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

Trial Summary

What is the purpose of this trial?

This randomized phase III trial studies short course vaginal cuff brachytherapy to see how well it works compared with standard of care vaginal cuff brachytherapy in treating participants with stage I-II endometrial cancer. Short course vaginal cuff brachytherapy, also known as internal radiation therapy, uses (over a shorter period) radioactive material placed directly into or near a tumor in the upper portion of the vagina to kill tumor cells. After completion of cohort 1 (108 participants), the protocol was expended to add a second cohort of 80 additional participants, and re-opened study recruitment.

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 data supports the effectiveness of the treatment Vaginal Cuff Brachytherapy for Uterine Cancer?

Research shows that vaginal cuff brachytherapy is effective in controlling disease with minimal side effects for early-stage endometrial cancer, and it is as effective as external beam radiation in preventing cancer recurrence. The SAVE trial's early results are promising, suggesting that a shorter treatment regimen may be a viable option. ^{1 2 3 4 5}

Is vaginal cuff brachytherapy generally safe for humans?

Vaginal cuff brachytherapy is generally considered safe, with studies showing it results in excellent disease control and minimal toxicity for endometrial cancer. It has been found to cause less late toxicity compared to external beam radiation therapy, although there is a risk of vaginal stenosis (narrowing of the vagina) after treatment. ^{1 5 6 7 8}

How is vaginal cuff brachytherapy different from other treatments for uterine cancer?

Vaginal cuff brachytherapy is unique because it delivers high-dose radiation directly to the site where the uterus was removed, minimizing exposure to surrounding tissues. This internal radiation therapy is often used after surgery to prevent cancer recurrence and can be administered in a shorter course compared to traditional external beam radiation, offering effective disease control with minimal side effects. ^{1 3 5 7 8}

Research Team

Cristina DeCesaris

Principal Investigator

Huntsman Cancer Institute/ University of Utah

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Vaginal cuff brachytherapy for endometrial cancer: a review of major clinical trials with a focus on fractionation. [2022]

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

Time-driven activity-based costing of adjuvant vaginal cuff brachytherapy for uterine cancer in an integrated brachytherapy suite. [2022]

3. United States 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. [2022]

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

The role for vaginal cuff brachytherapy boost after external beam radiation therapy in endometrial cancer. [2022]

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

Predictors of vaginal stenosis after intravaginal high-dose-rate brachytherapy for endometrial carcinoma. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Vaginal cuff brachytherapy in endometrial cancer - a technically easy treatment? [2020]

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

A new short daily brachytherapy schedule in postoperative endometrial carcinoma. Preliminary results. [2022]

8. 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]