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

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.

Inclusion Criteria:

1. Age ≥ 18 years

2. 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:

1. 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

2. 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

3. 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.

4. 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.

5. Vaginal symptoms must have been present ≥ 2 months prior to randomization.

6. Life expectancy > 12 months.

7. Ability to complete questionnaires by themselves or with assistance.

8. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.

9. The patient must provide informed written consent.

10. Willing to return to the enrolling institution for follow-up.

11. Willing to provide blood samples for correlative research purposes.

Exclusion Criteria:

1. 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.

2. Current diagnosis of an active vaginal infection, if symptoms of vaginal infection,
this must be ruled out (ie, foul discharge, fever).

3. Concurrent chemotherapy (long term adjuvant herceptin, lapatanib, and/or bevacizumab
is allowed.

4. 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.

5. 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.

6. 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.

7. Use of pharmacologic soy or phytoestrogen preparations (Dietary intake of soy - ie
milk is acceptable).

8. On a placebo controlled trial for endocrine therapy.

9. Prior or concurrent pelvic radiation therapy.

10. Prior radical pelvic surgery, specifically vaginectomy or pelvic exenteration
(TAH/BSO) is allowed).

11. Diagnosis of any of the following conditions within the past five years:

1. Essential vulvodynia

2. Vulvar vestibulitis

3. Bartholin cyst/abscess

4. History of Bartholin gland surgery

5. Lichen sclerosis

6. Lichen planus of the vulvovaginal region

7. Desquamative vaginitis

12. History or current diagnosis of any of the following conditions:

1. Vulvar or vaginal dysplasia

2. Vaginal prolapse

13. Women of childbearing potential, premenopausal women.