Vaginal Cuff Brachytherapy for Uterine Cancer

(SAVE Trial)

Recruiting at 2 trial locations

Overseen By Rachel Kingsford

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Utah

Disqualifiers: Other cancer stages, Previous pelvic radiotherapy, Long interval post-hysterectomy

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: 3

Duration: 2-3 weeks

188 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for stage I-II endometrial cancer, which affects the uterine lining. It compares a shorter course of internal radiation therapy, where radioactive material is placed directly near the tumor, to the usual longer treatment. The goal is to determine if the shorter treatment is as effective as the standard one. This trial is for individuals who have undergone a hysterectomy, have no remaining cancer, and require vaginal cuff brachytherapy, which targets the top of the vagina with radiation. As a Phase 3 trial, this research represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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.

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

Research has shown that short course vaginal cuff brachytherapy, a type of internal radiation therapy, is generally safe and well-tolerated for treating early-stage endometrial cancer. One study found that this shorter treatment schedule does not increase short-term side effects compared to the standard treatment. Another study demonstrated that patients experience similar cancer control with minimal side effects. Additionally, research supports its safety, indicating a low rate of complications. Overall, the evidence suggests that this approach is a promising and safe option for managing endometrial cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for uterine cancer?

Researchers are excited about short course vaginal cuff brachytherapy for uterine cancer because it offers a potentially quicker and more convenient treatment option. Unlike the standard of care, which involves 3-5 sessions over as many as three weeks, this new approach administers treatment in just two sessions spaced one week apart. This could make the treatment less burdensome for patients both in terms of time and logistical challenges, while still aiming to maintain effectiveness.

What evidence suggests that short course vaginal cuff brachytherapy is effective for uterine cancer?

Research has shown that a shorter course of vaginal cuff brachytherapy, which participants in this trial may receive, works as effectively as the usual longer treatment for early-stage endometrial cancer. This method delivers higher doses of radiation over a shorter period and effectively controls cancer. Patients who received this shorter treatment reported a similar quality of life and manageable side effects. These findings suggest that this shorter treatment could serve as a good alternative to the standard approach, offering the same cancer control with potentially greater convenience. ^{1 2 3 6 7}

Who Is on the Research Team?

Cristina DeCesaris

Principal Investigator

Huntsman Cancer Institute/ University of Utah

Are You a Good Fit for This Trial?

This trial is for patients with stage I-II endometrial cancer who have had a hysterectomy and no remaining disease. It's open to those with a life expectancy over 2 years, specific types of tumors (endometrioid, serous, clear cell), including carcinosarcoma. Participants must be able to consent and have an ECOG-performance status of 0-2.

Inclusion Criteria

I can take care of myself and perform daily activities.

My cancer is a specific type of endometrial carcinoma and may require a special radiation treatment.

You are expected to live for more than 2 years.

Exclusion Criteria

More than 16 weeks have passed since my hysterectomy.

My endometrial cancer is not in the specified stages.

I have had radiation therapy to my pelvic area before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo vaginal cuff brachytherapy. Arm I: Short course for 2 fractions with 1 week apart. Arm II: Standard of care for 3-5 fractions over no more than 3 weeks.

2-3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up visits occur at 1, 6, and 12 months.

12 months

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Short course vaginal cuff brachytherapy

Trial Overview The study compares short course vaginal cuff brachytherapy—a type of internal radiation therapy given over a shorter period—with the standard treatment duration. The goal is to see which method works better for treating upper vagina tumors in endometrial cancer patients.

How Is the Trial Designed?

Group I: Short course vaginal cuff brachytherapy Experimental Treatment 1 Intervention

Participants undergo short course vaginal cuff brachytherapy for 2 fractions with 1 week apart.

Group II: Vaginal cuff brachytherapy Active Control 1 Intervention

Participants undergo standard of care vaginal cuff brachytherapy for 3-5 fractions over no more than 3 weeks.

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

Approved in European Union as Vaginal Cuff Brachytherapy for:

• Endometrial cancer
• Uterine cancer
• Vaginal cancer

Approved in United States as Vaginal Cuff Brachytherapy for:

• Endometrial cancer
• Uterine cancer
• Vaginal cancer

Approved in Canada as Vaginal Cuff Brachytherapy for:

• Endometrial cancer
• Uterine cancer
• Vaginal cancer

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Published Research Related to This Trial

Adjuvant vaginal cuff brachytherapy is effective in reducing local recurrence in endometrial cancer, with treatment regimens varying from three to six fractions, but both are well tolerated by patients.

A cost analysis showed that delivering six fractions of treatment costs $2,227 compared to $1,415 for three fractions, indicating a 57% increase in costs, primarily driven by personnel expenses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time-driven activity-based costing of adjuvant vaginal cuff brachytherapy for uterine cancer in an integrated brachytherapy suite. Su, L., Dutta, SW., Sanders, JC., et al.[2022]

In a study of 101 patients treated with intravaginal high-dose-rate brachytherapy for endometrial carcinoma, those who received a higher total dose (>14 Gy) and had a larger proportion of the vagina treated (>60%) were more likely to develop vaginal stenosis (VS) of Grade ≥1.

Consistent use of vaginal dilators was found to be protective against more severe vaginal stenosis (Grade ≥2), suggesting that post-treatment care can help mitigate this side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of vaginal stenosis after intravaginal high-dose-rate brachytherapy for endometrial carcinoma. Park, HS., Ratner, ES., Lucarelli, L., 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]

In a study of 102 patients with endometrial carcinoma, a short brachytherapy schedule showed no vaginal-cuff relapses (VCR) during an average follow-up of about 29 months, indicating its efficacy in preventing cancer recurrence.

Late toxicity was relatively low, with vaginal toxicity occurring in 24.32% of patients in one treatment group and 21.4% in another, while rectal toxicity was only seen in 2.7%, suggesting that the treatment is safe with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new short daily brachytherapy schedule in postoperative endometrial carcinoma. Preliminary results. Rovirosa, Á., Ascaso, C., Herreros, A., et al.[2022]

A systematic review of 21 studies indicates that vaginal cuff brachytherapy (VB) can enhance local control and survival in endometrial cancer patients at higher risk of vaginal recurrence, particularly those with cervical stromal involvement in select Stage III cases.

While there is limited prospective evidence, the findings suggest that individual risk factors such as tumor grade, histology, and margin status should be considered when deciding to add a VB boost to external beam radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role for vaginal cuff brachytherapy boost after external beam radiation therapy in endometrial cancer. Griffith, T., Nwachukwu, C., Albuquerque, K., et al.[2022]

Vaginal cuff brachytherapy is an effective adjuvant treatment for early-stage endometrial cancer, providing excellent disease control with minimal toxicity, as supported by the PORTEC-2 trial which showed it is non-inferior to external beam radiation for preventing vaginal recurrence.

The ongoing SAVE trial is exploring a two-fraction regimen of vaginal cuff brachytherapy, and early results are promising, suggesting this approach may become a viable option in the management of endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaginal cuff brachytherapy for endometrial cancer: a review of major clinical trials with a focus on fractionation. Parsons, MW., Huang, YJ., Burt, L., et al.[2022]

In a study of 601 patients with high-risk early-stage endometrial carcinoma, vaginal cuff brachytherapy combined with chemotherapy (VCB/C) did not show superior recurrence-free survival compared to pelvic radiation therapy (RT), with both treatments having a 60-month RFS of 76%.

VCB/C was associated with higher acute toxicity and a greater rate of pelvic or para-aortic nodal recurrences (9% vs. 4% for RT), suggesting that pelvic RT remains a safer and effective treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III Trial: Adjuvant Pelvic Radiation Therapy Versus Vaginal Brachytherapy Plus Paclitaxel/Carboplatin in High-Intermediate and High-Risk Early Stage Endometrial Cancer. Randall, ME., Filiaci, V., McMeekin, DS., et al.[2022]

Vaginal cuff brachytherapy (VCB) is an effective postoperative treatment for high- to intermediate-risk endometrial cancer, showing similar relapse reduction compared to external beam radiotherapy (EBRT) but with less late toxicity, as demonstrated by the PORTEC-2 trial.

The review emphasizes the importance of both patient selection based on risk categories and technical aspects of the VCB procedure, such as bladder and rectal distension and applicator positioning, which can significantly influence treatment outcomes and toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaginal cuff brachytherapy in endometrial cancer - a technically easy treatment? Sabater, S., Andres, I., Lopez-Honrubia, V., et al.[2020]

Citations

1. healthcare.utah.edu healthcare.utah.edu/huntsmancancerinstitute/press-releases/2025/02/short-course-radiation-therapy-effective-endometrial-cancer-patients

Short-Course Radiation Therapy Effective for Endometrial ... Short-course, higher dose vaginal brachytherapy for endometrial cancer had similar effectiveness to more frequent, lower dose sessions.

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

Short-Course Adjuvant Vaginal Cuff Brachytherapy in Early ... Short-course VCB has noninferior short-term quality of life compared with standard regimens with acceptable short-term acute toxicity and cancer control ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24006005

Review Vaginal cuff brachytherapy for endometrial cancer Adjuvant vaginal cuff brachytherapy for early-stage endometrial cancer results in excellent disease control with minimal toxicity. The PORTEC-2 trial showed ...

4. appliedradiationoncology.com appliedradiationoncology.com/articles/short-course-high-dose-brachytherapy-effective-for-endometrial-cancer

Short-Course, High-Dose Brachytherapy Effective for ... In a randomized clinical trial, researchers have found that short-course, higher dose vaginal brachytherapy for endometrial cancer had ...

5. ascopost.com ascopost.com/news/february-2025/short-vs-standard-course-radiation-therapy-for-endometrial-cancer/

Short- vs Standard-Course Radiation Therapy for ... Short-course, higher-dose vaginal brachytherapy for endometrial cancer may demonstrate comparable efficacy to more frequent, lower-dose ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6745200/

Evaluating the Incidence Rate of an Accelerated Short ... Overall, the accelerated HDR IVB was safe and was well tolerated in endometrial cancer patients and the incidence rate of undue complications were equal, if not ...

7. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/98/NCT03422198/Prot_SAP_000.pdf

Short Course Adjuvant Vaginal Cuff Brachytherapy (VCB) ... 9 The 10-year local regional relapse rates were 5% in the external beam group and 14% in the control group for a highly statistical advantage for Page 9 ...