Extended Endocrine Therapy for Premenopausal Women With Breast Cancer

NCT00903162 | Completed Phase 2 Results DMC

• 1 other identifier: 08-280
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 4

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.

Conditions

Breast Cancer

Keywords

hormone-receptor positive; tamoxifen; letrozole; zoledronic acid; leuprolide

Outcome Measures

Primary Outcomes (1)

• Tolerability at One Year of Ovarian Function Suppression (OFS) Using Leuprolide and Letrozole.

  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.

  1 year

Secondary Outcomes (2)

• Ovarian Function Suppression (OFS) Combined With Aromatase Inhibition Combined With Intravenous Bisphosphonate Therapy on Bone Mineral Density.

  2 years

• 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.

  2 years

Study Arms (1)

Letrozole-Leuprolide

EXPERIMENTAL

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; Drug: letrozole; Drug: zoledronic acid

Interventions

leuprolide DRUG

Given intramuscularly beginning on day 1 and then either 7.5 mg every month or 22.5 mg every 3 months for two years

Also known as: Lupron

Letrozole-Leuprolide

letrozole DRUG

Taken orally once a day 6-8 weeks after initial leuprolide administration

Also known as: Femara

Letrozole-Leuprolide

zoledronic acid DRUG

If desired, given intravenously every 6 months for a total of 4 injections (optional)

Also known as: Zometa

Letrozole-Leuprolide

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Beth Israel Deaconess Medical Center: collaborator
• Novartis: collaborator

Study Sites (4)

University of Colorado

Denver, Colorado, 80217, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Newton Wellesley Hospital

Newton, Massachusetts, 02462, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Leuprolide; Letrozole; Zoledronic Acid

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Imidazoles

Results Point of Contact

• Title: Ann Partridge, MD, MPH
• Organization: Dana-Farber Cancer Institute

ann_partridge@dfci.harvard.edu

617.632.3800

Study Officials

• Ann Partridge, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 5, 2009
• First Posted: May 18, 2009
• Study Start: May 1, 2009
• Primary Completion: July 1, 2014
• Study Completion: September 1, 2014
• Last Updated: April 18, 2016
• Results First Posted: February 4, 2016

Record last verified: 2016-01

Locations

US (4)