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

• ClinicalTrials.gov Identifier: NCT04493333
• Recruitment Status: Recruiting
• First Posted: July 30, 2020
• Last Update Posted: June 9, 2022
• Sponsor: University of Arkansas
• Collaborator: AMAG Pharmaceuticals, Inc.
• Information provided by (Responsible Party): University of Arkansas

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Vaginal Atrophy; Postmenopausal Symptoms; Breast Cancer Female; Long-term Survivors	Drug: Vaginal Dehydroepiandrosterone; Combination Product: Vaginal Polycarbophil Moisturizer	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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.
• Masking: Single (Outcomes Assessor)
• Masking Description: The cytologist's reading specimens will be blinded.
• Primary Purpose: Supportive Care
• 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
• Actual Study Start Date: June 7, 2021
• Estimated Primary Completion Date: June 2023
• Estimated Study Completion Date: June 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Vaginal DHEA; Vaginal insert with 6.5 mg vaginal DHEA self-administered once daily at bedtime for 12 weeks	Drug: Vaginal Dehydroepiandrosterone; This is a vaginally administered suppository steroid indicated for the treatment of moderate to severe dyspareunia, a frequent symptom of vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause.; Other Names: Intrarosa®; Vaginal DHEA; Prasterone
Active Comparator: 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	Combination Product: Vaginal Polycarbophil Moisturizer; This is an FDA cleared, over-the-counter personal lubricant for vaginal application, intended to moisturize and lubricate, to enhance the ease and comfort of intimate sexual activity and supplement the body's natural lubrication. It is non-sterile, water-based, non-irritating, non-greasy, non-staining vaginal gel delivered as a long-lasting moisturizer for vaginal dryness.; Other Name: Replens™

Outcome Measures

Primary Outcome Measures :

1. Change in vaginal atrophy [ Time Frame: 12 weeks ]
   Improvement of the vaginal maturation index (VMI) calculated based on the decrease of the percentage of the parabasal cells and the increase of the sum of the percentages of the intermediate and superficial cells

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Joseph A Holley; 501-686-8274; JAHolley@uams.edu

Locations

United States, Arkansas

University of Arkansas for Medical Sciences; Recruiting

Little Rock, Arkansas, United States, 72205

Contact: Matthew Kovak, MS 501-686-8274 mrkovak@uams.edu

Principal Investigator: Gloria Richard-Davis, MD

Sponsors and Collaborators

University of Arkansas

AMAG Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Gloria Richard-Davis, MD; University of Arkansas

More Information

• Responsible Party: University of Arkansas
• ClinicalTrials.gov Identifier: NCT04493333
• Other Study ID Numbers: 239531
• First Posted: July 30, 2020
• Last Update Posted: June 9, 2022
• Last Verified: June 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Arkansas:

Postmenopausal; Breast Cancer Survivor; Vaginal

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Calcium polycarbophil; Psyllium; Dehydroepiandrosterone; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs; Antidiarrheals; Gastrointestinal Agents; Cathartics