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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to see the effects of two different standard of care treatments of endometrial cancer on sexual dysfunction. This study will compare two standard of care treatments: HDR (high dose radiation) vaginal brachytherapy 3 fractions of 7 Gy to HDR vaginal brachytherapy 6 fractions of 4Gy for early stage endometrial cancer.

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.

What data supports the effectiveness of the treatment Vaginal Brachytherapy for Endometrial Cancer?

Research shows that high-dose-rate vaginal brachytherapy is effective in preventing cancer recurrence in women with early-stage endometrial cancer, with a 5-year disease-free survival rate of 92% and minimal side effects. Another study found a 5-year overall survival rate of 96% and disease-free survival of 93% in patients treated with this therapy, indicating it is a successful treatment option with low complication rates. ^{1 2 3 4 5}

Is vaginal brachytherapy safe for humans?

Vaginal brachytherapy, including high-dose-rate (HDR) versions, has been shown to be generally safe for humans, with studies reporting minimal complications and no severe toxicities in patients with endometrial cancer. Some mild side effects may occur, but overall, it is well tolerated. ^{1 3 6 7 8}

How does HDR vaginal brachytherapy differ from other treatments for endometrial cancer?

HDR vaginal brachytherapy is unique because it delivers a high dose of radiation directly to the vaginal area in a short amount of time, reducing the need for prolonged hospital stays and minimizing side effects compared to traditional radiation therapies. It is particularly effective in preventing cancer recurrence in the vaginal area after surgery, offering a convenient and cost-effective alternative to other radiation treatments. ^{1 2 3 7 9}

Research Team

Kara Romano, MD

Principal Investigator

University of Virginia

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

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 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]

References

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

High dose rate vaginal brachytherapy in early stage endometrial carcinoma: preliminary analysis. [2022]

2. England 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. [2022]

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

The design of a novel direction modulated brachytherapy vaginal cylinder applicator for optimizing coverage of the apex. [2022]

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

Low-Dose Adjuvant Cylinder Brachytherapy for Endometrioid Endometrial Cancer. [2020]

5. United States 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. [2016]

6. Thailand 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. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Outpatient vaginal cuff brachytherapy for endometrial cancer. [2022]

8. Poland 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. [2020]

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

A novel device for intravaginal electronic brachytherapy. [2022]