Vaginal Dehydroepiandrosterone (DHEA) in Postmenopausal Breast Cancer Survivors on Aromatase Inhibitors

Phase 2

Terminated

Conditions: Long-term Survivors
Postmenopausal Symptoms
Breast Cancer Female
Vaginal Atrophy

Interventions: Combination Product: Vaginal Polycarbophil Moisturizer
Drug: Vaginal Dehydroepiandrosterone

Registration Number: NCT04493333

Lead Sponsor: University of Arkansas

Brief Summary: The purpose of this research is to gather information on the safety and effectiveness of Intrarosa®, also known as Dehydroepiandrosterone (DHEA), and prasterone. By doing this study, the investigators hope to learn if Intrarosa® can improve vaginal discomfort. Participants will be assigned to one of two groups. One group will use Intrarosa® once a day. The other group will use Replens™ two times a week.

Detailed Description: This will be a two-armed, randomized Phase II trial. All study subjects will be asked to fill out a simple 5-question sexual functioning survey. If any concern about sexual functioning is noted, the subject will also be asked to fill out a more extensive Sexual functioning tool, to help determine which domain of sexual functioning is the most bothersome.

Subjects who complete the initial screening will be randomly assigned to the Intrarosa® or Replens™ arm by a 1:1 ratio. Subjects randomized to the Intrarosa® arm will use 6.5 mg daily for 12 weeks (±1 week). Subjects randomized to the Replens™ arm will use a vaginal applicator two times per week for 12 weeks.

At baseline and at 12 weeks, subjects will undergo a physical exam including clinical breast and gynecological exam. During gynecologic exams, the vaginal Potential of Hydrogen (pH) will be determined and a swab of vaginal epithelium sent for determination of the Vaginal Maturation Index (VMI) and Maturation Value (MV). These will be used as objective physiologic markers to determine the improvement in vaginal atrophy. The cytologist's reading specimens will be blinded.

Additionally, all study subjects will be asked to fill out questionnaires at baseline and again in 12 weeks.

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 8

Inclusion Criteria

Postmenopausal patients with a history of breast cancer who have completed primary treatment with curative intent, who have been on an aromatase inhibitors (AI) for at least 6 months
Stage I-III, hormone receptor positive breast cancer regardless of human epidermal growth factor receptor 2 (HER2) status
Postmenopause defined as 12 months of spontaneous amenorrhea, or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels > 40 mIU/mL (milli-international units per milliliter), or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy. FSH level will be documented on all subjects.
Patients reporting any symptoms of vaginal dryness or dyspareunia as assessed by the Brief Sexual Symptom Checklist for Women (BSSC-W) or the Female Sexual Function Index (FSFI)
No evidence of active malignant breast or gynecologic disease
Absence of undiagnosed, persistent or recurring genital bleeding that has not been evaluated to determine the cause [6]
No planned changes in AI during the study period
Mammogram (if appropriate, as determined by the treating physician and will be documented) within 12 months of study entry
Patients with documented normal Pap within 12 months of study entry

Exclusion Criteria

Use of any estrogen or progesterone depot-preparation drug or progestin implant in the last 6 months before study entry
Use of any androgen or anabolic steroids in the last 6 months before study entry
Use of any oral or transdermal hormonal products (estrogen, progestin, or DHEA) within the last 8 weeks prior to study entry; however, a subject can elect to wait for an 8-week washout period before study entry.
Use of any vaginal or intrauterine hormonal products in the last 8 weeks; however, a subject can elect to wait for an 8-week washout before study entry.
Use of any natural over the counter estrogenic products in the last 6 months; however, a subject can elect to wait for a 6-month washout before study entry.
Concomitant vulvar and vaginal surgical or laser treatments
Vaginal infection or confounding vulvar or active vaginal disease process
Prior radiation to the pelvis or history of gynecologic cancer
Inability to tolerate a vaginal/speculum exam
Undiagnosed, persistent or recurring genital bleeding or other indication of active pelvic disease process that has not been evaluated [6]
Clinically significant uncontrolled depression or severe psychiatric symptoms
If subject has an established routine of inert vaginal lubricant use for routine or occasional relief of vulvar or vaginal symptoms prior to the study period, it may be continued during the study period along with the study drug.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vaginal Polycarbophil Moisturizer	Vaginal Polycarbophil Moisturizer	Prefilled vaginal applicator with 2.5 g of polycarbophil vaginal moisturizing gel, self-administered two times per week at night for 12 weeks
Vaginal DHEA	Vaginal Dehydroepiandrosterone	Vaginal insert with 6.5 mg vaginal DHEA self-administered once daily at bedtime for 12 weeks

Primary Outcome Measures

Name	Time	Method
Difference in Vaginal Maturation Index (VMI) Response From Baseline to Week 12	Baseline and 12 weeks (±1 week)	The change in the subject's calculated VMI from baseline to the end of treatment at 12 weeks (±1 week). VMI = 1.0 x %S + 0.5 x %I + 0.0 x %P cells, which is the same as VMI = %S + (0.5 x %I) when simplified. It has a potential range of 0-100. A VMI of 65-100 suggests a normal premenopausal environment, 50-64 indicates a moderate estrogenic effect, and \< 50 indicates atrophy.

Secondary Outcome Measures

Name	Time	Method
Difference in Vaginal pH From Baseline to Week 12	12 weeks (±1 week)	Vaginal pH was used as an objective physiologic marker to determine the improvement in vaginal atrophy. pH is a measure of acidity and alkalinity and can range from 0 to 14, with 7 being neutral. Lower pH scores are acidic and higher pH scores are basic or alkaline. A normal healthy vaginal pH is 4.5. As the vaginal epithelium becomes thinner and more atrophic, the mucosa has less glycogen content and less lactobacilli to convert the glycogen into lactic acid, which results in an increase in the vaginal pH.
Difference in Dyspareunia Scores on the Brief Sexual Symptom Checklist for Women (BSSC-W) From Baseline to Week 12	12 weeks (±1 week)	The Dyspareunia Score on the BSSC-W asks if there is a problem with pain during sex. A difference score of 0 indicated no change in whether it was a problem. The min and max are both 0 which makes the range also 0. Only 2 participants had week 12 scores. These scores were both 1. (So the min and max were 1 with the range being 0.) Of the baseline scores, these 2 participants both had scores of 1 again. (So the min and max for these 2 participants were both 1 with a range of 0.) If we include these 2 participants with the other 6 who have baseline dyspareunia scores on the BSSC-W, then 7 participants has a score of 1 and 1 participant had a score of 0. This would make the min, max, and range 0, 1, and 1 respectively. As for which value represents a better or worse outcome, 1 indicates presence of dyspareunia while 0 indicates absence of dyspareunia, so 1 is a worse outcome than 0. Subscales are not combined here to produce a total score.
Difference in Vaginal Dryness Scores on the Brief Sexual Symptom Checklist for Women (BSSC-W) From Baseline to Week 12	12 weeks (±1 week)	The min and the max are both 0 which make the range also 0. These were obtained from subtracting each participant's score at baseline from their score at week 12. Only 2 participants had week 12 scores. These scores were both 1. Of the baseline scores, these 2 participants both had scores of 1 again. If 2 participants with the other 6 have baseline dyspareunia scores on the BSSC-W, then 7 participants have a score of 1 and 1 participant had a score of 0. This would make the min, max, and range 0, 1, and 1 respectively. As for which value represents a better or worse outcome, 1 indicates presence of vaginal dryness (problem with decreased vaginal lubrication) while 0 indicates absence of vaginal dryness (or an absence of this problem of decreased vaginal lubrication), so 1 is a worse outcome than 0. Subscales are not combined here to produce a total score.
Difference in Dyspareunia Subscale Scores on the Female Sexual Dysfunction Index (FSFI) From Baseline to Week 12	12 weeks (±1 week)	The Dyspareunia Subscale Score on the Female Sexual Dysfunction Index ranges from 0-5 with higher scores indicating better sexual function, so less dyspareunia.
Difference in Vaginal Dryness Subscale Scores on the Female Sexual Dysfunction Index (FSFI) From Baseline to Week 12	12 weeks (±1 week)	The Vaginal Dryness (or Lubrication) Subscale Score on the Female Sexual Dysfunction Index ranges from 0-5 with higher scores indicating better sexual function, so more lubrication.
Difference in Quality of Life on the Quality of Life - Cancer Survivor Version (QOL-CSV) From Baseline to Week 12	12 weeks (±1 week)	The Quality of Life - Cancer Survivor Version ranges from 0-10 with higher scores indicating a higher quality of life. T here are only 2 difference scores for each of the 4 subscales. The min, max, and ranges of these Well-Being Subscales: Physical -1.00, -0.62, and 0.38. Psychological -0.72, 0.94, and 1.67. Social 0.75, 1.25, and 0.50. Spiritual -1.57, 3.29, and 4.86. For Psychological the min, max, and range are 2.61, 6.83, and 4.22. For Social the min, max, and range are 2.63, 7.38, and 4.75. For Spiritual the min, max, and range are 4.43, 8.43, and 4.00. A negative difference score indicates a worsening of quality of life while a positive score indicates that qualify of life got better. Subscales were not combined here to produce a total score. For the baseline and week 12 scores on the QOL-CSV, higher scores mean higher quality of life.