Clinical trial NCT04493333: Vaginal Dehydroepiandrosterone (DHEA) in Postmenopausal Breast Cancer Survivors on Aromatase Inhibitors
Official title: Comparison of Vaginal Dehydroepiandrosterone (DHEA) to Control for Treatment of Vaginal Symptoms in Postmenopausal Breast Cancer Survivors on Aromatase Inhibitors: A Phase II Randomized Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Vaginal Atrophy
Postmenopausal Symptoms
Breast Cancer Female
Long-term Survivors
Keywords: Postmenopausal
Breast Cancer Survivor
Vaginal
Lead sponsor: University of Arkansas
Sponsor class: OTHER
Collaborators: name: AMAG Pharmaceuticals, Inc.
First posted: 2020-07-30
Enrollment: 8
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects are 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.
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Difference in Vaginal Maturation Index (VMI) Response From Baseline to Week 12
timeFrame: Baseline and 12 weeks (±1 week)
Secondary outcomes:
measure: Difference in Vaginal pH From Baseline to Week 12
timeFrame: 12 weeks (±1 week)
measure: Difference in Dyspareunia Scores on the Brief Sexual Symptom Checklist for Women (BSSC-W) From Baseline to Week 12
timeFrame: 12 weeks (±1 week)
measure: Difference in Vaginal Dryness Scores on the Brief Sexual Symptom Checklist for Women (BSSC-W) From Baseline to Week 12
timeFrame: 12 weeks (±1 week)
measure: Difference in Dyspareunia Subscale Scores on the Female Sexual Dysfunction Index (FSFI) From Baseline to Week 12
timeFrame: 12 weeks (±1 week)
measure: Difference in Vaginal Dryness Subscale Scores on the Female Sexual Dysfunction Index (FSFI) From Baseline to Week 12
timeFrame: 12 weeks (±1 week)
measure: Difference in Quality of Life on the Quality of Life - Cancer Survivor Version (QOL-CSV) From Baseline to Week 12
timeFrame: 12 weeks (±1 week)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
Study officials:
affiliation: University of Arkansas
name: Gloria Richard-Davis, MD
role: PRINCIPAL_INVESTIGATOR
References: