Vaginal Brachytherapy for Endometrial Cancer

Recruiting at 2 trial locations

Overseen By Song Wood

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Timothy Showalter, MD

Must not be taking: Investigational agents

Disqualifiers: Advanced stage cancer, prior pelvic radiation, investigational agents, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

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

Compensation: Varies

Number of Visits: 6

258 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two types of radiation treatments to assess their impact on sexual health in women with early-stage endometrial cancer. Participants will receive high-dose radiation through vaginal brachytherapy, either in three larger doses or six smaller doses. Women who have undergone surgery for endometrial cancer and currently show no signs of disease may be suitable for this study. As a Phase 3 trial, it represents the final step before FDA approval, providing participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are taking investigational agents or have taken any within 30 days before the study, you may not be eligible to participate.

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

Research has shown that HDR vaginal brachytherapy is generally safe. Studies have found that this treatment is well-tolerated, with low rates of both immediate and delayed side effects in the vaginal area. For example, one study found that patients experienced very few harmful effects on the vagina. Another study demonstrated that the treatment effectively reduces cancer recurrence in the vaginal area with limited risk.

Other studies indicate that patients maintain a good quality of life after receiving HDR vaginal brachytherapy. Short-term side effects are usually mild and manageable, suggesting that most people can undergo the treatment without major problems. Therefore, existing research supports the safety of HDR vaginal brachytherapy for those considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using high-dose-rate (HDR) vaginal brachytherapy for endometrial cancer treatment because it offers a targeted approach that can minimize damage to surrounding healthy tissues. Unlike traditional external beam radiation therapy, which affects a broader area, HDR brachytherapy delivers radiation directly to the cancer site via the vagina, which may reduce side effects and treatment time. This trial explores two dosing regimens: one using three treatments of 7 Gy for a total of 21 Gy and another with six treatments of 4 Gy for a total of 24 Gy. The potential for more precise dosing and a shorter treatment span could lead to improved patient outcomes and a better quality of life during treatment.

What evidence suggests that this trial's treatments could be effective for endometrial cancer?

Studies have shown that high-dose-rate (HDR) vaginal brachytherapy effectively treats early-stage endometrial cancer, significantly reducing the risk of cancer recurrence in the vagina. Research involving over 132,000 patients found that using HDR brachytherapy after surgery can lower the risk of dying from the cancer by up to 22%. The treatment is generally well-tolerated, even in women with a narrower vaginal anatomy. In this trial, participants will receive HDR vaginal brachytherapy in different treatment arms, with some receiving 3 treatments of 7Gy and others receiving 6 treatments of 4Gy. Overall, HDR vaginal brachytherapy is widely recognized as an effective post-surgery treatment option for early-stage endometrial cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Kara Romano, MD

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

This trial is for adults over 18 with early-stage endometrial cancer (Stage I-II) who've had a hysterectomy and possibly lymph node removal. They should be able to follow the study plan, have no remaining measurable disease post-surgery, and an expected lifespan of at least one year. It's not for those with prior pelvic radiation, current investigational drug use, uncontrolled medical issues, or advanced stage cancer needing further therapy.

Inclusion Criteria

I had surgery to remove my uterus, ovaries, and fallopian tubes.

I can take care of myself and am up and about more than half of the day.

Willingness and ability to provide written informed consent and to comply with the study protocol as judged by the investigator

Exclusion Criteria

I have had or will have radiation therapy to my pelvic area.

Subject is unable or unwilling to participate in a study-related procedure

I still have side effects from treatments I received over 4 weeks ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4-12 weeks

Radiation

Participants receive HDR vaginal brachytherapy, either 3 fractions of 7 Gy or 6 fractions of 4 Gy

3-6 weeks

3-6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 3 months, 1 year, and 2 years

2 years

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• HDR vaginal brachytherapy

Trial Overview The study compares two standard treatments for sexual dysfunction after endometrial cancer: one group receives high dose radiation vaginal brachytherapy in three sessions (7 Gy each), while another gets six sessions (4 Gy each). The goal is to determine which treatment approach is more effective.

How Is the Trial Designed?

Group I: ARM BA: 3 treatments of 7Gy Active Control 1 Intervention

initially randomized to ARM B but wanted to switch to ARM A of HDR vaginal brachytherapy in 3 treatments (fractions) of 7Gy for a total dose of 21gy

Group II: ARM A: 3 treatments of 7Gy Active Control 1 Intervention

Arm A: accepted randomization to HDR vaginal brachytherapy in 3 treatments (fractions) of 7Gy for a total dose of 21gy

Group III: ARM B: 6 treatment of 4Gy Active Control 1 Intervention

Arm B: accepted randomization to HDR vaginal brachytherapy 6 treatments (fractions) of 4Gy for a total does of 24gy

Group IV: ARM AB: 6 treatment of 4Gy Active Control 1 Intervention

Arm AB: initially randomized to ARM A but wanted to switch to ARM B treatment of HDR vaginal brachytherapy 6 treatments (fractions) of 4Gy for a total does of 24gy

HDR vaginal brachytherapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as HDR Vaginal Brachytherapy for:

• Endometrial cancer
• Cervical cancer
• Vaginal cancer

Approved in United States as HDR Vaginal Brachytherapy for:

• Endometrial cancer
• Cervical cancer
• Vaginal cancer

Approved in Canada as HDR Vaginal Brachytherapy for:

• Endometrial cancer
• Cervical cancer
• Vaginal cancer

Who Is Running the Clinical Trial?

Timothy Showalter, MD

Lead Sponsor

Trials

2

Recruited

290+

Kara Romano, MD

Lead Sponsor

Trials

1

Recruited

260+

Published Research Related to This Trial

Outpatient high-dose-rate (HDR) vaginal cuff brachytherapy (VCB) for low-risk endometrial cancer showed excellent efficacy, with 100% vaginal control rates and a 4-year survival rate of 95% among 191 patients treated over an 8-year period.

The treatment was associated with minimal complications, as there were no acute complications and a 30-day morbidity and mortality rate of 0%, highlighting its safety and convenience compared to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outpatient vaginal cuff brachytherapy for endometrial cancer. Petereit, DG., Tannehill, SP., Grosen, EA., et al.[2022]

Adjuvant high-dose-rate vaginal brachytherapy (HDR VB) with a low-dose scheme (24 Gy in 6 fractions) resulted in excellent clinical outcomes for women with early-stage endometrial adenocarcinoma, showing very low rates of vaginal relapse (1.9%) and high overall survival (98.9%) over a median follow-up of 42 months.

Higher body mass index (BMI) was associated with an increased risk of vaginal relapse, suggesting that patients with higher BMI may need tailored treatment strategies to optimize outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-Dose Adjuvant Cylinder Brachytherapy for Endometrioid Endometrial Cancer. Alban, GM., Buscariollo, DL., Cheng, T., et al.[2020]

The novel direction modulated brachytherapy (DMBT) vaginal cylinder applicator significantly improves dose coverage at the vaginal apex for women with stage I endometrial cancer, addressing the common issue of cold spots caused by anisotropic dose distribution.

This new applicator design allows for deeper dose delivery without increasing peripheral doses, with only a slight increase in treatment time (7-13%), making it a promising advancement for enhancing the efficacy of high-dose-rate brachytherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The design of a novel direction modulated brachytherapy vaginal cylinder applicator for optimizing coverage of the apex. Meftahi, M., Fields, E., Guy, C., et al.[2022]

In a study of 128 patients with intermediate- to high-risk stage I endometrial cancer, vaginal cuff brachytherapy alone resulted in a 5-year overall survival rate of 96% and a disease-free survival rate of 93%, indicating its efficacy as a treatment option.

The treatment was associated with low morbidity, as none of the patients experienced severe complications (grade 3/4), highlighting its safety profile for patients after complete surgical staging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaginal high dose rate brachytherapy alone in patients with intermediate- to high-risk stage I endometrial carcinoma after radical surgery. Atahan, IL., Ozyar, E., Yildiz, F., et al.[2022]

In a study involving 19 endometrial cancer patients, both fractional re-imaging (FRI) and first fraction imaging (FFI) approaches showed no significant difference in mean radiation doses to the bladder, rectum, and bowel during HDR vaginal cuff brachytherapy.

The FFI approach was found to be more cost-effective, saving approximately $663 per patient, while still providing adequate dosimetry, suggesting that fractional re-imaging may only be necessary for patients at risk of exceeding dose limits to critical organs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric and cost comparison of first fraction imaging versus fractional re-imaging on critical organ dose in vaginal cuff brachytherapy. Corso, CD., Jarrio, C., Nunnery, EW., et al.[2016]

The study successfully demonstrated that a new 50kV X-ray point source can create a uniform dose distribution for postoperative intravaginal brachytherapy in endometrial carcinoma, comparable to traditional (192)Ir high-dose rate afterloading techniques.

The method achieved consistent dose delivery at various tissue depths, with a maximum deviation of less than 7% in repeated measurements, indicating its potential reliability and effectiveness as an alternative treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel device for intravaginal electronic brachytherapy. Schneider, F., Fuchs, H., Lorenz, F., et al.[2022]

In a study of 126 patients with stage I intermediate-risk endometrial cancer, high-dose-rate brachytherapy (HDR-BT) delivered in four fractions of 6 Gy resulted in excellent local control with a 3-year local failure rate of only 2.1%.

The mean bladder point dose did not predict acute urinary toxicity, as only 9.5% of patients experienced mild urinary side effects, indicating that HDR-BT is a safe adjuvant treatment option with minimal severe toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bladder (ICRU) dose point does not predict urinary acute toxicity in adjuvant isolated vaginal vault high-dose-rate brachytherapy for intermediate-risk endometrial cancer. Sapienza, LG., Aiza, A., Gomes, MJ., et al.[2020]

The study involving 54 endometrial cancer patients demonstrated that accelerated short course high dose rate intravaginal brachytherapy (HDR IVB) is a safe and well-tolerated treatment, with no severe toxicities reported during the follow-up period.

Vaginal toxicities were more common at 4 and 8 months post-treatment, but interestingly, elderly patients experienced significantly fewer complications compared to younger patients, suggesting that age may influence treatment tolerance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the Incidence Rate of an Accelerated Short Course High Dose Rate Intravaginal Brachytherapy Complications in Patients with Endometrial Cancer. Amouzegar Hashemi, F., Vesgari Kiasari, Z., Kalaghchi, B., et al.[2020]

In a study of 69 women with early-stage endometrial carcinoma, high dose rate (HDR) vaginal brachytherapy showed a 92% disease-free survival rate and a 79% overall survival rate over a median follow-up of 45 months.

The treatment was associated with minimal acute and late side effects, suggesting that HDR brachytherapy is an effective and safe option for preventing vaginal recurrence in endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High dose rate vaginal brachytherapy in early stage endometrial carcinoma: preliminary analysis. Hong, JJ., Yacoub, SF., Blevins, JC., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5148211/

Therapeutic analysis of high-dose-rate 192Ir vaginal cuff ... To evaluate high-dose-rate (HDR) vaginal cuff brachytherapy (VCBT) in the treatment of endometrial cancer in a cylindrical target volume with either a ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5557121/

Vaginal cuff brachytherapy in endometrial cancer The analyses of >132000 patients showed up to a 22% decrease in mortality risk in these patient groups, and postoperative irradiation was an independent factor ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S153847212500073X

Clinical outcomes following brachytherapy for endometrial ... About 30 Gy in 3 fractions prescribed to the cylinder surface demonstrated good tolerability, and favorable outcomes for women with narrow vaginal anatomy who ...

4. ascopubs.org ascopubs.org/doi/10.1200/OA.24.00014

Short-Course Adjuvant Vaginal Cuff Brachytherapy in Early ... Vaginal cuff brachytherapy (VCB) is widely used for adjuvant treatment of endometrial cancer, yet limited randomized data examine the optimal ...

5. practicalradonc.org practicalradonc.org/article/S1879-8500(23)00050-4/fulltext

(Potential) Mishaps of High-Dose-Rate Vaginal Cuff ... Introduction. Vaginal cuff brachytherapy has been consistently shown to decrease endometrial cancer (EMC) recurrence in the proximal vagina, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6335557/

Vaginal toxicity after high-dose-rate endovaginal ... The data suggest that HDR endovaginal brachytherapy, with or without chemotherapy, is very well tolerated with low rates of acute and late vaginal toxicities.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1538472121005274

The role for vaginal cuff brachytherapy boost after external ... This study demonstrated a significant improvement in vaginal/pelvic recurrences with combined therapy having a 5-year recurrence rate of 2.3% vs. 6.8% in VB ...

8. americanbrachytherapy.org americanbrachytherapy.org/ABS/document-server/?cfp=ABS/assets/File/public/consensus-statements/Brachy2.pdf

Compendium of fractionation choices for gynecologic HDR ... ABSTRACT. PURPOSE: The purpose of this study was to report a list of accepted fractionation schemes for high-dose-rate (HDR) brachytherapy for gynecological ...