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

NCT04493333 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 239531
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Vaginal Atrophy; Postmenopausal Symptoms; Breast Cancer Female; Long-term Survivors

Keywords

Postmenopausal; Breast Cancer Survivor; Vaginal

Outcome Measures

Primary Outcomes (1)

• Difference in Vaginal Maturation Index (VMI) Response From Baseline to Week 12

  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.

  Baseline and 12 weeks (±1 week)

Secondary Outcomes (6)

• Difference in Vaginal pH From Baseline to Week 12

  12 weeks (±1 week)

• Difference in Dyspareunia Scores on the Brief Sexual Symptom Checklist for Women (BSSC-W) From Baseline to Week 12

  12 weeks (±1 week)

• Difference in Vaginal Dryness Scores on the Brief Sexual Symptom Checklist for Women (BSSC-W) From Baseline to Week 12

  12 weeks (±1 week)

• Difference in Dyspareunia Subscale Scores on the Female Sexual Dysfunction Index (FSFI) From Baseline to Week 12

  12 weeks (±1 week)

• Difference in Vaginal Dryness Subscale Scores on the Female Sexual Dysfunction Index (FSFI) From Baseline to Week 12

  12 weeks (±1 week)

Study Arms (2)

Vaginal DHEA

EXPERIMENTAL

Vaginal insert with 6.5 mg vaginal DHEA self-administered once daily at bedtime for 12 weeks

Drug: Vaginal Dehydroepiandrosterone

Vaginal Polycarbophil Moisturizer

ACTIVE COMPARATOR

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

Interventions

Vaginal Dehydroepiandrosterone DRUG

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.

Also known as: Intrarosa®, Vaginal DHEA, Prasterone

Vaginal DHEA

Vaginal Polycarbophil Moisturizer COMBINATION_PRODUCT

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.

Also known as: Replens™

Vaginal Polycarbophil Moisturizer

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Arkansas: lead
• AMAG Pharmaceuticals, Inc.: collaborator

Study Sites (1)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

MeSH Terms

Interventions

Dehydroepiandrosterone; Replens

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 17-Ketosteroids; Ketosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Limitations and Caveats

Early termination due to low enrollment and lack of subject participation/noncompliance.

Results Point of Contact

• Title: I-Shin Wen
• Organization: University of Arkansas for Medical Sciences

iwen@uams.edu

5016868274

Study Officials

• Gloria Richard-Davis, MD

  University of Arkansas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The cytologist's reading specimens will be blinded.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 27, 2020
• First Posted: July 30, 2020
• Study Start: June 7, 2021
• Primary Completion: July 18, 2023
• Study Completion: July 18, 2023
• Last Updated: November 27, 2024
• Results First Posted: September 23, 2024

Record last verified: 2024-09

Locations

US (1)