Proton Radiation for Uterine Cancer

(PROPS GYN Trial)

Recruiting at 4 trial locations

Overseen By Project Manager

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Abramson Cancer Center of the University of Pennsylvania

Disqualifiers: Prior pelvic radiation, Metastatic disease, Inflammatory bowel disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new radiation treatment, Whole Pelvis Pencil Beam Scanning Proton Radiation, to determine if it causes fewer stomach and gut issues when treating gynecologic cancers, such as cervical or endometrial cancer, after surgery. The goal is to assess the safety and effectiveness of this treatment in reducing side effects compared to traditional methods. Individuals who recently underwent surgery for cervical or endometrial cancer and require radiation therapy might be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

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

What prior data suggests that Whole Pelvis Pencil Beam Scanning Proton Radiation is safe for treating gynecologic cancers?

Research has shown that Whole Pelvis Pencil Beam Scanning Proton Radiation (WP PBS PRT) is generally safe for treating gynecologic cancers. In earlier studies, patients experienced few digestive or urinary issues after treatment, indicating low rates of gastrointestinal (GI) and genitourinary (GU) problems. This suggests the treatment is usually well-tolerated. Current evidence supports its safety, making it a promising option for those considering this type of radiation therapy. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for uterine cancer?

Researchers are excited about Whole Pelvis (WP) Pencil Beam Scanning Proton Radiation (PBS PRT) for uterine cancer because it offers a novel approach to radiation therapy. Unlike traditional radiation treatments that often affect surrounding healthy tissues, PBS PRT uses a highly precise proton beam that targets cancer cells more accurately, potentially reducing side effects. This precision allows for higher doses of radiation to be delivered directly to the tumor site, which could lead to better outcomes in the post-hysterectomy setting. Additionally, this method aligns with guidelines for treating the entire pelvic area, making it a comprehensive option for patients.

What evidence suggests that Whole Pelvis Pencil Beam Scanning Proton Radiation is effective for uterine cancer?

Research has shown that Whole Pelvis Pencil Beam Scanning Proton Radiation (PBS PRT), which participants in this trial will receive, holds promise for treating gynecologic cancers, such as uterine cancer, after surgery. This proton therapy precisely targets cancer cells while protecting healthy tissues, reducing side effects. Early findings suggest that patients experience fewer stomach and digestive issues during treatment. Long-term studies have also demonstrated good results in controlling cancer growth and maintaining patient safety. Overall, evidence supports PBS PRT as an effective treatment for gynecologic cancers with fewer unwanted side effects. ^{1 2 4 6 7}

Who Is on the Research Team?

Neil K Taunk, MD, MSCTS

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for adults over 18 with confirmed cervical or endometrial cancer who need additional radiation therapy after surgery. Participants should be able to perform daily activities with minimal assistance (ECOG 0-2) and must provide written consent.

Inclusion Criteria

My cancer is confirmed to be either cervical or endometrial.

I am recommended to have radiation therapy for my pelvic area, with or without additional treatments.

You have given permission in writing to take part in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive Whole Pelvis Pencil Beam Scanning Proton Radiation (PBS PRT) as part of the definitive treatment of gynecologic cancers in the post-hysterectomy, adjuvant setting. Patients will be treated with doses of 45 or 50.4 Gy in 1.8 Gy daily fractions.

5-6 weeks

Follow-up

Participants are monitored for acute clinician-reported gastrointestinal (GI) and genitourinary (GU) toxicity, quality of life, and survival outcomes.

Up to 6 months

Long-term follow-up

Participants are monitored for loco-regional recurrence free survival, disease free survival, and overall survival.

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Whole Pelvis (WP) Pencil Beam Scanning Proton Radiation (PBS PRT)

Trial Overview The study is testing a type of targeted radiation called Whole Pelvis Pencil Beam Scanning Proton Radiation in patients who have had surgery for gynecologic cancers, aiming to reduce gastrointestinal side effects.

How Is the Trial Designed?

Group I: Adjuvant Whole Pelvis (WP) Pencil Beam Scanning Proton Radiation (PBS PRT) Experimental Treatment 1 Intervention

The study intervention is Whole Pelvis (WP) Pencil Beam Scanning Proton Radiation (PBS PRT) as part of the definitive treatment of gynecologic cancers in the post-hysterectomy, adjuvant setting. Patients will be treated with doses of 45 or 50.4 Gy in 1.8 Gy daily fractions. The volume treated will include the whole pelvis according to Radiation Therapy Oncology Group post-hysterectomy pelvis guidelines.

Whole Pelvis (WP) Pencil Beam Scanning Proton Radiation (PBS PRT) is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Proton Therapy for:

• Gynecologic cancers including cervical, ovarian, uterine, vaginal, and vulvar cancers

Approved in European Union as Proton Therapy for:

• Gynecologic cancers including cervical, ovarian, uterine, vaginal, and vulvar cancers

Approved in Canada as Proton Therapy for:

• Gynecologic cancers including cervical, ovarian, uterine, vaginal, and vulvar cancers

Approved in Japan as Proton Therapy for:

• Gynecologic cancers including cervical, ovarian, uterine, vaginal, and vulvar cancers

Who Is Running the Clinical Trial?

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Published Research Related to This Trial

Proton Pencil Beam Scanning (PBS) can potentially deliver high FLASH dose rates (≥40 Gy/s) effectively, but this is limited to smaller fields (less than 4x4 cm²) and requires cyclotron output currents above 500 nA.

While achieving FLASH dose rates for larger fields is challenging, local FLASH delivery to specific areas of the treatment volume is feasible, suggesting that with further research, PBS techniques can be adapted for enhanced FLASH proton radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current delivery limitations of proton PBS for FLASH. Zou, W., Diffenderfer, ES., Cengel, KA., et al.[2021]

In a study of 304 men with localized prostate cancer, those treated with pencil beam scanning (PBS) showed a higher proportion of significant declines in urinary quality of life (QOL) compared to those treated with passive scatter/uniform scanning (PS/US) at 12 months, indicating a potential difference in outcomes between the two proton therapy methods.

However, overall average quality-of-life declines did not significantly differ between PBS and PS/US, suggesting that while there may be specific areas of concern, both treatment modalities have similar average effects on patient-reported outcomes over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient reported outcomes following proton pencil beam scanning vs. passive scatter/uniform scanning for localized prostate cancer: Secondary analysis of PCG 001-09. Mishra, MV., Khairnar, R., Bentzen, SM., et al.[2022]

In a study of 19 children with neuroblastoma treated with pencil beam scanning proton beam therapy (PBS-PT), the early outcomes were promising, showing a 2-year overall survival rate of 94% and no local recurrences during a median follow-up of 14.9 months.

The use of volumetric rescanning (vRSC) for motion mitigation was found to be safe and feasible, although its clinical relevance may be limited for children with minimal organ motion (<5 mm) during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pencil Beam Scanning Proton Therapy for Paediatric Neuroblastoma with Motion Mitigation Strategy for Moving Target Volumes. Lim, PS., Pica, A., Hrbacek, J., et al.[2022]

A novel patient-specific quality assurance (psQA) program using a high-resolution 2D strip ionization chamber array (SICA) was developed and validated for ultra-high dose rate (UHDR) FLASH proton therapy, demonstrating excellent accuracy in measuring dose and dose rate.

The SICA-based QA framework achieved high gamma passing rates (96.6% for dose and 98.8% for dose rate) compared to treatment planning system predictions, indicating its effectiveness in ensuring the safety and efficacy of FLASH radiotherapy in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementation of novel measurement-based patient-specific QA for pencil beam scanning proton FLASH radiotherapy. Huang, S., Yang, Y., Wei, S., et al.[2023]

In a study of 11 women with gynecologic cancers receiving pencil beam scanning (PBS) proton therapy, the treatment showed a low incidence of acute toxicities, with only 33% experiencing grade 2 hematologic toxicities and 9% experiencing grade 3 gastrointestinal toxicity, indicating a relatively safe profile.

PBS demonstrated significant dosimetric advantages over intensity-modulated radiation therapy (IMRT), particularly in sparing surrounding normal tissues like pelvic bone marrow, bladder, and small bowel from low doses, while maintaining robust target coverage despite setup uncertainties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Report of Pencil Beam Scanning Proton Therapy for Posthysterectomy Patients With Gynecologic Cancer. Lin, LL., Kirk, M., Scholey, J., et al.[2020]

In a study involving 11 patients with rectal cancer, preoperative short-course pencil beam scanning proton therapy (PBS-PT) effectively reduced radiation exposure to normal tissues compared to traditional photon therapies (3DCRT and VMAT).

PBS-PT provided similar coverage of the clinical target volume while significantly lowering the radiation dose to critical organs like the small and large bowel, bladder, and femoral heads, suggesting a safer treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Implementation of Preoperative Short-Course Pencil Beam Scanning Proton Therapy for Patients With Rectal Cancer. Jeans, EB., Jethwa, KR., Harmsen, WS., et al.[2022]

Proton pencil beam scanning (PBS) therapy significantly reduces the risk of secondary cancers in breast cancer patients compared to traditional photon therapies, with a notable reduction in risk for younger patients with nodal involvement.

In a study involving 10 breast cancer patients, PBS showed a lower cumulative excess absolute risk for secondary cancers in the lungs and contralateral breast compared to tangential 3D-CRT and VMAT, highlighting its potential as a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton pencil beam scanning reduces secondary cancer risk in breast cancer patients with internal mammary chain involvement compared to photon radiotherapy. Cartechini, G., Fracchiolla, F., Menegotti, L., et al.[2021]

Pencil Beam Scanning Proton Therapy (PBS-PT) provides equivalent target coverage for cervical cancer patients compared to traditional photon Volumetric Modulated Arc Therapy (VMAT), while also significantly reducing radiation exposure to surrounding organs at risk (OARs).

In this study involving 12 cervical cancer patients, PBS-PT demonstrated lower doses to critical areas such as the bowel and bone marrow, indicating a potential for reduced toxicity and improved safety in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inter-fraction motion robustness and organ sparing potential of proton therapy for cervical cancer. Gort, EM., Beukema, JC., Matysiak, W., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26372435/

Initial Report of Pencil Beam Scanning Proton Therapy for ... Our results have demonstrated the clinical feasibility of PBS and the dosimetric advantages, especially for the low-dose sparing of normal tissues in the ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05758688

Study Details | NCT05758688 | PROton Therapy for Post ... The study intervention is Whole Pelvis (WP) Pencil Beam Scanning Proton Radiation (PBS PRT) as part of the definitive treatment of gynecologic cancers in the ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S036030162500238X

Long-Term Results of a Phase 2 Study of Adjuvant Proton ... Patients received 45 Gy(relative biological effectiveness) in 25 fractions with pencil beam scanning proton therapy (PBS-PT). Primary endpoints included ...

4. redjournal.org redjournal.org/article/S0360-3016(24)00970-2/fulltext

Five-Year Outcomes of a Phase II Study of Post-Operative ... A prospective phase II study was conducted to evaluate the safety and efficacy of proton beam RT for patients with LN+ uterine or cervical ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37003073/

Acute and long-term toxicity of whole pelvis proton ... Methods: We reviewed 23 patients treated from 2013 to 2019 with WP PBS PRT for endometrial, cervical, and vaginal cancer. We report acute and ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0360301623000123

Treatment Tolerability and Toxicity of Postoperative Proton ... The APROVE study is a prospective one-arm phase-2 study investigating the safety and treatment tolerability of postoperative proton beam therapy in women

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-09737

Whole Pelvis Proton Radiation Therapy for the Treatment ... This phase II trial tests how well whole pelvis (WP) proton radiation therapy works in treating patients with cervical or endometrial cancer after surgery.