Vaginal Testosterone Cream vs ESTRING for Vaginal Dryness or Decreased Libido in Early Stage Breast Cancer Patients

Study Overview
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Brief Summary
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The purpose of this clinical research study is to determine whether the ESTRING or a special preparation of a testosterone cream inserted vaginally are safe for use in breast cancer patients. This study will also evaluate if either of these treatments can improve symptoms of vaginal dryness or decreased sexual interest that are related to your treatment for breast cancer.

Detailed Description
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There is a growing body of scientific literature to suggest that sexual functioning is one of the most distressing problems experienced by breast cancer survivors. Vaginal dryness, dyspareunia (pain during sexual intercourse), and decreased libido are common complaints among breast cancer patients. With increasing use of aromatase inhibitors which are associated with a higher rate of vaginal dryness than tamoxifen, these problems are becoming even more prominent. This study will evaluate the safety and tolerability of the ESTRING and 1% testosterone cream administered vaginally as treatments for vaginal dryness and/or decreased libido in women receiving an aromatase inhibitor for early stage breast cancer.

Official Title
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A Phase II Study of Vaginal Testosterone Cream vs. the ESTRING for Vaginal Dryness or Decreased Libido in Early Breast Cancer Patients Treated With Aromatase Inhibitors

Conditions
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Sexual Dysfunction, Physiological

Intervention / Treatment
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* Drug: Testosterone Cream
* Drug: Estring


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed Stage I-III breast cancer who are taking an aromatase inhibitor as adjuvant hormonal therapy. Patient must have started the aromatase inhibitor at least 60 days prior to enrolling. Postmenopausal estradiol levels at baseline as measured by standard laboratory analysis. Patient may be rendered postmenopausal through the use of a GnRH agonist, but must have confirmed post-menopausal levels of serum estradiol on two lab tests at least one month apart. If patient has been rendered post-menopausal by adjuvant chemotherapy but has had a period within the past 12 months, post-menopausal levels of serum estradiol must be documented on two lab tests at least 3 months apart. Age ≥18 and ≤80 years old. ECOG ≤1 Adequate hematologic, hepatic, and renal function as defined by: Hgb ≥9 g/dL Absolute neutrophil count (ANC)/absolute granulocyte count (AGC) ≥1500 cells/mm3 Platelet count ≥100,000/mm3 Serum creatinine ≤1.5 mg/dL Total bilirubin ≤1.5 times the ULN; and aspartate aminotransferase ≤3 times the ULN Normal thyroid function tested within the past 6 months (Patients with a diagnosis of hypothyroidism and on thyroid supplementation must have had thyroid function tests in the normal range within the past 3 months) Patient must have recovered from the side effects of previous chemotherapy, surgery, or radiation therapy for early breast cancer. Exclusion Criteria: History of radiation to the vaginal area Concurrent treatment with any type of oral, injectable or topical form of estrogen or androgen therapy including natural supplements marketed as hormone replacement products Initiation of topical moisturizers (for example, Replens), or herbal or alternative medicines to manage the symptoms of vaginal dryness while on study. Patients who were previously using these products may continue them with the same usage pattern while on study. Use of vaginal hormonal products (rings, inserts, creams, gels) containing estrogens or androgens within the past 30 days. History of an abnormal pap smear within the last 12 months History of endometrial or ovarian cancer Any episode of vaginal bleeding in the past 6 months that has not been evaluated by a gynecological exam and/or pelvic ultrasound History of sexual dysfunction prior to diagnosis of breast cancer ( Sexual dysfunction will be defined as loss of libido or inability to achieve orgasm for which patient sought medical attention or which patient felt significantly interfered with quality of life.) Moderate or severe depression for which the patient is receiving ongoing psychological counseling and/or taking antidepressants, and for whom, in the investigators opinion may be interfering in the patients sexual function independent of the side effects of breast cancer and aromatase inhibitor use. Use of any investigational agent for breast cancer within 3 weeks of study entry.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Testosterone Cream<br>Testosterone Cream 1% micronized in velvachol - 0.5 gm of cream vaginally each night for two weeks, then 3 times a week for total of 12 weeks of treatment | Drug: Testosterone Cream<br>* 1% micronized in velvachol - 0.5 gm of cream vaginally each night for two weeks, then 3 times a week for total of 12 weeks of treatment<br>* Other names: intravaginal testosterone cream;|
| Active Comparator: Estring<br>Estring 2mg ring inserted vaginally once every 12 weeks | Drug: Estring<br>* 2mg ring inserted vaginally once every 12 weeks<br>* Other names: ESTRING Estrodial Vaginal Ring;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Persistently Elevated Serum Estradiol Level Outside the Post-menopausal Range | Liquid chromatography tandem mass spectrometry (Quest Diagnostics). Persistently elevated serum estradiol level outside the post-menopausal range was defined as: Serum estradiol >10 pg/dl on two consecutive collections at least 4 weeks apart. 2. If baseline estradiol was >10 pg/dl, subsequent levels >10 pg/ml higher than baseline were considered a significant elevation outside the post-menopausal range. | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Estradiol (E2) | serial measurements of serum estradiol (E2) by liquid chromatography tandem mass spectrometry (Quest Diagnostics) | 12 weeks | 
| Matched E2 by Commercial and Research (RIA) Analyses | Serum estradiol assays sent to the UCSF clinical laboratory are sent out to Quest Diagnostics, which uses LC/MS for their ultra-sensitive estradiol assay. Samples were also sent to a specialized research lab in England which has developed an ultrasensitive assay using radioimmunoassay (RIA) after ether extraction (sensitivity limit of 3pmol/l) to quantify low levels of estradiol found in post-menopausal women | baseline, 4 weeks | 
| Total Testosterone Levels | By serum ultrasensitive total testosterone test (Quest Diagnostics) | 12 weeks | 
| Sexual Quality of Life | Cancer Rehabilitation Evaluation System (CARES) Sexual Dysfunction (SD) and Sexual Interest (SI) Subscales range from 0 to 4 and measure the severity of problems, with higher scores indicating more difficulty. | Baseline, Week 4, Week 12 | 
| Sexual Satisfaction | Participants were asked to respond to a Sexual Satisfaction One Item Measure which asked Overall, how satisfactory to you is your sexual relationship with your partner? Response options range from 1 (Extremely unsatisfactory) to 6 (Extremely satisfactory). | Baseline, Week 4, Week 12 | 
| Change in Vaginal Epithelium Scores | During a gynecologic exam, the vaginal epithelium was assessed by an examiner using the Vaginal Atrophy Scoring Scale to evaluate Rugae (lack of), Pallor (pinkness), Petechiae, Mucosal thinning, Dryness. Scores range from 0 (none) to 3 (severe); higher scores indicate less favorable outcomes. | Baseline, 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaginal Testosterone Cream, ESTRING