Letrozole in Treating Postmenopausal Women With Ductal Carcinoma in Situ

NCT01439711 | Completed Phase 2 Results DMC

• 4 other identifiers: CALGB-40903CDR0000701992U10CA037447NCI-2011-03452
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 32

Brief 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.

Conditions

Breast Cancer

Keywords

ductal breast carcinoma in situ; estrogen receptor-positive breast cancer

Outcome Measures

Primary Outcomes (2)

• Mean Total MRI Functional Tumor Volume (FTV) Change From Baseline to Month 3 (V3)

  Mean total MRI FTV change from baseline to month 3 (V3): For patients with more than one measureable lesion on the MRI, the sum over all measureable lesions on the MRI was calculated at each time point. V3 was calculated by subtracting the total MRI FTV measured (i.e. the sum over all lesions present with MRI FTV measurements) at 3 months from the total MRI FTV measured at baseline. For V3 the raw change in the volume will be calculated for each patient and a mean and 95% confidence interval will be constructed using two-sided t-tests.

  up to 3 months from start of treatment

• Mean Total MRI Functional Tumor Volume (FTV) Change From Baseline to Month 6 (V6)

  Mean total MRI FTV change from baseline to month 6 (V6): For patients with more than one measureable lesion on the MRI, the sum over all measureable lesions on the MRI was calculated at each time point. V6 was calculated by subtracting the total MRI FTV measured at 6 months from the total MRI FTV measured at baseline. For V6 the raw change in the volume will be calculated for each patient and a mean and 95% confidence interval will be constructed using two-sided t-tests.

  up to 6 months from start of treatment

Secondary Outcomes (10)

• Mean Total MRI Tumor Diameter Change From Baseline to Month 3

  3-months

• Change in Maximum Diameter at 6-months Based on Mammographic Measurement (MD6)

  6-months

• Type of Primary Surgery (Mastectomy or Lumpectomy)

  up to 6 months

• Number of Re-excisions Required to Obtain Clear Margins

  3-months and 6-months

• Extent of Residual DCIS Post Surgery

  Up to 6 months post-surgery

Study Arms (1)

letrozole + MRI + surgery

EXPERIMENTAL

Patients receive letrozole (2.5 mg) one tablet each day after confirmation that the MRI is acceptable. There is a 3 and 6 month disease evaluation by MRI of both breasts. If the DCIS has grown, the patient will have surgery to remove it and will continue to take letrozole until the day before surgery. It is expected that decisions regarding any adjuvant treatment will be made individually based on best practice guidelines, using informed and shared decision making between the patient and provider.

Drug: letrozole; Procedure: MRI; Procedure: conventional surgery

Interventions

letrozole DRUG

letrozole + MRI + surgery

MRI PROCEDURE

letrozole + MRI + surgery

conventional surgery PROCEDURE

letrozole + MRI + surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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 T1mi 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator

Study Sites (32)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Bay Area Tumor Institute

Oakland, California, 94609, United States

Location

UCSF Medical Center-Mount Zion

San Francisco, California, 94115, United States

Location

Exempla Saint Joseph Hospital

Denver, Colorado, 80218, United States

Location

Delaware Clinical and Laboratory Physicians PA

Newark, Delaware, 19713, United States

Location

Helen F Graham Cancer Center

Newark, Delaware, 19713, United States

Location

Medical Oncology Hematology Consultants PA

Newark, Delaware, 19713, United States

Location

Regional Hematology and Oncology PA

Newark, Delaware, 19713, United States

Location

Christiana Care Health System-Christiana Hospital

Newark, Delaware, 19718, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Saint Elizabeth Medical Center South

Edgewood, Kentucky, 41017, United States

Location

Saint Elizabeth Fort Thomas

Fort Thomas, Kentucky, 41075, United States

Location

Baptist Health Lexington

Lexington, Kentucky, 40503, United States

Location

Northwest Hospital Center

Randallstown, Maryland, 21133, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Sparrow Hospital

Lansing, Michigan, 48912, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, 64111, United States

Location

Missouri Baptist Medical Center

St Louis, Missouri, 63131, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Margaret R Pardee Memorial Hospital

Hendersonville, North Carolina, 28791, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Riverside Methodist Hospital

Columbus, Ohio, 43214, United States

Location

Grant Medical Center

Columbus, Ohio, 43215, United States

Location

Southern Ohio Medical Center

Portsmouth, Ohio, 45662, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Sentara Cancer Institute at Sentara CarePlex Hospital

Hampton, Virginia, 23666, United States

Location

Sentara Leigh Hospital

Norfolk, Virginia, 23502, United States

Location

Sentara Hospitals

Norfolk, Virginia, 23507, United States

Location

Related Publications (2)

• Marks JR, Zhang D, Hardman T, Chen YY, Hall A, Simpson L, Hieken T, Bedrosian I, Price E, Sheng J, Dai Y, Lee M, Sibley AB, Owzar K, Hwang ES. Genomic alterations are associated with response to aromatase inhibitor therapy for ER-positive postmenopausal ductal carcinoma in situ: (CALGB 40903, Alliance). Breast Cancer Res. 2025 Feb 20;27(1):26. doi: 10.1186/s13058-025-01963-5.

  PMID: 39980051 DERIVED

• Hwang ES, Hyslop T, Hendrix LH, Duong S, Bedrosian I, Price E, Caudle A, Hieken T, Guenther J, Hudis CA, Winer E, Lyss AP, Dickson-Witmer D, Hoefer R, Ollila DW, Hardman T, Marks J, Chen YY, Krings G, Esserman L, Hylton N. Phase II Single-Arm Study of Preoperative Letrozole for Estrogen Receptor-Positive Postmenopausal Ductal Carcinoma In Situ: CALGB 40903 (Alliance). J Clin Oncol. 2020 Apr 20;38(12):1284-1292. doi: 10.1200/JCO.19.00510. Epub 2020 Mar 3.

  PMID: 32125937 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating

Interventions

Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Breast Carcinoma In Situ; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: E. Shelley Hwang MD MPH
• Organization: Duke University Medical Center

shelley.hwang@duke.edu

919-684-6849

Study Officials

• Shelley Hwang, MD, MPH

  Duke University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2011
• First Posted: September 23, 2011
• Study Start: February 1, 2012
• Primary Completion: August 1, 2016
• Study Completion: January 1, 2018
• Last Updated: March 27, 2018
• Results First Posted: March 27, 2018

Record last verified: 2018-02

Locations

US (32)