Fulvestrant or Tamoxifen in Treating Postmenopausal Women Who Are Undergoing Surgery for Ductal Carcinoma in Situ of the Breast

A Pilot Clinical Trial to Evaluate the Biological Activity of Fulvestrant (Faslodex) in Breast Ductal Carcinoma (DCIS)

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant or tamoxifen may fight breast cancer by blocking the use of estrogen by the tumor cells. Giving fulvestrant or tamoxifen before surgery may be an effective treatment for breast cancer.

PURPOSE: This randomized clinical trial is studying how well giving fulvestrant or tamoxifen works in treating postmenopausal women who are undergoing surgery for ductal carcinoma in situ of the breast.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Procedure: neoadjuvant therapy; Procedure: conventional surgery; Drug: tamoxifen citrate; Drug: fulvestrant

Detailed Description

OBJECTIVES:

Primary

• Determine, preliminarily, the efficacy of neoadjuvant fulvestrant, in terms of molecular changes in markers of the estrogen pathway, cell proliferation and apoptosis, and the epidermal growth factor pathway, in postmenopausal women with newly diagnosed ductal carcinoma in situ of the breast.

Secondary

• Determine the toxicity profile of fulvestrant in these patients.

OUTLINE: This is a randomized, placebo-controlled, pilot, multicenter study. Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive oral placebo once daily on days 1-21.
• Arm II: Patients receive oral tamoxifen once daily on days 1-21.
• Arm III: Patients receive fulvestrant intramuscularly (IM) on day 1.
• Arm IV: Patients receive fulvestrant IM as in arm III but at a higher dose. In all arms, treatment continues in the absence of disease progression or unacceptable toxicity. All patients undergo surgical resection of the tumor on approximately day 21.

PROJECTED ACCRUAL: A total of 100 patients (25 per treatment arm) will be accrued for this study.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed ductal carcinoma in situ (DCIS) of the breast

  • T0 disease
  • Newly diagnosed disease by minimally invasive biopsy (e.g., a vacuum-assisted large core tool [mammotome] or an equivalent method)
• Biopsy tissue available for molecular marker analysis
• Baseline mammography performed within the past 8 weeks

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• Postmenopausal

Sex

• Female

Menopausal status

• Postmenopausal, as defined by 1 of the following:

  • Age ≥ 60
  • Age ≥ 45 AND amenorrheic for > 1 year with uterus intact
  • Underwent bilateral oophorectomy
  • Follicle-stimulating hormone and estradiol levels in postmenopausal range

Performance status

• SWOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 8.0 g/dL

Hepatic

• SGOT and/or SGPT ≤ 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2.5 times ULN
• Bilirubin ≤ 2.0 times ULN

Renal

• Creatinine ≤ 2.0 mg/dL

Cardiovascular

• No history of deep vein thrombosis

Pulmonary

• No history of pulmonary embolism

Other

• Negative pregnancy test (if clinically indicated)
• No peripheral neuropathy > grade 1
• No underlying medical, psychiatric, or social condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• More than 6 months since prior hormonal therapy, including any of the following:

  • Antiestrogens
  • Estrogen
  • Selective estrogen-receptor modulators
  • Progestins
  • Aromatase inhibitors

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No prior therapy for DCIS

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Molecular markers of the estrogen pathway as measured by immunohistochemistry at 3 weeks

Secondary Outcome Measures

Outcome Measure
Mammographic breast density as measured by the Madena method at 3 weeks

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center
• Investigators: Study Chair: Agustin Garcia, MD, Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start: November 1, 2004

Study Registration Dates

• First Submitted: August 2, 2005
• First Submitted That Met QC Criteria: August 2, 2005
• First Posted (Estimate): August 4, 2005

Study Record Updates

• Last Update Posted (Estimate): November 6, 2013
• Last Update Submitted That Met QC Criteria: November 5, 2013
• Last Verified: July 1, 2006

More Information

Terms related to this study

• Keywords: breast cancer in situ; ductal breast carcinoma in situ
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Ductal, Lobular, and Medullary; Carcinoma in Situ; Carcinoma; Carcinoma, Ductal; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Estrogen Receptor Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Fulvestrant; Tamoxifen
• Other Study ID Numbers: CDR0000430705; CSMC-00000244; CSMC-4415/CR00000244; ZENECA-CSMC-00000244; CSMC-1B-03-7