Extended Endocrine Therapy for Premenopausal Women With Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Beth Israel Deaconess Medical Center
Novartis
Information provided by (Responsible Party):
Ann H. Partridge, MD, MPH, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00903162
First received: May 5, 2009
Last updated: March 6, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Breast Cancer
Drug: leuprolide
Drug: letrozole
Drug: zoledronic acid
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Extended Endocrine Therapy for Premenopausal Women With Breast Cancer

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • To determine the tolerability at one year of ovarian function suppression (OFS) using leuprolide and letrozole in this patient population. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To explore the effect of ovarian function suppression (OFS) combined with aromatase inhibition combined with intravenous bisphosphonate therapy on bone mineral density in this patient population. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To evaluate 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 in this population. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 17
Study Start Date: May 2009
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00903162

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

No publications provided

Responsible Party: Ann H. Partridge, MD, MPH, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00903162     History of Changes
Other Study ID Numbers: 08-280
Study First Received: May 5, 2009
Last Updated: March 6, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
hormone-receptor positive
tamoxifen
letrozole
zoledronic acid
leuprolide

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Leuprolide
Letrozole
Zoledronic acid
Diphosphonates
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on August 25, 2014