Extended Endocrine Therapy for Premenopausal Women With Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00903162
Recruitment Status : Completed
First Posted : May 18, 2009
Results First Posted : February 4, 2016
Last Update Posted : April 18, 2016
Beth Israel Deaconess Medical Center
Information provided by (Responsible Party):
Ann H. Partridge, MD, MPH, Dana-Farber Cancer Institute

Brief Summary:
The purpose of this study is to determine the safety and tolerability of the combination of two drugs (letrozole and leuprolide) in women who have already taken tamoxifen for at least 4.5 years. Letrozole, an aromatase inhibitor (which blocks an enzyme that produces estrogen), is a drug that is FDA approved. It has been shown to reduce the risk of breast cancer recurrence in postmenopausal women with breast cancer who have been previously treated with tamoxifen. Letrozole works by stopping the production of estrogen in parts of the body other than the ovaries. Leuprolide is a drug that stops a women's ovarian cycles. This process is known as ovarian function suppression. Stopping a women's menstrual cycle may be effective against breast cancer for some patients when given as initial therapy. The combination of letrozole and leuprolide is considered a standard treatment for women with metastatic breast cancer, and is also sometimes used for treatment of premenopausal early stage breast cancer, but it has not been accepted as a standard of care treatment.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: leuprolide Drug: letrozole Drug: zoledronic acid Phase 2

Detailed Description:
  • Participants will be given a monthly intramuscular injection of leuprolide. Six to eight weeks after the first leuprolide injection, participants will be instructed to begin taking letrozole pills by mouth at home each day.
  • During this research study, participants will also be offered injections of zoledronic acid to preserve bone mineral density. If desire, these injections will be given every 6 months for a total of 4 injections during the course of the research study.
  • The treatments in this research study may increase the risk of bone density loss, so vitamin D and calcium supplements will be recommended to participants.
  • The following tests and procedures will be performed during the research study: Physical Exam (every visit); Blood tests; Urine test (beginning and end of treatment); Imaging (annual mammograms); Bone Density (DXA) Scan (beginning and end of treatment); Questionnaires (throughout the study).
  • Participants will be on this study for about two years.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Extended Endocrine Therapy for Premenopausal Women With Breast Cancer
Study Start Date : May 2009
Actual Primary Completion Date : July 2014
Actual Study Completion Date : September 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Letrozole-Leuprolide
Patients will receive 2.5mg oral letrozole daily and either 7.5mg monthly of Leuprolide IM or 22.5mg every three months of Leuprolide IM. Zoledronic acid 4mg IV every 6 months x 4 will also be offered optionally.
Drug: leuprolide
Given intramuscularly beginning on day 1 and then either 7.5 mg every month or 22.5 mg every 3 months for two years
Other Name: Lupron
Drug: letrozole
Taken orally once a day 6-8 weeks after initial leuprolide administration
Other Name: Femara
Drug: zoledronic acid
If desired, given intravenously every 6 months for a total of 4 injections (optional)
Other Name: Zometa

Primary Outcome Measures :
  1. Tolerability at One Year of Ovarian Function Suppression (OFS) Using Leuprolide and Letrozole. [ Time Frame: 1 year ]
    The tolerability at one year of ovarian function suppression (OFS) using leuprolide and letrozole in this patient population. Specifically, the number of patients who discontinued treatment prior to one year due to toxicity.

Secondary Outcome Measures :
  1. Ovarian Function Suppression (OFS) Combined With Aromatase Inhibition Combined With Intravenous Bisphosphonate Therapy on Bone Mineral Density. [ Time Frame: 2 years ]
    Ovarian function suppression (OFS) combined with aromatase inhibition combined with intravenous bisphosphonate therapy on bone mineral density in this patient population.

  2. The Effect of OFS Combined With Aromatase Inhibitor Therapy on the Incidence and Severity of Menopausal Symptoms, Sexual Dysfunction, Musculoskeletal Complaints, Other Side Effects and Overall Quality of Life. [ Time Frame: 2 years ]
    OFS combined with aromatase inhibitor therapy on the incidence and severity of menopausal symptoms, sexual dysfunction, musculoskeletal complaints, other side effects and overall quality of life in this population.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Women 18 years of age or older
  • History of invasive ER+ or PR+ breast cancer treated with at least 4.5 years of tamoxifen
  • No current evidence of recurrent invasive disease or metastatic disease. Patients may have a history of bilateral breast cancer
  • Premenopausal (estradiol level in premenopausal range, >20pg/ml, within the prior 28 days)
  • Liver function tests and creatinine <2.5 times the upper limit of normal within the 28 days prior to enrollment
  • ECOG Performance Status 0-1
  • Must agree to use non-hormonal contraception (condoms, diaphragm, IUD, sterilization, abstinence, etc) and no other hormonal therapy during trial and until 3 months after letrozole is stopped
  • Negative pregnancy test within 14 days prior to enrollment
  • Patient must be able to speak, read and write in English

Exclusion Criteria:

  • Previous treatment with an oral or IV bisphosphonate in the prior two years
  • History of cancer other than breast cancer within 5 years excluding basal/squamous cell skin carcinoma in situ of the cervix
  • Women with evidence of current local recurrence or metastatic breast cancer
  • Pregnant women
  • Nursing women
  • Women who are currently taking tamoxifen and are unwilling to stop this medication
  • Women with a known deleterious BRCA 1 or BRCA 2 mutation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00903162

United States, Colorado
University of Colorado
Denver, Colorado, United States, 80217
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Newton Wellesley Hospital
Newton, Massachusetts, United States, 02462
Sponsors and Collaborators
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
Principal Investigator: Ann Partridge, MD Dana-Farber Cancer Institute

Responsible Party: Ann H. Partridge, MD, MPH, Principal Investigator, Dana-Farber Cancer Institute Identifier: NCT00903162     History of Changes
Other Study ID Numbers: 08-280
First Posted: May 18, 2009    Key Record Dates
Results First Posted: February 4, 2016
Last Update Posted: April 18, 2016
Last Verified: January 2016

Keywords provided by Ann H. Partridge, MD, MPH, Dana-Farber Cancer Institute:
hormone-receptor positive
zoledronic acid

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Zoledronic acid
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Bone Density Conservation Agents
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Antineoplastic Agents, Hormonal