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

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 3

Conditions: Breast Cancer; Gynecologic Cancer

Treatments: Drug: prasterone; Other: placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01376349

NCI-2011-02677 (Registry Identifier)

NCCTG-N10C1

CDR0000702003 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 464 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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464 participants in 3 patient groups, including a placebo group

Arm I low dose DHEA

Experimental group

Description:

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.

Treatment:

Drug: prasterone

Arm II high dose DHEA

Experimental group

Description:

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.

Treatment:

Drug: prasterone

Arm III placebo

Placebo Comparator group

Description:

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.

Treatment:

Other: placebo