Proton Radiotherapy for Solid Tumors

(PARTy Trial)

Overseen By Allen Mo, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Disqualifiers: Small cell carcinoma, Uncontrolled illness, Pregnant, 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

Duration: 2 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a pilot study evaluating the feasibility of daily online adaptive planning for patients undergoing proton radiation therapy. Patients undergoing proton radiation therapy normally undergo extensive pre-planning for their treatment. However, accounting for uncertainties in treatment delivery remains a challenge for a variety of reasons, such as differences in patient anatomy from pre-planning to the day of treatment. Online adaptive planning is a process consisting of generating the original pre-plan on the patient on a treatment day, assessing the pre-plan's coverage and safety, and if changes are needed, the plan is changed in order to optimize the treatment while the patient is still on the treatment table. This study is assessing the feasibility and safety of this approach in order to gather data for a larger trial.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the treatment Proton SBRT for solid tumors?

Research shows that Proton SBRT can effectively target and treat early-stage lung cancer with potentially fewer side effects compared to traditional radiation methods. Additionally, Proton SBRT has been used successfully for liver metastases, indicating its potential effectiveness for other solid tumors. ^{1 2 3 4 5}

Is proton radiotherapy generally safe for humans?

Research shows that proton-based stereotactic body radiation therapy (SBRT) is being studied for its safety and ability to reduce damage to normal tissues compared to traditional radiation methods. Studies on lung and liver cancers suggest that proton therapy may have fewer severe side effects than photon-based treatments. ^{2 5 6 7 8}

How is Proton SBRT different from other treatments for solid tumors?

Proton SBRT is unique because it uses protons instead of traditional photons to deliver radiation, which allows for more precise targeting of tumors and reduces damage to surrounding healthy tissues. This can be particularly beneficial for high-risk tumors where traditional radiation struggles to deliver effective doses without harming nearby organs. ^{1 2 3 5 9}

Research Team

Allen Mo, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This clinical trial is open to individuals with solid tumors who are scheduled for proton radiation therapy. The study aims to test a new method of planning treatment on the same day as delivery, adjusting for any changes in patient anatomy.

Inclusion Criteria

Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, or a male suspect he has fathered a child, s/he must inform the treating physician immediately.

I have had radiation therapy before.

I am mostly able to care for myself and carry out normal activities.

Exclusion Criteria

Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days of study entry.

I cannot undergo proton therapy due to medical reasons or my doctor thinks I'm not fit for SBRT.

I have another cancer, but it won't affect this trial's treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive proton stereotactic body radiotherapy (SBRT) with daily online adaptive planning for a total of 5 fractions

2 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on radiation-related toxicities

3 months

Treatment Details

Interventions

• Proton SBRT

Trial Overview The trial is testing online adaptive planning in proton SBRT (a type of targeted radiation therapy). It involves creating and possibly modifying a treatment plan directly before administering it, to ensure precision and safety.

Participant Groups

Group I: Proton Stereotactic Body Radiotherapy (SBRT) Experimental Treatment 1 Intervention

All patients will receive standard of care proton SBRT either daily or every other day for a total of 5 fractions. At the time of each treatment, the initial pre-plan will be generated on the patient and assessed for coverage and safety. An adaptive plan based on the patient's anatomy that day will also be generated and then compared to the initial pre-plan. The optimal treatment plan will be chosen and administered to the patient on that day. This process will be repeated for each fraction for every patient.

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

Approved in United States as Proton Radiation Therapy for:

• Various cancers including but not limited to brain, spine, lung, liver, pancreas, prostate, breast, and pediatric cancers

Approved in European Union as Proton Radiation Therapy for:

• Various cancers including but not limited to ocular melanoma, chordomas, chondrosarcomas, and pediatric cancers

Approved in Japan as Proton Radiation Therapy for:

• Various cancers including but not limited to prostate, lung, liver, and pediatric cancers

Approved in Canada as Proton Radiation Therapy for:

• Various cancers including but not limited to brain, spine, and pediatric cancers

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

The Foundation for Barnes-Jewish Hospital

Collaborator

Trials

43

Recruited

6,600+

Findings from Research

Proton stereotactic body radiation therapy (SBRT) demonstrated a high local control rate of 92.5% for liver metastases in a study of 46 patients, with a median follow-up of 15 months.

The treatment was well-tolerated, with low toxicity rates (37% grade 1 and 6.5% grade 2), and no severe toxicities or cases of radiation-induced liver disease, indicating a safe profile for managing multiple liver lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton stereotactic body radiation therapy for liver metastases-results of 5-year experience for 81 hepatic lesions. Coffman, AR., Sufficool, DC., Kang, JI., et al.[2022]

The study aimed to compare the efficacy and toxicity of stereotactic body radiation therapy (SBRT) and stereotactic body proton therapy (SBPT) in treating high-risk, medically inoperable early-stage non-small cell lung cancer, but it closed early due to low patient enrollment, with only 21 patients participating.

At a median follow-up of 32 months, the SBPT group showed promising results with a 90% three-year overall survival rate and 90% local control, while the SBRT group had a 27.8% three-year overall survival rate, indicating potential advantages of SBPT despite the study's limitations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 Study of Stereotactic Body Radiation Therapy and Stereotactic Body Proton Therapy for High-Risk, Medically Inoperable, Early-Stage Non-Small Cell Lung Cancer. Nantavithya, C., Gomez, DR., Wei, X., et al.[2022]

Proton therapy (PT) and stereotactic body radiotherapy (SBRT) showed similar effectiveness in delivering doses to the planning target volume (PTV) for early-stage non-small-cell lung cancer, but PT generally resulted in lower doses to normal tissues, particularly the lungs.

Actively scanned proton therapy provided better dose characteristics compared to passively scattered plans, indicating a potential advantage in minimizing damage to surrounding healthy tissues, although the clinical significance of these differences needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton beam radiotherapy versus three-dimensional conformal stereotactic body radiotherapy in primary peripheral, early-stage non-small-cell lung carcinoma: a comparative dosimetric analysis. Macdonald, OK., Kruse, JJ., Miller, JM., et al.[2022]

In a study involving 12 patients, proton therapy (both passively scattered and intensity-modulated) showed similar target conformity to conventional photon therapy (3D-CRT) for hypofractionated stereotactic body radiotherapy, indicating comparable effectiveness in targeting lung lesions.

Proton therapy techniques significantly reduced radiation exposure to the heart and contralateral lung, achieving almost 0Gy to the heart compared to around 3Gy with photon therapy, suggesting potential safety benefits, although the clinical impact of these dosimetric advantages needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can protons improve SBRT for lung lesions? Dosimetric considerations. Georg, D., Hillbrand, M., Stock, M., et al.[2018]

In a study involving 8 patients with early-stage non-small-cell lung cancer, proton-based stereotactic body radiotherapy (pSBRT) demonstrated significant dosimetric improvements over photon-based SBRT (xSBRT), reducing radiation exposure to normal lung tissue and critical organs like the heart and esophagus.

pSBRT resulted in lower doses to normal structures, with significant reductions in lung exposure at various dose levels (e.g., V5 and V10), suggesting a potential for reduced toxicity compared to xSBRT, although the clinical significance of these findings is still uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-scattered proton-based stereotactic body radiotherapy for stage I lung cancer: a dosimetric comparison with photon-based stereotactic body radiotherapy. Hoppe, BS., Huh, S., Flampouri, S., et al.[2018]

Proton-based stereotactic body radiation therapy (SBRT) for liver metastases showed a one-year local control rate of 71.9% and was well tolerated, with no severe toxicities reported in a study of 89 patients over a median follow-up of 30.1 months.

KRAS mutations were identified as a significant predictor of poor local control, highlighting the importance of genetic testing before treatment to tailor approaches for patients with liver metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Proton-Based Stereotactic Body Radiation Therapy for Liver Metastases: Importance of Tumor Genotype. Hong, TS., Wo, JY., Borger, DR., et al.[2022]

Stereotactic body proton therapy (SBPT) showed greater dose escalation potential compared to stereotactic body photon therapy (SBXT) in treating prostate cancer, particularly for larger prostate volumes, indicating it may be a more effective option for high-risk patients.

In a study of 25 patients, SBPT resulted in lower doses to critical structures like the bladder neck while still achieving significant target coverage, suggesting a safer treatment profile with potentially fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simulation of an HDR "Boost" with Stereotactic Proton versus Photon Therapy in Prostate Cancer: A Dosimetric Feasibility Study. Remick, JS., Sabouri, P., Zhu, M., et al.[2022]

In a study involving 15 patients with centrally or superiorly located stage I non-small-cell lung cancer (NSCLC), intensity-modulated proton therapy (IMPT) and passive-scattering proton therapy (PSPT) were found to significantly reduce radiation exposure to surrounding healthy tissues compared to conventional photon stereotactic body radiation therapy (SBRT).

IMPT and PSPT plans not only improved tumor coverage but also minimized the maximum tolerated dose to critical structures like the heart and spinal cord, demonstrating their potential for safer treatment options in patients with challenging tumor locations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton stereotactic body radiation therapy for clinically challenging cases of centrally and superiorly located stage I non-small-cell lung cancer. Register, SP., Zhang, X., Mohan, R., et al.[2021]

Stereotactic body proton therapy (SBPT) demonstrated effective local control rates for high-risk lung tumors, achieving 89% local control for early-stage non-small cell lung cancer (NSCLC) and 100% for locally recurrent NSCLC over three years, while maintaining excellent tumor coverage without compromising safety.

The treatment exhibited a favorable toxicity profile, with only 7.4% of patients experiencing significant pulmonary toxicity, and no severe toxicities related to other organs, suggesting SBPT is a promising option for patients with challenging lung tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of stereotactic body proton therapy for high-risk lung tumors. McMillan, MT., Shepherd, AF., Kang, M., et al.[2023]

References

1. China pubmed.ncbi.nlm.nih.gov

Proton stereotactic body radiation therapy for liver metastases-results of 5-year experience for 81 hepatic lesions. [2022]

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

Phase 2 Study of Stereotactic Body Radiation Therapy and Stereotactic Body Proton Therapy for High-Risk, Medically Inoperable, Early-Stage Non-Small Cell Lung Cancer. [2022]

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

Proton beam radiotherapy versus three-dimensional conformal stereotactic body radiotherapy in primary peripheral, early-stage non-small-cell lung carcinoma: a comparative dosimetric analysis. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

Can protons improve SBRT for lung lesions? Dosimetric considerations. [2018]

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

Double-scattered proton-based stereotactic body radiotherapy for stage I lung cancer: a dosimetric comparison with photon-based stereotactic body radiotherapy. [2018]

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

Phase II Study of Proton-Based Stereotactic Body Radiation Therapy for Liver Metastases: Importance of Tumor Genotype. [2022]

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

Simulation of an HDR "Boost" with Stereotactic Proton versus Photon Therapy in Prostate Cancer: A Dosimetric Feasibility Study. [2022]

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

Proton stereotactic body radiation therapy for clinically challenging cases of centrally and superiorly located stage I non-small-cell lung cancer. [2021]

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

Safety and efficacy of stereotactic body proton therapy for high-risk lung tumors. [2023]