Breast Cancer Female, Long-term Survivors, Postmenopausal Symptoms, Vaginal Atrophy
Conditions
Keywords
Postmenopausal, Breast Cancer Survivor, Vaginal
Brief summary
The purpose of this research is to gather information on the safety and effectiveness of Intrarosa®, also known as Dehydroepiandrosterone (DHEA), and prasterone. By doing this study, the investigators hope to learn if Intrarosa® can improve vaginal discomfort. Participants will be assigned to one of two groups. One group will use Intrarosa® once a day. The other group will use Replens™ two times a week.
Detailed description
This will be a two-armed, randomized Phase II trial. All study subjects will be asked to fill out a simple 5-question sexual functioning survey. If any concern about sexual functioning is noted, the subject will also be asked to fill out a more extensive Sexual functioning tool, to help determine which domain of sexual functioning is the most bothersome. Subjects who complete the initial screening will be randomly assigned to the Intrarosa® or Replens™ arm by a 1:1 ratio. Subjects randomized to the Intrarosa® arm will use 6.5 mg daily for 12 weeks (±1 week). Subjects randomized to the Replens™ arm will use a vaginal applicator two times per week for 12 weeks. At baseline and at 12 weeks, subjects will undergo a physical exam including clinical breast and gynecological exam. During gynecologic exams, the vaginal Potential of Hydrogen (pH) will be determined and a swab of vaginal epithelium sent for determination of the Vaginal Maturation Index (VMI) and Maturation Value (MV). These will be used as objective physiologic markers to determine the improvement in vaginal atrophy. The cytologist's reading specimens will be blinded. Additionally, all study subjects will be asked to fill out questionnaires at baseline and again in 12 weeks.
Interventions
This is a vaginally administered suppository steroid indicated for the treatment of moderate to severe dyspareunia, a frequent symptom of vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause.
COMBINATION_PRODUCTVaginal Polycarbophil Moisturizer
This is an FDA cleared, over-the-counter personal lubricant for vaginal application, intended to moisturize and lubricate, to enhance the ease and comfort of intimate sexual activity and supplement the body's natural lubrication. It is non-sterile, water-based, non-irritating, non-greasy, non-staining vaginal gel delivered as a long-lasting moisturizer for vaginal dryness.
Sponsors
AMAG Pharmaceuticals, Inc.
University of Arkansas
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
SINGLE (Outcomes Assessor)
Masking description
The cytologist's reading specimens will be blinded.
Intervention model description
Subjects are randomly assigned to the Intrarosa® or Replens™ arm by a 1:1 ratio. Subjects randomized to the Intrarosa® arm will use 6.5 mg daily for 12 weeks (±1 week). Subjects randomized to the Replens™ arm will use a vaginal applicator two times per week for 12 weeks.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Postmenopausal patients with a history of breast cancer who have completed primary treatment with curative intent, who have been on an aromatase inhibitors (AI) for at least 6 months * Stage I-III, hormone receptor positive breast cancer regardless of human epidermal growth factor receptor 2 (HER2) status * Postmenopause defined as 12 months of spontaneous amenorrhea, or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels \> 40 mIU/mL (milli-international units per milliliter), or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy. FSH level will be documented on all subjects. * Patients reporting any symptoms of vaginal dryness or dyspareunia as assessed by the Brief Sexual Symptom Checklist for Women (BSSC-W) or the Female Sexual Function Index (FSFI) * No evidence of active malignant breast or gynecologic disease * Absence of undiagnosed, persistent or recurring genital bleeding that has not been evaluated to determine the cause \[6\] * No planned changes in AI during the study period * Mammogram (if appropriate, as determined by the treating physician and will be documented) within 12 months of study entry * Patients with documented normal Pap within 12 months of study entry
Exclusion criteria
* Use of any estrogen or progesterone depot-preparation drug or progestin implant in the last 6 months before study entry * Use of any androgen or anabolic steroids in the last 6 months before study entry * Use of any oral or transdermal hormonal products (estrogen, progestin, or DHEA) within the last 8 weeks prior to study entry; however, a subject can elect to wait for an 8-week washout period before study entry. * Use of any vaginal or intrauterine hormonal products in the last 8 weeks; however, a subject can elect to wait for an 8-week washout before study entry. * Use of any natural over the counter estrogenic products in the last 6 months; however, a subject can elect to wait for a 6-month washout before study entry. * Concomitant vulvar and vaginal surgical or laser treatments * Vaginal infection or confounding vulvar or active vaginal disease process * Prior radiation to the pelvis or history of gynecologic cancer * Inability to tolerate a vaginal/speculum exam * Undiagnosed, persistent or recurring genital bleeding or other indication of active pelvic disease process that has not been evaluated \[6\] * Clinically significant uncontrolled depression or severe psychiatric symptoms * If subject has an established routine of inert vaginal lubricant use for routine or occasional relief of vulvar or vaginal symptoms prior to the study period, it may be continued during the study period along with the study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Vaginal Maturation Index (VMI) Response From Baseline to Week 12 | Baseline and 12 weeks (±1 week) | The change in the subject's calculated VMI from baseline to the end of treatment at 12 weeks (±1 week). VMI = 1.0 x %S + 0.5 x %I + 0.0 x %P cells, which is the same as VMI = %S + (0.5 x %I) when simplified. It has a potential range of 0-100. A VMI of 65-100 suggests a normal premenopausal environment, 50-64 indicates a moderate estrogenic effect, and \< 50 indicates atrophy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Dyspareunia Scores on the Brief Sexual Symptom Checklist for Women (BSSC-W) From Baseline to Week 12 | 12 weeks (±1 week) | The Dyspareunia Score on the BSSC-W asks if there is a problem with pain during sex. A difference score of 0 indicated no change in whether it was a problem. The min and max are both 0 which makes the range also 0. Only 2 participants had week 12 scores. These scores were both 1. (So the min and max were 1 with the range being 0.) Of the baseline scores, these 2 participants both had scores of 1 again. (So the min and max for these 2 participants were both 1 with a range of 0.) If we include these 2 participants with the other 6 who have baseline dyspareunia scores on the BSSC-W, then 7 participants has a score of 1 and 1 participant had a score of 0. This would make the min, max, and range 0, 1, and 1 respectively. As for which value represents a better or worse outcome, 1 indicates presence of dyspareunia while 0 indicates absence of dyspareunia, so 1 is a worse outcome than 0. Subscales are not combined here to produce a total score. |
| Difference in Vaginal Dryness Scores on the Brief Sexual Symptom Checklist for Women (BSSC-W) From Baseline to Week 12 | 12 weeks (±1 week) | The min and the max are both 0 which make the range also 0. These were obtained from subtracting each participant's score at baseline from their score at week 12. Only 2 participants had week 12 scores. These scores were both 1. Of the baseline scores, these 2 participants both had scores of 1 again. If 2 participants with the other 6 have baseline dyspareunia scores on the BSSC-W, then 7 participants have a score of 1 and 1 participant had a score of 0. This would make the min, max, and range 0, 1, and 1 respectively. As for which value represents a better or worse outcome, 1 indicates presence of vaginal dryness (problem with decreased vaginal lubrication) while 0 indicates absence of vaginal dryness (or an absence of this problem of decreased vaginal lubrication), so 1 is a worse outcome than 0. Subscales are not combined here to produce a total score. |
| Difference in Vaginal pH From Baseline to Week 12 | 12 weeks (±1 week) | Vaginal pH was used as an objective physiologic marker to determine the improvement in vaginal atrophy. pH is a measure of acidity and alkalinity and can range from 0 to 14, with 7 being neutral. Lower pH scores are acidic and higher pH scores are basic or alkaline. A normal healthy vaginal pH is 4.5. As the vaginal epithelium becomes thinner and more atrophic, the mucosa has less glycogen content and less lactobacilli to convert the glycogen into lactic acid, which results in an increase in the vaginal pH. |
| Difference in Vaginal Dryness Subscale Scores on the Female Sexual Dysfunction Index (FSFI) From Baseline to Week 12 | 12 weeks (±1 week) | The Vaginal Dryness (or Lubrication) Subscale Score on the Female Sexual Dysfunction Index ranges from 0-5 with higher scores indicating better sexual function, so more lubrication. |
| Difference in Quality of Life on the Quality of Life - Cancer Survivor Version (QOL-CSV) From Baseline to Week 12 | 12 weeks (±1 week) | The Quality of Life - Cancer Survivor Version ranges from 0-10 with higher scores indicating a higher quality of life. T here are only 2 difference scores for each of the 4 subscales. The min, max, and ranges of these Well-Being Subscales: Physical -1.00, -0.62, and 0.38. Psychological -0.72, 0.94, and 1.67. Social 0.75, 1.25, and 0.50. Spiritual -1.57, 3.29, and 4.86. For Psychological the min, max, and range are 2.61, 6.83, and 4.22. For Social the min, max, and range are 2.63, 7.38, and 4.75. For Spiritual the min, max, and range are 4.43, 8.43, and 4.00. A negative difference score indicates a worsening of quality of life while a positive score indicates that qualify of life got better. Subscales were not combined here to produce a total score. For the baseline and week 12 scores on the QOL-CSV, higher scores mean higher quality of life. |
| Difference in Dyspareunia Subscale Scores on the Female Sexual Dysfunction Index (FSFI) From Baseline to Week 12 | 12 weeks (±1 week) | The Dyspareunia Subscale Score on the Female Sexual Dysfunction Index ranges from 0-5 with higher scores indicating better sexual function, so less dyspareunia. |
Countries
United States
Participant flow
Recruitment details
Potential subjects will be identified in the UAMS CI and UAMS Women's Health clinics and from the CARTI Cancer Center, during routine clinic appointments by the provider or research staff. Potential research subjects may also contact the UAMS Cancer Institute's Clinical Trials Office regarding participation based on the information found within the IRB-approved DHEA flyer that is to be distributed amongst UAMS and the CARTI medical clinics.
Pre-assignment details
Females of childbearing age and potential must have negative pregnancy test at screening. Any consented individuals who do not indicate sexual complaints on Question 1 of the BSSC-W at baseline will be considered a screen fail and will not complete the FSFI or continue in the study.
Participants by arm
| Arm | Count |
|---|---|
| Intrarosa & Standard of Care Aromatase Inhibitor Subjects randomized to the Intrarosa® arm will use 6.5 mg daily for 12 weeks (±1 week). | 5 |
| Replens & Standard of Care Aromatase Inhibitor Subjects randomized to the Replens™ arm will use a vaginal applicator two times per week for 12 weeks (±1 week). | 3 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Ineligible | 0 | 1 |
| Overall Study | Noncompliance | 2 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Intrarosa & Standard of Care Aromatase Inhibitor | Replens & Standard of Care Aromatase Inhibitor | Total |
|---|---|---|---|
| Age, Continuous | 57.8 years STANDARD_DEVIATION 3.96 | 54.00 years STANDARD_DEVIATION 15.39 | 56.38 years STANDARD_DEVIATION 8.98 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 2 Participants | 6 Participants |
| Region of Enrollment United States | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Vaginal Maturation Index (VMI) | 50.83 Units on a scale STANDARD_DEVIATION 16.65 | 36.67 Units on a scale STANDARD_DEVIATION 23.23 | 43.75 Units on a scale STANDARD_DEVIATION 19.67 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 3 |
| other Total, other adverse events | 4 / 5 | 1 / 3 |
| serious Total, serious adverse events | 0 / 5 | 0 / 3 |
Outcome results
Primary
Difference in Vaginal Maturation Index (VMI) Response From Baseline to Week 12
The change in the subject's calculated VMI from baseline to the end of treatment at 12 weeks (±1 week). VMI = 1.0 x %S + 0.5 x %I + 0.0 x %P cells, which is the same as VMI = %S + (0.5 x %I) when simplified. It has a potential range of 0-100. A VMI of 65-100 suggests a normal premenopausal environment, 50-64 indicates a moderate estrogenic effect, and \< 50 indicates atrophy.
Time frame: Baseline and 12 weeks (±1 week)
Population: Out of 8 participants assigned to a treatment arm, only 2 had VMI measured at both the baseline and 12-week visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intrarosa & Standard of Care Aromatase Inhibitor | Difference in Vaginal Maturation Index (VMI) Response From Baseline to Week 12 | -7.5 Units on a scale | Standard Deviation 24.75 |
Secondary
Difference in Dyspareunia Scores on the Brief Sexual Symptom Checklist for Women (BSSC-W) From Baseline to Week 12
The Dyspareunia Score on the BSSC-W asks if there is a problem with pain during sex. A difference score of 0 indicated no change in whether it was a problem. The min and max are both 0 which makes the range also 0. Only 2 participants had week 12 scores. These scores were both 1. (So the min and max were 1 with the range being 0.) Of the baseline scores, these 2 participants both had scores of 1 again. (So the min and max for these 2 participants were both 1 with a range of 0.) If we include these 2 participants with the other 6 who have baseline dyspareunia scores on the BSSC-W, then 7 participants has a score of 1 and 1 participant had a score of 0. This would make the min, max, and range 0, 1, and 1 respectively. As for which value represents a better or worse outcome, 1 indicates presence of dyspareunia while 0 indicates absence of dyspareunia, so 1 is a worse outcome than 0. Subscales are not combined here to produce a total score.
Time frame: 12 weeks (±1 week)
Population: Out of 8 participants assigned to a treatment arm, only 2 took the BSSC-W at both the baseline and 12-week visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intrarosa & Standard of Care Aromatase Inhibitor | Difference in Dyspareunia Scores on the Brief Sexual Symptom Checklist for Women (BSSC-W) From Baseline to Week 12 | 0.00 Units on a scale | Standard Deviation 0 |
Secondary
Difference in Dyspareunia Subscale Scores on the Female Sexual Dysfunction Index (FSFI) From Baseline to Week 12
The Dyspareunia Subscale Score on the Female Sexual Dysfunction Index ranges from 0-5 with higher scores indicating better sexual function, so less dyspareunia.
Time frame: 12 weeks (±1 week)
Population: Out of 8 participants assigned to a treatment arm, only 2 took the FSFI at both the baseline and 12-week visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intrarosa & Standard of Care Aromatase Inhibitor | Difference in Dyspareunia Subscale Scores on the Female Sexual Dysfunction Index (FSFI) From Baseline to Week 12 | 2.20 Units on a scale | Standard Deviation 3.11 |
Secondary
Difference in Quality of Life on the Quality of Life - Cancer Survivor Version (QOL-CSV) From Baseline to Week 12
The Quality of Life - Cancer Survivor Version ranges from 0-10 with higher scores indicating a higher quality of life. T here are only 2 difference scores for each of the 4 subscales. The min, max, and ranges of these Well-Being Subscales: Physical -1.00, -0.62, and 0.38. Psychological -0.72, 0.94, and 1.67. Social 0.75, 1.25, and 0.50. Spiritual -1.57, 3.29, and 4.86. For Psychological the min, max, and range are 2.61, 6.83, and 4.22. For Social the min, max, and range are 2.63, 7.38, and 4.75. For Spiritual the min, max, and range are 4.43, 8.43, and 4.00. A negative difference score indicates a worsening of quality of life while a positive score indicates that qualify of life got better. Subscales were not combined here to produce a total score. For the baseline and week 12 scores on the QOL-CSV, higher scores mean higher quality of life.
Time frame: 12 weeks (±1 week)
Population: Out of 8 participants assigned to a treatment arm, only 2 took the QOL-CSV at both the baseline and 12-week visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intrarosa & Standard of Care Aromatase Inhibitor | Difference in Quality of Life on the Quality of Life - Cancer Survivor Version (QOL-CSV) From Baseline to Week 12 | QOL-CSV Physical Well-Being Subscale | -0.81 Units on a scale | Standard Deviation 0.27 |
| Intrarosa & Standard of Care Aromatase Inhibitor | Difference in Quality of Life on the Quality of Life - Cancer Survivor Version (QOL-CSV) From Baseline to Week 12 | QOL-CSV Psychological Well-Being Subscale | 0.11 Units on a scale | Standard Deviation 1.18 |
| Intrarosa & Standard of Care Aromatase Inhibitor | Difference in Quality of Life on the Quality of Life - Cancer Survivor Version (QOL-CSV) From Baseline to Week 12 | QOL-CSV Social Well-Being Subscale | 1.00 Units on a scale | Standard Deviation 0.35 |
| Intrarosa & Standard of Care Aromatase Inhibitor | Difference in Quality of Life on the Quality of Life - Cancer Survivor Version (QOL-CSV) From Baseline to Week 12 | QOL-CSV Spiritual Well-Being Subscale | 0.86 Units on a scale | Standard Deviation 3.43 |
Secondary
Difference in Vaginal Dryness Scores on the Brief Sexual Symptom Checklist for Women (BSSC-W) From Baseline to Week 12
The min and the max are both 0 which make the range also 0. These were obtained from subtracting each participant's score at baseline from their score at week 12. Only 2 participants had week 12 scores. These scores were both 1. Of the baseline scores, these 2 participants both had scores of 1 again. If 2 participants with the other 6 have baseline dyspareunia scores on the BSSC-W, then 7 participants have a score of 1 and 1 participant had a score of 0. This would make the min, max, and range 0, 1, and 1 respectively. As for which value represents a better or worse outcome, 1 indicates presence of vaginal dryness (problem with decreased vaginal lubrication) while 0 indicates absence of vaginal dryness (or an absence of this problem of decreased vaginal lubrication), so 1 is a worse outcome than 0. Subscales are not combined here to produce a total score.
Time frame: 12 weeks (±1 week)
Population: Out of 8 participants assigned to a treatment arm, only 2 took the BSSC-W at both the baseline and 12-week visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intrarosa & Standard of Care Aromatase Inhibitor | Difference in Vaginal Dryness Scores on the Brief Sexual Symptom Checklist for Women (BSSC-W) From Baseline to Week 12 | 0.00 Units on a scale | Standard Deviation 0 |
Secondary
Difference in Vaginal Dryness Subscale Scores on the Female Sexual Dysfunction Index (FSFI) From Baseline to Week 12
The Vaginal Dryness (or Lubrication) Subscale Score on the Female Sexual Dysfunction Index ranges from 0-5 with higher scores indicating better sexual function, so more lubrication.
Time frame: 12 weeks (±1 week)
Population: Out of 8 participants assigned to a treatment arm, only 2 took the FSFI at both the baseline and 12-week visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intrarosa & Standard of Care Aromatase Inhibitor | Difference in Vaginal Dryness Subscale Scores on the Female Sexual Dysfunction Index (FSFI) From Baseline to Week 12 | 1.80 Units on a scale | Standard Deviation 2.55 |
Secondary
Difference in Vaginal pH From Baseline to Week 12
Vaginal pH was used as an objective physiologic marker to determine the improvement in vaginal atrophy. pH is a measure of acidity and alkalinity and can range from 0 to 14, with 7 being neutral. Lower pH scores are acidic and higher pH scores are basic or alkaline. A normal healthy vaginal pH is 4.5. As the vaginal epithelium becomes thinner and more atrophic, the mucosa has less glycogen content and less lactobacilli to convert the glycogen into lactic acid, which results in an increase in the vaginal pH.
Time frame: 12 weeks (±1 week)
Population: Out of 8 participants assigned to a treatment arm, only 2 had vaginal pH measured at both the baseline and 12-week visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intrarosa & Standard of Care Aromatase Inhibitor | Difference in Vaginal pH From Baseline to Week 12 | -1.00 Units on a scale | Standard Deviation 2.83 |