Vaginal DHEA for Vaginal Symptoms: A Phase III Randomized, Double Blind, Placebo- Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 464
- 试验地点
- 277
- 主要终点
- Alleviation of the Most Bothersome Vaginal Symptom (Vaginal Dryness or Dyspareunia) Over 12 Weeks
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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.
研究组 & 干预措施
Arm I low dose DHEA
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.
干预措施: prasterone (Drug)
Arm II high dose DHEA
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.
干预措施: prasterone (Drug)
Arm III placebo
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.
干预措施: placebo (Other)
结局指标
主要结局
Alleviation of the Most Bothersome Vaginal Symptom (Vaginal Dryness or Dyspareunia) Over 12 Weeks
时间窗: At baseline and 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).
次要结局
未报告次要终点