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
18 Years
N/A
Female
Breast Cancer
Trial Information
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
OBJECTIVES:
Primary
- To measure overall response rate (ORR) in premenopausal women treated with an aromatase
inhibitor (AI) and ovarian suppression (OS).
Secondary
- 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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- 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
PATIENT CHARACTERISTICS:
- 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
PRIOR CONCURRENT THERAPY:
- No concurrent chemotherapy and/or additional hormonal therapy
- Concurrent trastuzumab (Herceptin®) for patients with HER2 overexpression allowed
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Overall response rate as measured by RECIST
Safety Issue:
No
Principal Investigator
Hannah M. Linden, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Washington
Authority:
United States: Federal Government
Study ID:
6412
NCT ID:
NCT00498901
Start Date:
February 2007
Completion Date:
November 2008
Related Keywords:
- Breast Cancer
- stage IV breast cancer
- recurrent breast cancer
- Breast Neoplasms
Name | Location |
|---|---|
| University Cancer Center at University of Washington Medical Center | Seattle, Washington 98195 |
| Seattle Cancer Care Alliance | Seattle, Washington 98109 |
