), and the mean dose to adjacent bone was also lower with PBT (15 Gy) compared to IMRT (26 Gy) and 3D-CRT (28 Gy), suggesting potential for reduced toxicity and improved patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric comparison between proton beam therapy, intensity modulated radiation therapy, and 3D conformal therapy for soft tissue extremity sarcoma. Laughlin, BS., Golafshar, M., Prince, M., et al.[2023]

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]

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]

Hypofractionated proton beam therapy (hPBT) demonstrated a more favorable toxicity profile compared to normofractionated proton beam therapy (nPBT), particularly in patients treated for abdominal and pelvic cancers, with fewer severe toxicity events and better recovery rates.

Quality of life outcomes were similar between hPBT and nPBT, with some specific improvements noted in role functioning and pain management for hPBT, suggesting that hPBT is a safe and effective alternative that merits further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Normofractionated and moderately hypofractionated proton therapy: comparison of acute toxicity and early quality of life outcomes. Pelak, MJ., Flechl, B., Hug, E., et al.[2022]

In a study of 20 patients with central lung cancer treated with high total dose hypofractionated proton beam therapy, there were no severe toxicities (Grade 3 or higher), indicating a strong safety profile for this treatment approach.

The therapy resulted in a 2-year overall survival rate of 73.8% and a local control rate of 78.5%, demonstrating its efficacy, especially in operable patients who had a 100% survival rate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High Dose Hypofractionated Proton Beam Therapy is a Safe and Feasible Treatment for Central Lung Cancer. Ono, T., Yabuuchi, T., Nakamura, T., et al.[2019]

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]

The phase 1 trial involving 18 patients with stage II or III non-small cell lung cancer demonstrated that hypofractionated proton therapy combined with chemotherapy has an acceptable safety profile, with no severe adverse events attributed to radiation therapy.

The study did not identify a maximum tolerated dose, and while two severe adverse events occurred, they were linked to chemotherapy rather than the proton therapy, suggesting that this treatment approach is safe for further investigation in phase 2 trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated Proton Therapy with Concurrent Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Phase 1 Trial from the University of Florida and Proton Collaborative Group. Hoppe, BS., Nichols, RC., Flampouri, S., et al.[2021]

In a study of 16 patients with soft tissue sarcoma, preoperative hypofractionated radiation therapy (30 Gy in 5 fractions) followed by immediate surgical resection resulted in no local failures and a median time of 20 days from biopsy to treatment completion.

Wound healing complications occurred in 31% of patients, with only 19% requiring additional surgery, indicating that this treatment approach has a favorable safety profile in terms of wound healing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Outcomes of Preoperative 5-Fraction Radiation Therapy for Soft Tissue Sarcoma Followed by Immediate Surgical Resection. Parsai, S., Lawrenz, J., Kilpatrick, S., et al.[2022]

Hypofractionated radiotherapy, used in 30 patients with non-metastatic soft tissue and bone sarcomas, demonstrated a 1-year overall survival rate of 75% and a 2-year local recurrence-free survival rate of 48%, indicating its efficacy in managing these cancers.

The treatment was generally safe, with only one case of severe late toxicity (grade 3 trismus), suggesting that hypofractionated radiotherapy can be a viable option for both primary treatment and reirradiation in sarcoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated radiotherapy for non-metastatic bone and soft tissue sarcomas. Yuce Sari, S., Cengiz, M., Dauletkazin, A., et al.[2019]

In a study of 18 geriatric patients with high-risk soft tissue sarcomas, hypofractionated radiotherapy (25 Gy in 5 fractions) was well tolerated, with 17 out of 18 patients completing the treatment as planned.

The treatment showed a manageable wound healing complication rate and no isolated local recurrences, suggesting that hypofractionated radiotherapy could be a feasible alternative for frail patients who cannot undergo standard therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated preoperative radiotherapy for high risk soft tissue sarcomas in a geriatric patient population. Potkrajcic, V., Traub, F., Hermes, B., et al.[2022]

In a study of 289 prostate cancer patients, hypofractionated proton beam therapy (PBT) showed no significant differences in acute adverse event rates or quality of life, as measured by the International Prostate Symptom Score (IPSS), compared to conventionally fractionated PBT.

The study evaluated patients treated with different doses (2.0, 2.5, and 3.0 Gy RBE per fraction) and found that factors like diabetes, age, and androgen deprivation therapy did not influence the IPSS outcomes, suggesting that hypofractionated PBT is a safe option without increased toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute toxicity and patient-reported symptom score after conventional versus moderately hypofractionated proton therapy for prostate cancer. Iizumi, T., Ishikawa, H., Sekino, Y., et al.[2022]

In a phase 1/2 trial involving 28 patients with locally advanced non-small cell lung cancer (NSCLC), hypofractionated proton therapy combined with chemotherapy resulted in impressive 1-year overall survival rates of 89%, significantly higher than the 62% benchmark from previous studies.

The treatment was well-tolerated, with no severe esophagitis and only 14% of patients experiencing significant radiation-related pulmonary toxicity, suggesting that proton therapy may offer a safer alternative for patients with advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoradiation with Hypofractionated Proton Therapy in Stage II-III Non-Small Cell Lung Cancer: A Proton Collaborative Group Phase 2 Trial. Hoppe, BS., Nichols, RC., Flampouri, S., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9875823/

Comparing Ultra-hypofractionated Proton versus Photon ... Proton therapy maintained target coverage while significantly reducing integral and mean doses to the proximal organs at risk compared with RT.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07169344

Hypofractionated, 3-week, Preoperative Proton or X-ray ... The purpose of the study is to investigate whether a personalized selection of patients with localized soft tissue sarcoma for preoperative ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38745333/

Prospective phase II trial of preoperative hypofractionated ... Hypofractionated, preoperative RT has been shown to provide acceptable outcomes in prospective trials. Proton beam therapy (PBT) provides ...

4. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/articles/10.1186/s13014-024-02447-0

Prospective phase II trial of preoperative hypofractionated ... ... Hypofractionated, preoperative RT has been shown to provide acceptable outcomes in prospective trials. Proton beam therapy (PBT) provides ...

5. trial.medpath.com trial.medpath.com/clinical-trial/3a5d9e83f2a6c6cb/nct07173972-prosarc-2-hypofractionated-proton-radiotherapy-inoperable-soft-tissue-sarcoma

Dose-escalated, Hypofractionated, Definitive Proton ... The main inclusion criterion is patients with inoperable soft tissue sarcoma. The primary endpoint is 2-year local progression-free survival ( ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9425455/

comparison of acute toxicity and early quality of life outcomes High dose hypofractionated proton beam therapy is a safe and feasible treatment for central lung cancer. Radiol Oncol (2017) 51:324–30. doi: 10.1515/raon ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2331518023001300

Hypofractionated Proton Therapy in Early Prostate Cancer Hypofractionated proton therapy of 60 Gy in 20 fractions was safe and effective for patients with low-risk prostate cancer.

8. mdpi.com mdpi.com/2072-6694/17/7/1170

Hypofractionated Radiotherapy for Soft Tissue Sarcomas Hypofractionated radiotherapy may offer similar local control and toxicity outcomes in the management of soft tissue sarcomas (STS) compared to standard ...