Clinical trial NCT00698035: Vaginal Testosterone Cream vs ESTRING for Vaginal Dryness or Decreased Libido in Early Stage Breast Cancer Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sexual Dysfunction, Physiological
Keywords: Vaginal Testosterone Cream
ESTRING
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2008-06-16
Enrollment: 76
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. 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.
3. Age ≥18 and ≤80 years old.
4. ECOG ≤1
5. 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
6. 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)
7. Patient must have recovered from the side effects of previous chemotherapy, surgery, or radiation therapy for early breast cancer.

Exclusion Criteria:

1. History of radiation to the vaginal area
2. Concurrent treatment with any type of oral, injectable or topical form of estrogen or androgen therapy including natural supplements marketed as hormone replacement products
3. 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.
4. Use of vaginal hormonal products (rings, inserts, creams, gels) containing estrogens or androgens within the past 30 days.
5. History of an abnormal pap smear within the last 12 months
6. History of endometrial or ovarian cancer
7. Any episode of vaginal bleeding in the past 6 months that has not been evaluated by a gynecological exam and/or pelvic ultrasound
8. 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.)
9. 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.
10. Use of any investigational agent for breast cancer within 3 weeks of study entry.

Primary outcomes:
measure: Persistently Elevated Serum Estradiol Level Outside the Post-menopausal Range
timeFrame: 12 Weeks
Secondary outcomes:
measure: Serum Estradiol (E2)
timeFrame: 12 weeks
measure: Matched E2 by Commercial and Research (RIA) Analyses
timeFrame: baseline, 4 weeks
measure: Total Testosterone Levels
timeFrame: 12 weeks
measure: Sexual Quality of Life
timeFrame: Baseline, Week 4, Week 12
measure: Sexual Satisfaction
timeFrame: Baseline, Week 4, Week 12
measure: Change in Vaginal Epithelium Scores
timeFrame: Baseline, 12 weeks
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
Study officials:
affiliation: University of California, San Francisco
name: Michelle Melisko, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Melisko ME, Goldman ME, Hwang J, De Luca A, Fang S, Esserman LJ, Chien AJ, Park JW, Rugo HS. Vaginal Testosterone Cream vs Estradiol Vaginal Ring for Vaginal Dryness or Decreased Libido in Women Receiving Aromatase Inhibitors for Early-Stage Breast Cancer: A Randomized Clinical Trial. JAMA Oncol. 2017 Mar 1;3(3):313-319. doi: 10.1001/jamaoncol.2016.3904.