- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00084396
Neoadjuvant Letrozole in Treating Postmenopausal Women With Estrogen-Receptor Positive and/or Progesterone-Receptor Positive Stage II, Stage IIIA, or Stage IIIB Breast Cancer
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
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Missouri
-
Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Letrozole/Surgery
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
---|
Predictive model for response as assessed by gene expression profiling
|
Secondary Outcome Measures
Outcome Measure |
---|
Response rate
|
Safety
|
Changes in Ki67 proliferation rates
|
Rate of improvement in surgical outcomes
|
Long-term outcomes
|
Mechanisms of resistance
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Michael Naughton, M.D., Washington University School of Medicine
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Hormone Antagonists
- Aromatase Inhibitors
- Steroid Synthesis Inhibitors
- Estrogen Antagonists
- Letrozole
Other Study ID Numbers
- CDR0000361963
- P30CA091842 (U.S. NIH Grant/Contract)
- R01CA095614 (U.S. NIH Grant/Contract)
- WU-03-0586
- UCSF-02755
- UCSF-H8409-21398-04
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Breast Cancer
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI); Rutgers Cancer Institute of New JerseyActive, not recruitingStage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative Breast CancerUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedMale Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
University of WashingtonTerminatedBreast Cancer | Breast Cancer Stage I | Breast Cancer Stage II | Breast Cancer Stage III | Breast Cancer Stage IIB | Breast Cancer Stage IIA | Breast Cancer Stage IIIA | Breast Cancer Stage IIIB | Breast Cancer Stage IIIcUnited States
-
CelgeneCompletedBreast Cancer | Metastatic Breast Cancer | Stage IV Breast Cancer | Triple-negative Breast Cancer | Recurrent Breast Cancer | Breast Tumor | Cancer of the Breast | Triple-negative Metastatic Breast Cancer | Estrogen Receptor- Negative Breast Cancer | HER2- Negative Breast Cancer | Progesterone Receptor- Negative...United States, United Kingdom, Italy, Germany, Spain, Canada, Portugal, Australia, Austria, Greece, Brazil, France
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedHER2-positive Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
University of WashingtonNational Cancer Institute (NCI)CompletedHER2-positive Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Estrogen Receptor-negative Breast Cancer | Estrogen Receptor-positive Breast Cancer | Progesterone Receptor-negative Breast Cancer | Progesterone Receptor-positive Breast...United States
-
University of WashingtonNational Cancer Institute (NCI)CompletedHER2-positive Breast Cancer | Male Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
Sidney Kimmel Cancer Center at Thomas Jefferson...Susan G. Komen Breast Cancer FoundationCompletedStage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative Breast CancerUnited States
-
Northwestern UniversityEisai Inc.UnknownMale Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative...United States
-
Ohio State University Comprehensive Cancer CenterCompletedStage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast Cancer | Stage III Breast CancerUnited States
Clinical Trials on conventional surgery
-
Shanghai Changzheng HospitalNaval Specialty Medical Center, China; The NO.72 Army Hospital of Huzhou, China and other collaboratorsNot yet recruitingDegenerative Cervical Kyphosis With StenosisChina
-
University of BelgradeCompleted
-
National Medical Research Council (NMRC), SingaporeUnknownColorectal CancerChina, Singapore
-
Instituto do Cancer do Estado de São PauloUnknownHead and Neck Cancer | Gastric Cancer | Pancreatic Cancer | Esophageal Cancer | Lung Cancer | Rectal Cancer | Prostate Cancer | Bladder Cancer | Renal Cancer | Uterus CancerBrazil
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Adenosquamous Carcinoma | Cervical Squamous Cell Carcinoma | Recurrent Cervical Carcinoma | Cervical Small Cell CarcinomaUnited States, Spain
-
European Organisation for Research and Treatment...Eastern Cooperative Oncology Group; NCIC Clinical Trials Group; Southwest Oncology... and other collaboratorsCompleted
-
Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI)Completed
-
European Organisation for Research and Treatment...CompletedProstate CancerBelgium, Italy, Slovakia
-
Southwest Oncology GroupNational Cancer Institute (NCI); American College of SurgeonsCompletedSarcomaUnited States