Neoadjuvant Letrozole in Treating Postmenopausal Women With Estrogen-Receptor Positive and/or Progesterone-Receptor Positive Stage II, Stage IIIA, or Stage IIIB Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00084396
First received: June 10, 2004
Last updated: April 4, 2014
Last verified: April 2014
  Purpose

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by reducing the production of estrogen. Giving letrozole before surgery may shrink the tumor so that it can be removed.

PURPOSE: This phase II trial is studying how well neoadjuvant letrozole works in treating postmenopausal women who are undergoing surgery for estrogen-receptor positive or progesterone-receptor positive stage II, stage IIIA, or stage IIIB breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: letrozole
Procedure: conventional surgery
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Trial Of 4 Months Preoperative Letrozole 2.5 mg Daily For Postmenopausal Women With Estrogen Receptor Positive And/Or Progesterone Receptor Positive T2, T3, T4a-c, N0-2, M0 Breast Cancer- Novel Biomarkers for Aromatase Inhibitor Therapy

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Predictive model for response as assessed by gene expression profiling [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate [ Designated as safety issue: No ]
  • Changes in Ki67 proliferation rates [ Designated as safety issue: No ]
  • Rate of improvement in surgical outcomes [ Designated as safety issue: No ]
  • Long-term outcomes [ Designated as safety issue: No ]
  • Safety [ Designated as safety issue: Yes ]
  • Mechanisms of resistance [ Designated as safety issue: No ]

Enrollment: 115
Study Start Date: October 2003
Estimated Study Completion Date: March 2017
Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Letrozole/Surgery Drug: letrozole Procedure: conventional surgery

Detailed Description:

OBJECTIVES:

Primary

  • Develop a predictive model of response (based on gene expression profiling) in postmenopausal women with estrogen- and/or progesterone-receptor positive stage II, IIIA, or IIIB breast cancer treated with neoadjuvant letrozole.

Secondary

  • Determine the response rate in patients treated with this drug.
  • Determine changes in Ki67 proliferation rates in patients treated with this drug.
  • Determine the rate of improvement in surgical outcomes in patients treated with this drug.
  • Determine the long-term outcomes in patients treated with this drug.
  • Determine the safety of this drug in these patients.
  • Determine mechanisms of resistance to this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive neoadjuvant oral letrozole once daily for 16 weeks in the absence of disease progression. Patients then undergo breast surgery one day after the last dose of letrozole. Patients with partial response after 16 weeks may continue to receive letrozole for an additional 8 weeks before undergoing breast surgery.

Patients are followed within 4 weeks after definitive surgery and then annually for 10 years.

PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed infiltrating adenocarcinoma of the breast by core needle biopsy

    • Clinical stage T2-T4a-c, N0-2, M0
  • Palpable and measurable disease
  • Previously untreated disease
  • Benefits from neoadjuvant therapy that would improve surgical outcome AND meets criteria for 1 of the following:

    • Marginal candidate for lumpectomy (e.g., lumpectomy feasible but patient at risk for positive margins or poor cosmetic outcome) AND patient desires breast-conserving surgery
    • Ineligible for lumpectomy due to size of primary tumor, but modified radical mastectomy feasible AND patient desires breast-conserving surgery
    • Inoperable disease AND systemic therapy required for disease to become operable by modified radical mastectomy
  • Bilateral primary tumors allowed provided both tumors are consistent with entry criteria
  • No inflammatory carcinoma (defined as peau d' orange affecting at least one third of the breast)

    • Direct extension of the tumor to the skin allowed
  • No metastatic breast disease, except isolated ipsilateral supraclavicular lymphadenopathy
  • Hormone receptor status:

    • Estrogen- and/or progesterone-receptor positive disease based on 10% or more nuclear staining of the invasive component of the tumor

PATIENT CHARACTERISTICS:

Age

  • Postmenopausal

Sex

  • Female

Menopausal status

  • Postmenopausal, defined as meeting 1 of the following criteria:

    • Cessation of menstrual periods for at least 1 year
    • Bilateral surgical oophorectomy
    • Follicle-stimulating hormone and estradiol levels in the postmenopausal range

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • No severe liver dysfunction that would preclude study participation

Renal

  • Not specified

Other

  • Willing and able to provide biopsy material
  • Willing to undergo breast surgery after neoadjuvant treatment
  • No condition (e.g., confusion, infirmity, or alcoholism) that would preclude study compliance
  • No other concurrent active and progressive invasive malignancies
  • No other concurrent severe disease that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent immunotherapy or biological response modifiers for breast cancer

Chemotherapy

  • No prior chemotherapy for breast cancer
  • No concurrent chemotherapy for breast cancer

Endocrine therapy

  • At least 2 weeks since prior hormone replacement therapy or phytoestrogenic herbal, alternative, or over-the-counter (OTC) sex hormone remedies
  • No prior hormonal agents for breast cancer
  • No prior aromatase inhibitors, tamoxifen, raloxifene, or other antiestrogen or selective estrogen receptor modulators
  • No concurrent drugs known to affect sex hormone status, including hormone replacement therapy or phytoestrogenic herbal, alternative, or OTC remedies
  • No other concurrent endocrine therapy for breast cancer

Radiotherapy

  • No prior radiotherapy for breast cancer
  • No concurrent radiotherapy for breast cancer

Surgery

  • Prior sentinel node biopsy allowed
  • No other concurrent surgery for breast cancer

Other

  • More than 30 days since prior non-approved or experimental drugs
  • Concurrent bisphosphonates for osteoporosis allowed
  • No other concurrent treatment for breast cancer
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00084396

Locations
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Matthew J. Ellis, MD, PhD, FRCP Washington University Siteman Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00084396     History of Changes
Other Study ID Numbers: CDR0000361963, R01CA095614, P30CA091842, WU-03-0586, UCSF-02755, UCSF-H8409-21398-04
Study First Received: June 10, 2004
Last Updated: April 4, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Washington University School of Medicine:
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Estrogens
Progesterone
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Progestins

ClinicalTrials.gov processed this record on September 30, 2014