Vaginal Testosterone Cream For Atrophic Vaginitis in Women Taking Aromatase Inhibitors for Breast Cancer.
Primary Purpose
Vaginitis, Dyspareunia, Breast Neoplasms
Status
Suspended
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Testosterone propionate
Sponsored by
About this trial
This is an interventional treatment trial for Vaginitis focused on measuring Testosterone, Vaginal administration, Aromatase inhibitors
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed breast cancer (any stage).
- Currently be using an aromatase inhibitor (anastrazole, exemestane or letrozole) for primary or adjuvant breast cancer treatment.
- Must have complaints of vaginal itching, vaginal dryness and/or dyspareunia.
- Not undergoing active chemotherapeutic or radiotherapeutic treatment
- Age >18 years
- Life expectancy of greater than 2 months.
- CALGB (ZUBROD) performance status <3.
- Post-menopausal - defined by absence of menses for at least 12 months and/or an FSH >25. Not post-menopausal as a function of medications intended to suppress ovarian function, such as gonadotropin releasing hormone agonists. Surgically post-menopausal subject eligible.
- The effects of topical testosterone cream on the developing human fetus at the recommended therapeutic dose are unknown. For this study only post-menopausal women are included and all women of child-bearing potential are excluded. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Exclusion Criteria:
- Patients who have not recovered from adverse events due to chemotherapeutic agents administered more than 4 weeks earlier.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to testosterone or the emollient delivery cream used in the study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women and women who are breast-feeding are excluded from this study because it is limited to post-menopausal women.
Sites / Locations
- Memorial Hospital of Rhode Island,
- Fletcher Allen Health Care, University of Vermont
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Vaginal Testosterone
Arm Description
Daily application of vaginal testosterone for 28 days.
Outcomes
Primary Outcome Measures
Serum estradiol levels
Will evaluate if serum estradiol levels, measured with a high sensitivity assay, increase in women taking aromatase inhibitors for breast cancer after study intervention of 28 days of vaginal testosterone treatment.
Secondary Outcome Measures
Symptoms of vaginal atrophy
Will evaluate if symptoms of atrophic vaginitis measured on a symptoms questionnaire impove in women taking aromatase inhibitors for breast cancer after study intervention of 28 days of vaginal testosterone treatment.
Clinical signs of vaginal atrophy.
Will evaluate if clinical signs of vaginal atrophy on gynecologic examination decrease in women taking aromatase inhibitors for breast cancer after study intervention of 28 days of vaginal testosterone treatment.
pathologic measures of atrophic vaginitis
Will evaluate if pathologic measures of atrophic vaginitis including maturation index and vaginal pH change in women on aromatase inhibitos for breast cancer after study intervention of 28 days of vaginal testosterone treatment.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01122342
Brief Title
Vaginal Testosterone Cream For Atrophic Vaginitis in Women Taking Aromatase Inhibitors for Breast Cancer.
Official Title
Vaginal Testosterone Cream For Atrophic Vaginitis in Women Taking Aromatase Inhibitors for Breast Cancer.
Study Type
Interventional
2. Study Status
Record Verification Date
May 2010
Overall Recruitment Status
Suspended
Why Stopped
Evaluating outcomes of current subjects pre further enrollment/dose reduction.
Study Start Date
December 2006 (undefined)
Primary Completion Date
December 2010 (Anticipated)
Study Completion Date
January 2011 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
University of Vermont
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Atrophic vaginitis is a condition in which the skin lining of the vagina and labia becomes thin and symptoms develop including vaginal itching, vaginal discomfort and dyspareunia. These can significantly affect women's comfort, sexuality and quality of life.
Treatment for this condition includes estrogen given in pill form, commonly known as hormone replacement therapy and local estrogen treatments, such as vaginal estrogen creams and topical vaginal lubricants. Unfortunately, systemic estrogen is contraindicated in many women with breast cancer. Some providers also feel that women who are taking aromatase inhibitors for their breast cancer should also not use local estrogens as several small studies suggest that these treatments might effect estrogen levels and thus might change how effective the aromatase inhibitors are. If these women choose not to use any form of estrogen therapy there symptoms may not be well controlled with other treatments.
The investigators hypothesize that a vaginal testosterone cream might be a safe and effective alternative treatment for these women. This small study is intended to test the hypothesis that testosterone cream will not increase estrogen (estradiol) levels and that it will improve the symptoms of atrophic vaginitis including vaginal dryness, vaginal itching and pain with intercourse.
The investigators will enroll women in the trial who are taking an aromatase inhibitor and have the symptoms mentioned above. They will receive a testosterone cream which will be applied vaginally once a day for 28 days. If good results are found with a prespecified dose of testosterone, a lower dose will be tested in the next group of women enrolled.
Detailed Description
Atrophic vaginitis is a condition in which the skin lining of the vagina and labia becomes thin, usually due to a decreased estrogen state - such as menopause. Symptoms of atrophic vaginitis include vaginal itching, vaginal discomfort and dyspareunia and can significantly affect women's comfort, sexuality and quality of life.
Treatment for this condition includes estrogen given in pill form, commonly known as hormone replacement therapy and local estrogen treatments, such as vaginal estrogen creams and topical vaginal lubricants. Unfortunately, systemic estrogen is contraindicated in many women with breast cancer. Some providers also feel that women who are taking aromatase inhibitors for their breast cancer should also not use local estrogens as several small studies suggest that these treatments might effect estrogen levels and thus might change how effective the aromatase inhibitors are. If these women choose not to use any form of estrogen therapy there symptoms may not be well controlled with other treatments.
The investigators hypothesize that a vaginal testosterone cream might be a safe and effective alternative treatment for these women. This small study is intended to test the hypothesis that testosterone cream will not increase estrogen (estradiol) levels and that it will improve the symptoms of atrophic vaginitis including vaginal dryness, vaginal itching and pain with intercourse.
The investigators will enroll women in the trial who are taking an aromatase inhibitor and have the symptoms mentioned above. They will receive a testosterone cream which will be applied vaginally once a day for 28 days. If good results are found with a prespecified dose of testosterone, a lower dose will be tested in the next group of women enrolled.
Objectives:
PRIMARY OBJECTIVE:
1.1. Does topical testosterone cream affect serum estradiol levels in women taking aromatase inhibitors for breast cancer?
SECONDARY OBJECTIVES:
1.2. Can atrophic vaginitis and resultant symptoms of vaginal dryness, itching and dyspareunia in women taking aromatase inhibitors for the treatment of breast cancer be improved with a topical testosterone cream?
1.3. Does topical testosterone cream affect physical findings, pH and cytologic changes in atrophic vaginitis?
Schema:
Intervention - Subjects will apply a testosterone cream to the vaginal area daily for one month (28 days).
Evaluation - Before and after the study intervention participants will have testosterone and high-sensitivity estradiol tested. They will complete a questionnaire on symptoms of atrophic vaginitis and have a gynecologic examination (with visual, speculum, pH and sample of vaginal epithelial cells.)
Endpoints - Serum estradiol levels Improvement in symptoms of atrophic vaginitis, as measured by questionnaire. Atrophic vaginitis as measured by gynecological examination (including pH and cytology to assess maturation index).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vaginitis, Dyspareunia, Breast Neoplasms
Keywords
Testosterone, Vaginal administration, Aromatase inhibitors
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Vaginal Testosterone
Arm Type
Experimental
Arm Description
Daily application of vaginal testosterone for 28 days.
Intervention Type
Drug
Intervention Name(s)
Testosterone propionate
Other Intervention Name(s)
Testosterone cream,, topical testosterone,, vaginal testosterone
Intervention Description
Testosterone USP micronized powder at a dose of 1mg/gr will be made into a paste with polysorbate 80 NF liquid and will be placed in an emollient cream base. A calibrated applicator will be supplied to measure out doses containing 300mcg of testosterone for daily application. The cream will be applied daily for 28 days. As above if safety and efficacy endpoints are met at this dose a lower dose (150mcg) will be used and if in tun this meets safety and efficacy endpoints a lower dose (75mcg) will be used.
Primary Outcome Measure Information:
Title
Serum estradiol levels
Description
Will evaluate if serum estradiol levels, measured with a high sensitivity assay, increase in women taking aromatase inhibitors for breast cancer after study intervention of 28 days of vaginal testosterone treatment.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Symptoms of vaginal atrophy
Description
Will evaluate if symptoms of atrophic vaginitis measured on a symptoms questionnaire impove in women taking aromatase inhibitors for breast cancer after study intervention of 28 days of vaginal testosterone treatment.
Time Frame
28 days
Title
Clinical signs of vaginal atrophy.
Description
Will evaluate if clinical signs of vaginal atrophy on gynecologic examination decrease in women taking aromatase inhibitors for breast cancer after study intervention of 28 days of vaginal testosterone treatment.
Time Frame
28 days
Title
pathologic measures of atrophic vaginitis
Description
Will evaluate if pathologic measures of atrophic vaginitis including maturation index and vaginal pH change in women on aromatase inhibitos for breast cancer after study intervention of 28 days of vaginal testosterone treatment.
Time Frame
28 days
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed breast cancer (any stage).
Currently be using an aromatase inhibitor (anastrazole, exemestane or letrozole) for primary or adjuvant breast cancer treatment.
Must have complaints of vaginal itching, vaginal dryness and/or dyspareunia.
Not undergoing active chemotherapeutic or radiotherapeutic treatment
Age >18 years
Life expectancy of greater than 2 months.
CALGB (ZUBROD) performance status <3.
Post-menopausal - defined by absence of menses for at least 12 months and/or an FSH >25. Not post-menopausal as a function of medications intended to suppress ovarian function, such as gonadotropin releasing hormone agonists. Surgically post-menopausal subject eligible.
The effects of topical testosterone cream on the developing human fetus at the recommended therapeutic dose are unknown. For this study only post-menopausal women are included and all women of child-bearing potential are excluded. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Exclusion Criteria:
Patients who have not recovered from adverse events due to chemotherapeutic agents administered more than 4 weeks earlier.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to testosterone or the emollient delivery cream used in the study.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant women and women who are breast-feeding are excluded from this study because it is limited to post-menopausal women.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sabrina M Witherby, MD
Organizational Affiliation
Memorial Hospital of Rhode Island, Warren Alpert School od Medicine at Brown University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Hyman Muss, MD
Organizational Affiliation
University of North Carolina
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Marie Wood, MD
Organizational Affiliation
University of Vermont
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Hospital of Rhode Island,
City
Pawtucket
State/Province
Rhode Island
ZIP/Postal Code
02860
Country
United States
Facility Name
Fletcher Allen Health Care, University of Vermont
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States
12. IPD Sharing Statement
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Vaginal Testosterone Cream For Atrophic Vaginitis in Women Taking Aromatase Inhibitors for Breast Cancer.
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