Letrozole and Goserelin or Leuprolide in Treating Premenopausal Estrogen Receptor-Positive Patients With Stage IV Breast Cancer

Sponsor

University of Washington (Other)

Overall Status

Terminated

CT.gov ID

NCT00498901

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Duration (Months)

0.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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

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.

Study Design

Study Type:

Interventional

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 :

Feb 1, 2007

Actual Primary Completion Date :

Dec 1, 2007

Actual Study Completion Date :

Nov 1, 2008

Outcome Measures

Primary Outcome Measures

Overall response rate as measured by RECIST []

Secondary Outcome Measures

Time to treatment failure []
Time to progression []
Time to death []
Clinical benefit rate []
Qualitative and quantitative toxicity as assessed by NCI CTCAE v3.0 []
Disease-free survival []
Overall survival []
Safety []
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 []
Determination of adequacy of estrogen suppression by AI therapy and OS []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109-1023
2	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195-6043