Back to results

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

Primary Purpose

Breast Cancer

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

goserelin

letrozole

leuprolide acetate

conventional surgery

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring stage IV breast cancer, recurrent breast cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept 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

Sites / Locations

Seattle Cancer Care Alliance
University Cancer Center at University of Washington Medical Center

Outcomes

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

Full Information

NCT ID

NCT00498901

First Posted

July 10, 2007

Last Updated

May 7, 2013

Sponsor

University of Washington

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00498901

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

May 2013

Overall Recruitment Status

Terminated

Study Start Date

February 2007 (undefined)

Primary Completion Date

December 2007 (Actual)

Study Completion Date

November 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

University of Washington

Collaborators

National Cancer Institute (NCI)

4. Oversight

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

stage IV breast cancer, recurrent breast cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Masking

None (Open Label)

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

goserelin

Intervention Type

Drug

Intervention Name(s)

letrozole

Intervention Type

Drug

Intervention Name(s)

leuprolide acetate

Intervention Type

Procedure

Intervention Name(s)

conventional surgery

Primary Outcome Measure Information:

Title

Overall response rate as measured by RECIST

Secondary Outcome Measure Information:

Title

Time to treatment failure

Title

Time to progression

Title

Time to death

Title

Clinical benefit rate

Title

Qualitative and quantitative toxicity as assessed by NCI CTCAE v3.0

Title

Disease-free survival

Title

Overall survival

Title

Safety

Title

Determination of adequacy of estrogen suppression by AI therapy and OS

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hannah M. Linden, MD

Organizational Affiliation

University of Washington

Official's Role

Principal Investigator

Facility Information:

Facility Name

Seattle Cancer Care Alliance

City

Seattle

State/Province

Washington

ZIP/Postal Code

98109-1023

Country

United States

Facility Name

University Cancer Center at University of Washington Medical Center

City

Seattle

State/Province

Washington

ZIP/Postal Code

98195-6043

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs