Letrozole and Goserelin or Leuprolide in Treating Premenopausal Estrogen Receptor-Positive Patients With Stage IV 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: NCT00498901
Recruitment Status : Terminated
First Posted : July 11, 2007
Last Update Posted : May 9, 2013
National Cancer Institute (NCI)
Information provided by:
University of Washington

Brief Summary:

RATIONALE: Aromatase inhibitors, such as letrozole, prevent the formation of estradiol, a female hormone. Giving letrozole together with goserelin, leuprolide, or surgery may be an effective treatment in women with hormone-dependent breast cancer.

PURPOSE: This phase II trial is studying how well giving letrozole together with goserelin or leuprolide works in treating premenopausal estrogen receptor-positive patients with stage IV breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: goserelin Drug: letrozole Drug: leuprolide acetate Procedure: conventional surgery Phase 2

Detailed Description:



  • To measure overall response rate (ORR) in premenopausal women treated with an aromatase inhibitor (AI) and ovarian suppression (OS).


  • To measure time to treatment failure (TTF) in premenopausal women treated with an AI and OS.
  • To measure time to progression (TTP) in premenopausal women treated with an AI and OS.
  • To measure time to death in premenopausal women treated with an AI and OS.
  • To assess the clinical benefit rate (CBR) in premenopausal women treated with an AI and OS.
  • To measure the qualitative and quantitative toxicity of an AI and OS.
  • To determine whether ORR, TTP, and CBR are similar to what is seen in postmenopausal women treated with an AI.
  • To determine whether ORR, TTP, and CBR are similar to what is seen in premenopausal women treated with tamoxifen and OS.
  • To determine if levels of estrogen (i.e., estradiol or estrone) are adequately suppressed in premenopausal women on an AI and OS.

OUTLINE: This is a pilot, open-label study.

Patients undergo surgical ovarian suppression (OS) or medical OS with luteinizing hormone-releasing hormone (LHRH) agonist (i.e., goserelin or leuprolide acetate, intramuscularly once monthly for 3 months and then every 2 months thereafter for the duration of study therapy). Beginning on day 14 after initiation of LHRH-agonist therapy or surgery, patients receive oral letrozole once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Menopausal status is tested periodically during study by measuring serum estradiol levels. Patients not converting to a menopausal state after the first month of study therapy, receive a higher dose of LHRH and undergo repeat estradiol testing in the second month. If the patient continues to be premenopausal, they are then considered for bilateral salpingo-oophorectomy or removed from study.

After completion of study therapy, patients are followed every 3 months for 2 years, every 6 months for 2 years, and annually thereafter.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Pilot of Aromatase Inhibitor Therapy With Femara® (Letrozole) and Ovarian Suppression in Premenopausal Estrogen Receptor Positive Women With Stage IV Carcinoma of the Breast
Study Start Date : February 2007
Actual Primary Completion Date : December 2007
Actual Study Completion Date : November 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Primary Outcome Measures :
  1. Overall response rate as measured by RECIST

Secondary Outcome Measures :
  1. Time to treatment failure
  2. Time to progression
  3. Time to death
  4. Clinical benefit rate
  5. Qualitative and quantitative toxicity as assessed by NCI CTCAE v3.0
  6. Disease-free survival
  7. Overall survival
  8. Safety
  9. Comparison of response with results of previous studies of postmenopausal women treated with aromatase inhibitor (AI) therapy and of premenopausal women treated with ovarian suppression (OS) and tamoxifen
  10. Determination of adequacy of estrogen suppression by AI therapy and OS

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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


  • Histologically confirmed carcinoma of the breast

    • Metastatic disease
  • Measurable disease (i.e., unidimensional by RECIST)
  • No rapidly progressing visceral involvement (e.g., liver or lymphangitic lung disease)
  • No known marrow involvement as evidenced by diffuse uptake by imaging studies or bone marrow biopsy or aspirate
  • No evidence of CNS metastases
  • Estrogen- and/or progesterone-receptor positive status confirmed in primary breast tumor or in recent biopsy of metastatic site


  • Female
  • Premenopausal*, as defined by the following criteria:

    • Less than 12 months from last menstrual period or premenopausal estradiol within the past 12 months
    • No prior bilateral oophorectomy
    • 45 years old or younger with intact ovaries and not a candidate for aromatase inhibitor therapy alone due to the potential for recurrent ovarian function NOTE: *Women are considered premenopausal after prior hysterectomy if they have intact ovaries and follicular hormone levels consistent with the institutional normal values for the premenopausal state
  • Women meeting premenopausal criteria prior to receiving ovarian suppression are eligible
  • ECOG performance status 0-2
  • Life expectancy ≥ 3 months
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective nonhormonal contraception during and for 12 weeks after discontinuation of study therapy
  • ANC ≥ 500 cells/mm³
  • Platelet count ≥ 50,000 cells/mm³
  • Hematocrit ≥ 28%
  • In the absence of liver metastases:

    • AST and ALT ≤ 2.5 times upper limit of normal (ULN)
    • Alkaline phosphatase ≤ 2.5 times ULN
  • In the presence of liver metastases:

    • AST and ALT ≤ 5 times ULN
    • Alkaline phosphatase ≤ 5 times ULN
  • In the presence of bone metastases:

    • AST and ALT ≤ 10 times ULN
    • Alkaline phosphatase ≤ 10 times ULN
  • Total bilirubin ≤ 2 times ULN
  • No significant comorbid conditions, including any of the following:

    • Clinically significant cardiac disease not well controlled with medication (e.g., congestive heart failure, symptomatic coronary artery disease, or cardiac arrhythmias)
    • Myocardial infarction within the past 12 months
    • Serious concurrent infection
  • No lack of physical integrity of the upper gastrointestinal tract
  • No inability to swallow or malabsorption syndrome
  • No other carcinoma within the past 5 years except nonmelanoma skin cancer and treated in situ cervical cancer
  • No mental illness
  • No known hypersensitivity to luteinizing hormone-releasing hormone (LHRH), LHRH-agonist analogues, or any of the components in goserelin


  • No concurrent chemotherapy and/or additional hormonal therapy
  • Concurrent trastuzumab (Herceptin®) for patients with HER2 overexpression allowed

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): NCT00498901

United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109-1023
University Cancer Center at University of Washington Medical Center
Seattle, Washington, United States, 98195-6043
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
Principal Investigator: Hannah M. Linden, MD University of Washington

Responsible Party: Hannah M. Linden, University Cancer Center at University of Washington Medical Center Identifier: NCT00498901     History of Changes
Other Study ID Numbers: 6412
UWCC-UW 6412
UWCC- 06-4560-H/D
CDR0000553612 ( Registry Identifier: pdq )
First Posted: July 11, 2007    Key Record Dates
Last Update Posted: May 9, 2013
Last Verified: May 2013

Keywords provided by University of Washington:
stage IV breast cancer
recurrent breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
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
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Antineoplastic Agents, Hormonal