Vaginal Testosterone Cream vs ESTRING for Vaginal Dryness or Decreased Libido in Early Stage Breast Cancer Patients (E-String)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00698035
First received: June 11, 2008
Last updated: May 27, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Sexual Dysfunction, Physiological
Drug: Testosterone Cream
Drug: Estring
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Supportive Care
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

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Persistently Elevated Serum Estradiol Level Outside the Post-menopausal Range [ Time Frame: 12 Weeks ] [ Designated as safety issue: Yes ]
    Liquid chromatography tandem mass spectrometry (Quest Diagnostics). Persistently elevated serum estradiol level outside the post-menopausal range was defined as: Serum estradiol >10 pg/dl on two consecutive collections at least 4 weeks apart. 2. If baseline estradiol was >10 pg/dl, subsequent levels >10 pg/ml higher than baseline were considered a significant elevation outside the post-menopausal range.


Secondary Outcome Measures:
  • Serum Estradiol (E2) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    serial measurements of serum estradiol (E2) by liquid chromatography tandem mass spectrometry (Quest Diagnostics)

  • Matched E2 by Commercial and Research (RIA) Analyses [ Time Frame: baseline, 4 weeks ] [ Designated as safety issue: No ]
    Serum estradiol assays sent to the UCSF clinical laboratory are sent out to Quest Diagnostics, which uses LC/MS for their ultra-sensitive estradiol assay. Samples were also sent to a specialized research lab in England which has developed an ultrasensitive assay using radioimmunoassay (RIA) after ether extraction (sensitivity limit of 3pmol/l) to quantify low levels of estradiol found in post-menopausal women

  • Total Testosterone Levels [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    By serum ultrasensitive total testosterone test (Quest Diagnostics)

  • Sexual Quality of Life [ Time Frame: Baseline, Week 4, Week 12 ] [ Designated as safety issue: No ]
    Cancer Rehabilitation Evaluation System (CARES) Sexual Dysfunction (SD) and Sexual Interest (SI) Subscales range from 0 to 4 and measure the severity of problems, with higher scores indicating more difficulty.

  • Sexual Satisfaction [ Time Frame: Baseline, Week 4, Week 12 ] [ Designated as safety issue: No ]
    Participants were asked to respond to a Sexual Satisfaction One Item Measure which asked "Overall, how satisfactory to you is your sexual relationship with your partner?" Response options range from 1 (Extremely unsatisfactory) to 6 (Extremely satisfactory).

  • Change in Vaginal Epithelium Scores [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
    During a gynecologic exam, the vaginal epithelium was assessed by an examiner using the Vaginal Atrophy Scoring Scale to evaluate Rugae (lack of), Pallor (pinkness), Petechiae, Mucosal thinning, Dryness. Scores range from 0 (none) to 3 (severe); higher scores indicate less favorable outcomes.


Enrollment: 76
Study Start Date: March 2007
Study Completion Date: December 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Testosterone Cream
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: 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
Other Name: intravaginal testosterone cream
Active Comparator: Estring
Estring 2mg ring inserted vaginally once every 12 weeks
Drug: Estring
2mg ring inserted vaginally once every 12 weeks
Other Name: ESTRING Estrodial Vaginal Ring

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00698035

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Michelle Melisko, MD University of California, San Francisco
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00698035     History of Changes
Other Study ID Numbers: UCSF-067519
Study First Received: June 11, 2008
Results First Received: April 29, 2014
Last Updated: May 27, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
Vaginal Testosterone Cream
ESTRING

Additional relevant MeSH terms:
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Breast Neoplasms
Sexual Dysfunction, Physiological
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Genital Diseases, Male
Genital Diseases, Female
Estradiol
Polyestradiol phosphate
Estradiol valerate
Estradiol 17 beta-cypionate
Estradiol 3-benzoate
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anabolic Agents
Estrogens
Contraceptive Agents
Reproductive Control Agents

ClinicalTrials.gov processed this record on September 30, 2014