Atrophic Vaginitis, Breast Cancer
Conditions
Keywords
vaginitis, Postmenopausal, 17-β estradiol, 09-110
Brief summary
The purpose of this study is to see if Vagifem® 10mcg is safe for women who have had breast cancer. Vagifem is an estrogen product. It is a tiny tablet that is inserted into the vagina. It relieves vaginal dryness. Women who have had breast cancer are usually told not to take estrogen. This is because estrogen use can lead to a breast cancer recurrence or a new primary breast cancer. It is unclear if the estrogen in Vagifem is only absorbed in the vagina. It may be absorbed into the blood stream for a short time and may cause a brief rise in your estrogen level. However, there is no clear evidence that this would cause any bad effects in patients with breast cancer. How much, if any, of these topical estrogens are absorbed through the vagina is not known. We also do not know what the impact is of low dose estrogen absorption on breast cancer outcomes. Also, the absorption should decrease as the mucus membranes are restored after estrogen exposure.
Interventions
DRUGVagifem® (vaginal 17β-estradiol) questionnaire & menopause symptom checklist
The goal is to have 30 patients on letrozole and 30 on anastrozole who are initiated on vaginal estrogen for symptoms of urogenital atrophy. All subjects will receive 10mcg vaginal 17-β estradiol tablets. Each subject will serve as her own control. We will monitor serum estradiol and follicle stimulating hormone (FSH) levels closely from 0-24 weeks. We will measure serum estradiol and FSH levels at baseline, and subsequently at weeks 2, 7, 12, 18 and 24 after commencing therapy with 10mcg vaginal 17-β estradiol.
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* History of breast cancer, stages I-III with pathology confirmed at MSKCC * Women who have completed all of their primary treatment (surgery, radiation therapy, adjuvant chemotherapy) with the exception of endocrine therapy and currently have no clinical evidence of disease. * Women who are currently on aromatase inhibitors for at least three months--either letrozole or anastrozole * Women with symptomatic urogenital atrophy: vaginal dryness, irritation, pruritus, dyspareunia, urinary frequency and/or urinary incontinence * Menopausal at study entry defined as: * Bilateral salpingo-oophorectomy independent of age * If natural menopause, age ≥ 50 with cessation of menses for at least 12 months * If menopause induced by chemotherapy, age ≥ 50 with no menstrual period at least 12 months after chemotherapy finished * At least 18 years of age * Able to participate in the informed consent process * Gynecology examination within six months * Able to read/speak English
Exclusion criteria
* Inability to give informed consent * Vaginal bleeding of unknown etiology within 12 months of study entry * History of prior vaginal 17-β estradiol or other topical estrogen use within the past six months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Estradiol From Baseline to Week 12 | 12 weeks | To determine the change in estradiol and follicle stimulating hormone (FSH) from baseline to twelve weeks in postmenopausal women receiving adjuvant aromatase inhibitors during treatment with low dose vaginal 10 µg 17- β estradiol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Estradiol Baseline to Week 24 | 24 weeks | To describe patterns of estradiol over the twenty-four week study period. |
| Change in FSH Levels Baseline to Week 24 | 24 weeks | To describe patterns of FSH levels over the twenty-four week study period. |
| To Compare the Rise in Estradiol in Women on Letrozole vs. Anastrozole During Treatment With Low Dose Vaginal 10 µg 17- β Estradiol to See if There Are Differences Between Aromatase Inhibitors. | 12 weeks | — |
| To Compare the Patient's Female Sexual Function Index (FSFI) Scores and Menopause Quality of Life Questionnaire at Baseline, Week 12 | Week 12 | The FSFI measures six domains of sexual function: desire, arousal, lubrication, orgasm, satisfaction and pain. An increase in FSFI score means better sexual function. The individual domain scores and full scale score of the FSFI are derived by the computational formula outlined in the table below. Individual domain scores are obtained by adding the scores of the individual items that comprise the domain and multiplying the sum by the domain factor (see below). The full scale score is obtained by adding the six domain scores. It should be noted that within the individual domains, a domain score of zero indicates that no sexual activity was reported during the past month. Domain Questions Score range Factor Minimum score Maximum score Desire 1, 2 1-5 0.6 1.2 6.0 Arousal 3, 4, 5, 6 0-5 0.3 0 6.0 Lubrication 7, 8, 9, 10 0-5 0.3 0 6.0 Orgasm 11, 12, 13 0-5 0.4 0 6.0 Satisfaction 14, 15, 16 0 (or 1)-5 0.4 0 6.0 Pain 17, 18, 19 0-5 0.4 0 6.0 Full Scale Score Range 2.0 36.0 |
| To Compare the Patient's Female Sexual Function Index (FSFI) Scores and Menopause Quality of Life Questionnaire at Baseline, Week 24 | Week 24 | The FSFI measures six domains of sexual function: desire, arousal, lubrication, orgasm, satisfaction and pain. The individual domain scores and full scale score of the FSFI are derived by the computational formula outlined in the table below. Individual domain scores are obtained by adding the scores of the individual items that comprise the domain and multiplying the sum by the domain factor (see below). The full scale score is obtained by adding the six domain scores. It should be noted that within the individual domains, a domain score of zero indicates that no sexual activity was reported during the past month. Domain Questions Score range Factor Minimum score Maximum score Desire 1, 2 1-5 0.6 1.2 6.0 Arousal 3, 4, 5, 6 0-5 0.3 0 6.0 Lubrication 7, 8, 9, 10 0-5 0.3 0 6.0 Orgasm 11, 12, 13 0-5 0.4 0 6.0 Satisfaction 14, 15, 16 0 (or 1)-5 0.4 0 6.0 Pain 17, 18, 19 0-5 0.4 0 6.0 Full Scale Score Range 2.0 36.0 |
| To Compare the Patient's Female Sexual Function Index (FSFI) Scores and Menopause Quality of Life Questionnaire at Baseline | Baseline | The FSFI measures six domains of sexual function: desire, arousal, lubrication, orgasm, satisfaction and pain. An increase in FSFI score means better sexual function. The individual domain scores and full scale score of the FSFI are derived by the computational formula outlined in the table below. Individual domain scores are obtained by adding the scores of the individual items that comprise the domain and multiplying the sum by the domain factor (see below). The full scale score is obtained by adding the six domain scores. It should be noted that within the individual domains, a domain score of zero indicates that no sexual activity was reported during the past month. Domain Questions Score range Factor Minimum score Maximum score Desire 1, 2 1-5 0.6 1.2 6.0 Arousal 3, 4, 5, 6 0-5 0.3 0 6.0 Lubrication 7, 8, 9, 10 0-5 0.3 0 6.0 Orgasm 11, 12, 13 0-5 0.4 0 6.0 Satisfaction 14, 15, 16 0 (or 1)-5 0.4 0 6.0 Pain 17, 18, 19 0-5 0.4 0 6.0 Full Scale Score Range 2.0 36.0 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Letrozole This is a prospective longitudinal pilot study, and the targeted patient population is postmenopausal women with breast cancer being treated with adjuvant aromatase inhibitors who are initiated on vaginal 17β-estradiol to relieve symptoms of atrophic vaginitis. | 12 |
| Anastrozole This is a prospective longitudinal pilot study, and the targeted patient population is postmenopausal women with breast cancer being treated with adjuvant aromatase inhibitors who are initiated on vaginal 17β-estradiol to relieve symptoms of atrophic vaginitis. | 19 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Pts did not start treatment | 2 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Letrozole | Total | Anastrozole |
|---|---|---|---|
| Age, Continuous | 55 years | 55 years | 56 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 26 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 30 Participants | 18 Participants |
| Region of Enrollment United States | 12 Participants | 31 Participants | 19 Participants |
| Sex: Female, Male Female | 12 Participants | 31 Participants | 19 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 19 |
| other Total, other adverse events | 0 / 12 | 0 / 19 |
| serious Total, serious adverse events | 0 / 12 | 0 / 19 |
Outcome results
Primary
Change in Serum Estradiol From Baseline to Week 12
To determine the change in estradiol and follicle stimulating hormone (FSH) from baseline to twelve weeks in postmenopausal women receiving adjuvant aromatase inhibitors during treatment with low dose vaginal 10 µg 17- β estradiol.
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Letrozole | Change in Serum Estradiol From Baseline to Week 12 | Baseline follicle stimulating hormone (FSH) | 70.92 pg/ml |
| Letrozole | Change in Serum Estradiol From Baseline to Week 12 | Baseline estradiol | 5.21 pg/ml |
| Letrozole | Change in Serum Estradiol From Baseline to Week 12 | Week 12 follicle stimulating hormone (FSH) | 71.67 pg/ml |
| Letrozole | Change in Serum Estradiol From Baseline to Week 12 | Week 12 estradiol | 5.23 pg/ml |
| Anastrozole | Change in Serum Estradiol From Baseline to Week 12 | Week 12 follicle stimulating hormone (FSH) | 63.28 pg/ml |
| Anastrozole | Change in Serum Estradiol From Baseline to Week 12 | Baseline estradiol | 4.46 pg/ml |
| Anastrozole | Change in Serum Estradiol From Baseline to Week 12 | Baseline follicle stimulating hormone (FSH) | 68.29 pg/ml |
| Anastrozole | Change in Serum Estradiol From Baseline to Week 12 | Week 12 estradiol | 6.72 pg/ml |
Secondary
Change in FSH Levels Baseline to Week 24
To describe patterns of FSH levels over the twenty-four week study period.
Time frame: 24 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Letrozole | Change in FSH Levels Baseline to Week 24 | Baseline FSH | 70.93 mIU/ml |
| Letrozole | Change in FSH Levels Baseline to Week 24 | Week 24 FSH | 74.07 mIU/ml |
| Anastrozole | Change in FSH Levels Baseline to Week 24 | Baseline FSH | 9.26 mIU/ml |
| Anastrozole | Change in FSH Levels Baseline to Week 24 | Week 24 FSH | 70.51 mIU/ml |
Secondary
Change in Serum Estradiol Baseline to Week 24
To describe patterns of estradiol over the twenty-four week study period.
Time frame: 24 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Letrozole | Change in Serum Estradiol Baseline to Week 24 | Baseline Estradiol | 5.21 pg/ mL |
| Letrozole | Change in Serum Estradiol Baseline to Week 24 | Week 24 Estradiol | 7.55 pg/ mL |
| Anastrozole | Change in Serum Estradiol Baseline to Week 24 | Baseline Estradiol | 4.46 pg/ mL |
| Anastrozole | Change in Serum Estradiol Baseline to Week 24 | Week 24 Estradiol | 9.26 pg/ mL |
Secondary
To Compare the Patient's Female Sexual Function Index (FSFI) Scores and Menopause Quality of Life Questionnaire at Baseline
The FSFI measures six domains of sexual function: desire, arousal, lubrication, orgasm, satisfaction and pain. An increase in FSFI score means better sexual function. The individual domain scores and full scale score of the FSFI are derived by the computational formula outlined in the table below. Individual domain scores are obtained by adding the scores of the individual items that comprise the domain and multiplying the sum by the domain factor (see below). The full scale score is obtained by adding the six domain scores. It should be noted that within the individual domains, a domain score of zero indicates that no sexual activity was reported during the past month. Domain Questions Score range Factor Minimum score Maximum score Desire 1, 2 1-5 0.6 1.2 6.0 Arousal 3, 4, 5, 6 0-5 0.3 0 6.0 Lubrication 7, 8, 9, 10 0-5 0.3 0 6.0 Orgasm 11, 12, 13 0-5 0.4 0 6.0 Satisfaction 14, 15, 16 0 (or 1)-5 0.4 0 6.0 Pain 17, 18, 19 0-5 0.4 0 6.0 Full Scale Score Range 2.0 36.0
Time frame: Baseline
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Letrozole | To Compare the Patient's Female Sexual Function Index (FSFI) Scores and Menopause Quality of Life Questionnaire at Baseline | 14.61 units on a scale |
| Anastrozole | To Compare the Patient's Female Sexual Function Index (FSFI) Scores and Menopause Quality of Life Questionnaire at Baseline | 16.01 units on a scale |
Secondary
To Compare the Patient's Female Sexual Function Index (FSFI) Scores and Menopause Quality of Life Questionnaire at Baseline, Week 12
The FSFI measures six domains of sexual function: desire, arousal, lubrication, orgasm, satisfaction and pain. An increase in FSFI score means better sexual function. The individual domain scores and full scale score of the FSFI are derived by the computational formula outlined in the table below. Individual domain scores are obtained by adding the scores of the individual items that comprise the domain and multiplying the sum by the domain factor (see below). The full scale score is obtained by adding the six domain scores. It should be noted that within the individual domains, a domain score of zero indicates that no sexual activity was reported during the past month. Domain Questions Score range Factor Minimum score Maximum score Desire 1, 2 1-5 0.6 1.2 6.0 Arousal 3, 4, 5, 6 0-5 0.3 0 6.0 Lubrication 7, 8, 9, 10 0-5 0.3 0 6.0 Orgasm 11, 12, 13 0-5 0.4 0 6.0 Satisfaction 14, 15, 16 0 (or 1)-5 0.4 0 6.0 Pain 17, 18, 19 0-5 0.4 0 6.0 Full Scale Score Range 2.0 36.0
Time frame: Week 12
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Letrozole | To Compare the Patient's Female Sexual Function Index (FSFI) Scores and Menopause Quality of Life Questionnaire at Baseline, Week 12 | 17.75 units on a scale |
| Anastrozole | To Compare the Patient's Female Sexual Function Index (FSFI) Scores and Menopause Quality of Life Questionnaire at Baseline, Week 12 | 18.87 units on a scale |
Secondary
To Compare the Patient's Female Sexual Function Index (FSFI) Scores and Menopause Quality of Life Questionnaire at Baseline, Week 24
The FSFI measures six domains of sexual function: desire, arousal, lubrication, orgasm, satisfaction and pain. The individual domain scores and full scale score of the FSFI are derived by the computational formula outlined in the table below. Individual domain scores are obtained by adding the scores of the individual items that comprise the domain and multiplying the sum by the domain factor (see below). The full scale score is obtained by adding the six domain scores. It should be noted that within the individual domains, a domain score of zero indicates that no sexual activity was reported during the past month. Domain Questions Score range Factor Minimum score Maximum score Desire 1, 2 1-5 0.6 1.2 6.0 Arousal 3, 4, 5, 6 0-5 0.3 0 6.0 Lubrication 7, 8, 9, 10 0-5 0.3 0 6.0 Orgasm 11, 12, 13 0-5 0.4 0 6.0 Satisfaction 14, 15, 16 0 (or 1)-5 0.4 0 6.0 Pain 17, 18, 19 0-5 0.4 0 6.0 Full Scale Score Range 2.0 36.0
Time frame: Week 24
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Letrozole | To Compare the Patient's Female Sexual Function Index (FSFI) Scores and Menopause Quality of Life Questionnaire at Baseline, Week 24 | 18.32 units on a scale |
| Anastrozole | To Compare the Patient's Female Sexual Function Index (FSFI) Scores and Menopause Quality of Life Questionnaire at Baseline, Week 24 | 21.09 units on a scale |
Secondary
To Compare the Rise in Estradiol in Women on Letrozole vs. Anastrozole During Treatment With Low Dose Vaginal 10 µg 17- β Estradiol to See if There Are Differences Between Aromatase Inhibitors.
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Letrozole | To Compare the Rise in Estradiol in Women on Letrozole vs. Anastrozole During Treatment With Low Dose Vaginal 10 µg 17- β Estradiol to See if There Are Differences Between Aromatase Inhibitors. | Baseline Estradiol | 5.21 pg/ml |
| Letrozole | To Compare the Rise in Estradiol in Women on Letrozole vs. Anastrozole During Treatment With Low Dose Vaginal 10 µg 17- β Estradiol to See if There Are Differences Between Aromatase Inhibitors. | Week 12 Estradiol | 5.23 pg/ml |
| Anastrozole | To Compare the Rise in Estradiol in Women on Letrozole vs. Anastrozole During Treatment With Low Dose Vaginal 10 µg 17- β Estradiol to See if There Are Differences Between Aromatase Inhibitors. | Baseline Estradiol | 4.46 pg/ml |
| Anastrozole | To Compare the Rise in Estradiol in Women on Letrozole vs. Anastrozole During Treatment With Low Dose Vaginal 10 µg 17- β Estradiol to See if There Are Differences Between Aromatase Inhibitors. | Week 12 Estradiol | 6.72 pg/ml |