Prasterone (Dehydroepiandrosterone) in Treating Postmenopausal Cancer Survivors With Vaginal Symptoms

Study Overview
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Brief Summary
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RATIONALE: Dehydroepiandrosterone (DHEA) may help relieve vaginal symptoms in female cancer survivors. PURPOSE: This randomized phase III trial studies DHEA to see how well it works compared to placebo in treating postmenopausal cancer survivors with vaginal symptoms.

Detailed Description
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Primary Goal: To determine the effectiveness of two doses of daily vaginal prasterone (dehydroepiandrosterone [DHEA]) versus placebo for alleviation of the most bothersome vaginal symptom (vaginal dryness or dyspareunia) over 12 weeks. Exploratory Goals: To evaluate any toxicities arising from DHEA in this patient population. (Exploratory) To evaluate the impact of vaginal DHEA on negative sexual thoughts, sexual function and urologic symptoms. (Exploratory) To explore the role of psychologic (mood, stress), physical (demographics and treatment variables) and situational factors (partner variables and fatigue) as predictors of vaginal dryness and performance outcomes at baseline and at various endpoints throughout the study. (Exploratory) To explore the characteristics of vaginal atrophy and the relationship between vaginal atrophy and quality-of-life questionnaire responses and exposure to hormonal therapy (tamoxifen, exemestane, anastrozole, or letrozole). (Exploratory) To examine the effects of the use of open-label vaginal DHEA gel over 8 weeks in women completing the placebo gel arm of the randomized trial. (Exploratory) Correlative Research Goals: To evaluate the impact of vaginal DHEA on maturation index and pH (select institutions). To evaluate the impact of vaginal DHEA on sex steroid concentrations (estradiol, free testosterone, estrone, and DHEA-S) and markers of bone turnover (osteocalcin and bone alkaline phosphatase). (Correlative) As part of ongoing research for NCCTG Cancer Control studies, we are banking blood products for future studies. (Correlative) OUTLINE: This is a multicenter study. Patients are stratified according to current tamoxifen therapy (yes vs no), concurrent aromatase inhibitor use (anastrozole/letrozole vs exemestane vs none), hysterectomy (yes vs no), and cigarette smoking (current vs past vs never). Patients are randomized to 1 of 3 treatment arms, patients receive low dose vaginal DHEA, high dose vaginal DHEA or vaginal placebo gel. Participants may complete the Profile of Mood States (POMS), the Perceived Stress Scale (PSS), the Fatigue: Vitality subscale of the SF-36, the Vaginal Symptom Quality Questionnaire, the DHEA Side Effect Questionnaire, the Female Sexual Function Index (FSFI), the Sexually Related Intrusive Thoughts - ITS, Impact of Treatment Scale, the Urogenital Atrophy Questionnaire, and the Subject Global Impression of Change at baseline and periodically during study.

Official Title
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Vaginal DHEA for Vaginal Symptoms: A Phase III Randomized, Double Blind, Placebo- Controlled Trial

Conditions
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Breast Cancer, Gynecologic Cancer

Intervention / Treatment
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* Drug: prasterone
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Postmenopausal women with a history of breast or gynecologic cancer (currently no evidence of disease). Note: Postmenopausal status will be determined by the following criteria: 12 months without a period or bilateral oophorectomy or complete chemical ovarian suppression for the past 12 months with continued suppression planned throughout the course of the study menopausal status will be determined by an FSH and an estradiol value in the postmenopausal range (generally FSH > 40IU/L and estradiol < 10 pg/ml, depending on laboratory) if: 9 months without a period or post hysterectomy with at least one ovary remaining and less than 55 years old. Note: if age 55 or older with these criteria, then menopausal status does not need to be determined by labs Significant vaginal complaints. Note: Defined as persistent vaginal dryness and/or pain with intercourse (dyspareunia) of sufficient severity to make a patient desire therapeutic intervention. Eligibility questionnaire response must be moderate or worse levels of severity on one of the two symptoms, either dryness or dyspareunia. The protocol contains more information. Vaginal symptoms must have been present ≥ 2 months prior to randomization. Life expectancy > 12 months. Ability to complete questionnaires by themselves or with assistance. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1. The patient must provide informed written consent. Willing to return to the enrolling institution for follow-up. Willing to provide blood samples for correlative research purposes. Exclusion Criteria: Initiation or discontinuation of tamoxifen or aromatase inhibitors ≤ 2 months prior to randomization or plans to initiate or discontinue any of these medications during the 12-week study. Current diagnosis of an active vaginal infection, if symptoms of vaginal infection, this must be ruled out (ie, foul discharge, fever). Concurrent chemotherapy (long term adjuvant herceptin, lapatanib, and/or bevacizumab is allowed. Planned use of any vaginal preparations during the study period (including any over the counter or herbal preparations). Note: Water-based lubricants (such as KY jelly) are allowed during sexual intercourse. Use of any daily non-hormonal vaginal preparations ≤ 1 week prior to study entry. Exception: Daily water-based lubricants for sexual intercourse. Note: Patients who stop agent may be enrolled after one week. Current (≤ 4 weeks prior to randomization), or planned during the study period, use of any estrogen product or any kind of hormonal vaginal product including bioidentical hormones, estriol or any androgen product. Use of pharmacologic soy or phytoestrogen preparations (Dietary intake of soy - ie milk is acceptable). On a placebo controlled trial for endocrine therapy. Prior or concurrent pelvic radiation therapy. Prior radical pelvic surgery, specifically vaginectomy or pelvic exenteration (TAH/BSO) is allowed). Diagnosis of any of the following conditions within the past five years: Essential vulvodynia Vulvar vestibulitis Bartholin cyst/abscess History of Bartholin gland surgery Lichen sclerosis Lichen planus of the vulvovaginal region Desquamative vaginitis History or current diagnosis of any of the following conditions: Vulvar or vaginal dysplasia Vaginal prolapse Women of childbearing potential, premenopausal women.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I low dose DHEA<br>Participants apply a low dose (3.25 mg) of vaginal prasterone (dehydroepiandrosterone [DHEA]) gel once daily (QD), at bed time, for 12 weeks. Treatment continues until unacceptable adverse events or patient refusal to continue participation on the study. | Drug: prasterone<br>* Applied vaginally<br>|
| Experimental: Arm II high dose DHEA<br>Participants apply a high dose (6.5 mg) of vaginal DHEA gel QD, at bed time, for 12 weeks. Treatment continues until unacceptable adverse events or patient refusal to continue participation on the study. | Drug: prasterone<br>* Applied vaginally<br>|
| Placebo Comparator: Arm III placebo<br>Participants apply a vaginal placebo gel QD, at bed time, for 12 weeks. There is an Optional Continuation Phase (for placebo arm only): Participants apply a high dose of vaginal DHEA gel QD, at bed time, for 12 weeks. Treatment continues until unacceptable adverse events or patient refusal to continue participation on the study. | Other: placebo<br>* Applied vaginally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alleviation of the Most Bothersome Vaginal Symptom (Vaginal Dryness or Dyspareunia) Over 12 Weeks | The primary outcome is severity of the most bothersome vaginal symptom: dryness or dyspareunia. The Vaginal Symptom Measure (VSM) was used to evaluate the severity of vaginal dryness and dyspareunia. The VSM uses a 5- point ordinal response scale; 1=none, 2=mild, 3=moderate, 4=severe and 5=very severe to measure the severity associated with vaginal dryness and/or dyspareunia. For each patient, the change in severity was calculated by subtracting the baseline from the week 12 reported score. Therefore, the full range of scores ranges from -4 (greatest decrease in severity) to 4 (greatest increase in severity). A negative score indicates a decrease in severity from baseline, zero indicates no reported affect and positive scores indicate a more severe report at week 12. The primary assessment method will be a comparison of the averages of the changes over time in the severity items for the most bothersome symptom from baseline to 12 weeks (as indicated at baseline). | At baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vulvar cancer, depression, anxiety disorder, cognitive/functional effects, sexual dysfunction, cancer survivor, breast cancer, cervical cancer, fallopian tube cancer, uterine sarcoma, vaginal cancer, ovarian epithelial cancer, ovarian germ cell tumor, ovarian sarcoma, ovarian stromal cancer, primary peritoneal cavity cancer, endometrial cancer