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”

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.

Study Type: Interventional

Study Design: Supportive Care, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2009

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.

Intervention(s) in this Clinical Trial

• Drug: 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: Estring
  • 2mg ring inserted vaginally once every 12 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: I
  • 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
• Active Comparator: II
  • Estring 2mg ring inserted vaginally once every 12 weeks

Primary Measures

• Evaluate safety, based on serial measurements of serum estradiol levels, of testosterone cream or the ESTRING administered for relief of vaginal dryness and/or decreased libido related to aromatase inhibitor therapy in early breast cancer patients
  • Time Frame: Study Completion
    Safety Issue?: Yes

Secondary Measures

• Document the systemic estradiol and testosterone levels at several time points
  • Time Frame: Study Completion
    Safety Issue?: No
• Compare standard clinical laboratory measurements of serum estradiol with values of serum estradiol as measured by an ultrasenstive assay in a research laboratory
  • Time Frame: Study Completion
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of California, San Francisco

Overall Clinical Trial Officials and Contacts

Michelle Melisko, MD Principal Investigator University of California, San Francisco  

Overall Contact: Diane Davies 877-827-3222 

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00698035

Study ID Number: UCSF-067519

ClinicalTrials.gov Identifier: NCT00698035

Health Authority: United States: Institutional Review Board