Letrozole in Treating Postmenopausal Women with Ductal Carcinoma in Situ

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IIBiomarker/Laboratory analysis, Diagnostic, Treatment18 and overCALGB 40903
NCI-2011-03452, CDR0000701992, NCT01439711

Trial Description

Summary

This phase II clinical trial studies how well letrozole works in treating women with ductal carcinoma in situ. Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by blocking the use of estrogen by the tumor cells or by lowering the amount of estrogen the body makes.

Further Study Information

PRIMARY OBJECTIVES:

I. To estimate the mean change in magnetic resonance imaging (MRI) tumor volume from pretreatment to completion of preoperative endocrine therapy in estrogen receptor-positive (ER+) ductal carcinoma in situ (DCIS), as well as to determine whether 3-month change in volume correlates with 6-month change.

SECONDARY OBJECTIVES:

I. To assess radiographic-pathologic correlation between MRI findings and histopathology, including the prevalence of occult invasive cancer in patients undergoing neoadjuvant endocrine therapy for DCIS.

II. To compare changes in (1) MRI maximum lesion diameter and (2) mammographic extent at baseline and following treatment. These are two additional radiographic parameters which may also detect biological response to therapy.

III. To determine practice patterns of adjuvant hormonal and radiation therapy in patients who complete neoadjuvant letrozole therapy for DCIS.

IV. To determine whether Ki67 is reduced with neoadjuvant letrozole treatment for DCIS, and to compare the reduction in proliferation between radiographic responders and non-responders.

V. To identify baseline immunohistochemistry (IHC) and expression biomarkers predictive of response to treatment, with response determined by extent of Ki67 reduction. Subsets showing the greatest reduction in Ki67 would be the most likely candidates for non-operative treatment in future studies.

VI. To examine whether germline polymorphisms are associated with clinical endpoints, including treatment-related toxicity or efficacy outcomes, or with expression of biomarkers in serum or tumor.

VII. To assess quality of life and musculoskeletal symptoms associated with neoadjuvant letrozole for ER positive DCIS.

OUTLINE:

Patients receive letrozole orally (PO) once daily (QD). Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity. Within 30 days of completion of letrozole, patients undergo mastectomy or lumpectomy. Patients with disease progression at 3 months, undergo mastectomy or lumpectomy.

After completion of study treatment, patients are followed up at 6 months.

Eligibility Criteria

Inclusion Criteria:

No prior surgical excision in the index breast for current DCIS diagnosis of DCIS

No contraindications to breast MRI

Patient has diagnostic tissue available for correlative studies

Clinical stage Tis or T1mi N0 M0

Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

Any exogenous hormone therapy must be completed 4 weeks prior to registration

Serum creatinine =< 1.7 mg/dL

Not pregnant or nursing

Bilirubin =< 2.0 mg/dL

No prior neoadjuvant/adjuvant therapy for DCIS diagnosis

Serum estradiol level assay (required for patients < 55 years of age and one year or more of amenorrhea) < 20 pg/mL

Pathologic confirmation of DCIS of the female breast without invasive cancer, with diagnosis rendered on core biopsy only, completed within 60 days before registration; patients diagnosed with DCIS on the basis of surgical biopsy are not eligible for this study

Patients with microinvasion on diagnostic core biopsy, defined as tumor =< 1mm in greatest dimension, will be allowed to participate

All patients must have a clip placed, either at the time of the diagnostic biopsy or at the time of the baseline MRI prior to the start of treatment

Patients must be postmenopausal defined as:

Age >= 55 years and one year or more of amenorrhea

Age < 55 years and one year or more of amenorrhea, with an estradiol assay < 20 pg/mL

Surgical menopause with bilateral oophorectomy (at least 28 days must elapse from surgery to time of study registration)

The use of gonadotropin-releasing hormone (GnRH) analogues to achieve postmenopausal status is not allowed

Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)

Any patients with a history of tamoxifen or raloxifene use within two years of current DCIS diagnosis are not eligible

Women diagnosed with osteoporosis may participate in this trial provided they are receiving appropriate therapy or if they have declined therapy

Absolute neutrophil count (ANC) >= 1,000/uL

Platelet count >= 100,000/uL

Measurable disease

Mammographic extent of calcifications must be accurately measurable in at least one dimension with each lesion >= 1 cm and =< 7 cm

DCIS must be visible on MRI based on central review

Patients with palpable DCIS or adenopathy are not eligible to participate

Patients with multifocal or bilateral disease are eligible

DCIS must express estrogen and/or progesterone receptor, as determined by immunohistochemical methods on the diagnostic pathology sample, according to the local institution’s standard protocol; greater than or equal to 1% cells will be considered to be positive

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Alliance for Clinical Trials in Oncology

  • National Cancer Institute
Eun-Sil (Shelley) Hwang, Principal Investigator

Trial Sites

U.S.A.

California
Los Angeles

Cedars-Sinai Medical Center

Armando Elario Giuliano
Ph: 310-423-8965

Armando Elario Giuliano
Principal Investigator

Oakland

Bay Area Tumor Institute

James Henry Feusner
Ph: 510-450-7600

James Henry Feusner
Principal Investigator

San Francisco

UCSF Medical Center-Mount Zion

Laura Jean Esserman
Ph: 877-827-3222

Laura Jean Esserman
Principal Investigator

Delaware
Newark

Christiana Care Health System-Christiana Hospital

Stephen Scott Grubbs
Ph: 302-733-6227

Stephen Scott Grubbs
Principal Investigator

Delaware Clinical and Laboratory Physicians PA

Stephen Scott Grubbs
Ph: 302-733-6227

Stephen Scott Grubbs
Principal Investigator

Helen F Graham Cancer Center

Stephen Scott Grubbs
Ph: 302-733-6227

Stephen Scott Grubbs
Principal Investigator

Medical Oncology Hematology Consultants PA

Stephen Scott Grubbs
Ph: 302-733-6227

Stephen Scott Grubbs
Principal Investigator

Regional Hematology and Oncology PA

Stephen Scott Grubbs
Ph: 302-733-6227

Stephen Scott Grubbs
Principal Investigator

Iowa
Iowa City

University of Iowa/Holden Comprehensive Cancer Center

Alexandra Thomas
Ph: 800-237-1225

Alexandra Thomas
Principal Investigator

Kentucky
Edgewood

Saint Elizabeth Medical Center South

Joseph Michael Guenther
Ph: 859-301-5473
Email: darla.hehman@stelizabeth.com

Joseph Michael Guenther
Principal Investigator

Fort Thomas

Saint Elizabeth Fort Thomas

Joseph Michael Guenther
Ph: 859-301-5473
Email: darla.hehman@stelizabeth.com

Joseph Michael Guenther
Principal Investigator

Lexington

Baptist Health Lexington

Peter Spalding Tate
Ph: 859-260-6425

Peter Spalding Tate
Principal Investigator

Maryland
Randallstown

Northwest Hospital Center

Mayer Gorbaty
Ph: 410-601-6120
Email: pridgely@lifebridgehealth.org

Mayer Gorbaty
Principal Investigator

Massachusetts
Boston

Dana-Farber Cancer Institute

Mehra Golshan
Ph: 877-442-3324

Mehra Golshan
Principal Investigator

Dana-Farber Harvard Cancer Center

Mehra Golshan
Ph: 617-724-5200
Email: mgolshan@partners.org

Mehra Golshan
Principal Investigator

Michigan
Lansing

Sparrow Hospital

Christopher M. Reynolds
Ph: 734-712-4673

Christopher M. Reynolds
Principal Investigator

Minnesota
Rochester

Mayo Clinic

Tina J. Hieken
Ph: 507-538-7623

Tina J. Hieken
Principal Investigator

Missouri
Kansas City

Saint Luke's Hospital of Kansas City

Rakesh Gaur
Ph: 816-932-2677
Email: SLCIResearch1@saint-lukes.org

Rakesh Gaur
Principal Investigator

Saint Louis

Missouri Baptist Medical Center

Alan P. Lyss
Ph: 800-392-0936

Alan P. Lyss
Principal Investigator

North Carolina
Chapel Hill

University of North Carolina at Chapel Hill

David W. Ollila
Ph: 877-668-0683
Email: cancerclinicaltrials@med.unc.edu

David W. Ollila
Principal Investigator

Durham

Duke University Medical Center

Jeffrey Crawford
Ph: 888-275-3853

Jeffrey Crawford
Principal Investigator

Hendersonville

Margaret R Pardee Memorial Hospital

James Earl Radford
Ph: 828-696-4716

James Earl Radford
Principal Investigator

Ohio
Columbus

Grant Medical Center

John Philip Kuebler
Ph: 614-566-3275

John Philip Kuebler
Principal Investigator

Ohio State University Comprehensive Cancer Center

Lisa Diane Yee
Ph: 800-293-5066
Email: Jamesline@osumc.edu

Lisa Diane Yee
Principal Investigator

Riverside Methodist Hospital

John Philip Kuebler
Ph: 614-566-3275

John Philip Kuebler
Principal Investigator

Portsmouth

Southern Ohio Medical Center

John Philip Kuebler
Ph: 614-566-3275

John Philip Kuebler
Principal Investigator

Oklahoma
Oklahoma City

University of Oklahoma Health Sciences Center

Wajeeha Razaq
Ph: 405-271-4272
Email: julie-traylor@ouhsc.edu

Wajeeha Razaq
Principal Investigator

South Carolina
Charleston

Medical University of South Carolina

Nancy DeMore
Ph: 843-792-9321

Nancy DeMore
Principal Investigator

Texas
Houston

M D Anderson Cancer Center

Isabelle Bedrosian
Ph: 713-792-3245

Isabelle Bedrosian
Principal Investigator

Virginia
Hampton

Sentara Cancer Institute at Sentara CarePlex Hospital

Richard A Hoefer
Ph: 757-827-2202

Richard A Hoefer
Principal Investigator

Norfolk

Sentara Hospitals

Richard A Hoefer
Ph: 757-827-2202

Richard A Hoefer
Principal Investigator

Sentara Leigh Hospital

Richard A Hoefer
Ph: 757-827-2202

Richard A Hoefer
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01439711

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.