Letrozole in Treating Postmenopausal Women With Ductal Carcinoma in Situ

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIBiomarker/Laboratory analysis, Diagnostic, TreatmentActive18 and overNCI, OtherCALGB-40903
CDR0000701992, U10CA037447, NCI-2011-03452, NCT01439711

Trial Description

Summary

RATIONALE: 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.

PURPOSE: This phase II trial is studying how well letrozole works in treating women with ductal carcinoma in situ.

Further Study Information

Treatment with letrozole begins within 21 days of registration, and only after notification has been received from the UCSF Breast MRI Research Laboratory that the baseline MRI is acceptable. Protocol therapy will consist of 6 months of letrozole, administered orally at a dose of 2.5 mg/day. Patients will have a MRI for disease evaluation at months 3 and 6. All patients will continue to take study drug until the day prior to surgery, whether at month 3 or at month 6 or may stop if they experience unacceptable toxicity. It is expected that decisions regarding any adjuvant treatment (eg, radiation and hormonal therapy) will be made individually based on the best practice guidelines, using informed and shared decision making between patient and provider. The primary and secondary objectives are provided below.

Primary objective:

1. To estimate the mean change in 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:

1. 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.

2. To compare changes in MRI maximum lesion diameter and mammographic extent at baseline and following treatment.

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

4. 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.

5. To identify baseline IHC and expression biomarkers predictive of response to treatment, with response determined by extent of Ki67 reduction.

6. 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.

7. To assess quality-of-life and musculoskeletal symptoms associated with neoadjuvant letrozole for ER+ DCIS.

Patients will be followed up to 6 months post-surgery.

Eligibility Criteria

Eligibility Criteria:

1. Histologic documentation: Pathologic confirmation of ductal carcinoma in situ (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.

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

2. 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.

2. Tissue samples: Patient has diagnostic tissue available for correlative studies.

3. Clinical stage: Tis or Tlmi N0, M0

4. Hormone receptor status: 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.

5. Menopausal status: Patients must be postmenopausal defined as:

1. Age ≥ 55 years and one year or more of amenorrhea

2. Age < 55 years and one year or more amenorrhea, with an estradiol assay < 20pg/ml

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

The use of GnRH analogs to achieve post menopausal status is not allowed.

6. Prior treatment:

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

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

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

4. No prior neoadjuvant/adjuvant therapy for current DCIS diagnosis

7. Contraindication to MRI: No contraindications to breast MRI

8. Measurable disease: Mammographic extent of calcifications must be accurately measurable in at least one dimension with each lesion ≥ 1 cm and ≤ 7 cm

1. DCIS must be visible on MRI based on central review.

2. Patients with palpable DCIS or adenopathy are not eligible to participate.

3. Patients with multifocal or bilateral disease are eligible.

9. History of osteoporosis: Women diagnosed with osteoporosis may participate in this trial provided they are receiving appropriate therapy or if they have declined therapy.

10. Age: Patients ≥ 18 years of age

11. Performance Status: ECOG performance status 0 or 1

12. Pregnancy/nursing status: Not pregnant or nursing

13. Required Initial Laboratory Values:

1. ANC ≥ 1,000/μL

2. Platelet count ≥ 100,000/μL

3. Serum creatinine ≤ 1.7 mg/dL

4. Bilirubin ≤ 2.0 mg/dL

5. AST/ALT ≤ 2.5 times upper limit of normal

6. Serum estradiol level assay < 20 pg/mL

  • Required for patients < 55 years of age and one year or more of amenorrhea

Trial Contact Information

Trial Lead Organizations/Sponsors

Alliance for Clinical Trials in Oncology

  • National Cancer Institute
E. Shelley Hwang, Principal Investigator

Trial Sites

U.S.A.

Alabama
Mobile

Southern Cancer Center PC-Providence

Brian J Heller
Ph: 888-625-6896

California
Los Angeles

Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center

Armando E Giuliano
Ph: 310-423-8965

Oakland

CCOP - Bay Area Tumor Institute

James H. Feusner
Ph: 510-450-7600

San Francisco

UCSF Helen Diller Family Comprehensive Cancer Center

Laura J. Esserman
Ph: 877-827-3222

Colorado
Denver

St. Joseph Hospital

Keren Sturtz
Ph: 888-785-6789

Delaware
Newark

Delaware Clinical and Laboratory Physicians

Stephen Scott Grubbs
Ph: 302-733-6227

Helen F. Graham Cancer Center at Christiana Hospital

Stephen Scott Grubbs
Ph: 302-733-6227

Stephen Scott Grubbs
Ph: 302-733-6227

Medical Oncology Hematology Consultants, PA at Helen F. Graham Cancer Center

Stephen Scott Grubbs
Ph: 302-733-6227

Regional Hematology/Oncology, PA - Newark

Stephen Scott Grubbs
Ph: 302-733-6227

Iowa
Iowa City

Holden Comprehensive Cancer Center at University of Iowa

Alexandra Thomas
Ph: 800-237-1225

Kentucky
Edgewood

St. Elizabeth Medical Center

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

Fort Thomas

St. Luke Hospital East

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

Lexington

Central Baptist Hospital

Peter S. Tate
Ph: 859-260-6425

Maryland
Randallstown

Northwest Hospital Center

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

Massachusetts
Boston

Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute

Mehra Golshan
Ph: 617-724-5200

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

Minnesota
Rochester

Mayo Clinic Cancer Center

Tina J Hieken
Ph: 507-538-7623

Missouri
Kansas City

Saint Luke's Hospital

Rakesh Gaur
Ph: 913-948-5588
Email: aroland@kccop.org

Saint Louis

Missouri Baptist Cancer Center

Alan Philip Lyss
Ph: 800-392-0936

North Carolina
Chapel Hill

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

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

Durham

Duke Cancer Institute

Jeffrey Crawford
Ph: 888-275-3853

Hendersonville

Comprehensive Cancer Center at Pardee Hospital

James E. Radford
Ph: 828-696-4716

Ohio
Columbus

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

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

Grant Medical Center Cancer Care

J. Philip Kuebler
Ph: 614-566-3275

Riverside Methodist Hospital Cancer Care

J. Philip Kuebler
Ph: 614-566-3275

Portsmouth

Southern Ohio Medical Center Cancer Center

J. Philip Kuebler
Ph: 614-566-3275

Oklahoma
Oklahoma City

Stephenson Cancer Center at the University of Oklahoma

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

Texas
Dallas

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Ann Marilyn Leitch
Ph: 214-648-7097

Houston

Univeristy of Texas M.D. Anderson Cancer Center

Isabelle Bedrosian
Ph: 713-792-3245

Virginia
Hampton

Sentara Cancer Institute at Sentara CarePlex Hospital

Richard A Hoefer
Ph: 757-827-2202

Norfolk

Sentara Cancer Institute at Sentara Norfolk General Hospital

Richard A Hoefer
Ph: 757-827-2202

Sentara Leigh Hospital

Richard A Hoefer
Ph: 757-827-2202

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01439711
ClinicalTrials.gov processed this data on April 09, 2015

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.