Letrozole in Treating Postmenopausal Women With Ductal Carcinoma in Situ

This study is currently recruiting participants.
Verified December 2012 by National Cancer Institute (NCI)
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01439711
First received: September 21, 2011
Last updated: December 18, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: letrozole
Other: laboratory biomarker analysis
Other: questionnaire administration
Procedure: breast imaging study
Procedure: dynamic contrast-enhanced magnetic resonance imaging
Procedure: neoadjuvant therapy
Procedure: quality-of-life assessment
Procedure: therapeutic conventional surgery
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Neoadjuvant Letrozole for Postmenopausal Women With Estrogen Receptor Positive Ductal Carcinoma In SITU (DCIS)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 3-month and 6-month radiographic tumor volume [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Radiographic response of MRI-measured tumor at 3 months and 6 months [ Designated as safety issue: No ]
  • Radiographic response as measured by mammography at 3 months and 6 months [ Designated as safety issue: No ]
  • Type of primary surgery (mastectomy or lumpectomy) [ Designated as safety issue: No ]
  • Number of re-excisions required to obtain clear margins [ Designated as safety issue: No ]
  • Extent of residual DCIS post surgery [ Designated as safety issue: No ]
  • Presence of invasive cancer at surgery [ Designated as safety issue: No ]
  • Size of margins (smallest) at surgery [ Designated as safety issue: No ]
  • Treatment-related adverse events [ Designated as safety issue: Yes ]

Estimated Enrollment: 115
Study Start Date: February 2012
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • 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

  • 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.
  • To compare changes in MRI maximum lesion diameter and mammographic extent at baseline and following treatment.
  • To determine practice patterns of adjuvant hormonal and radiation therapy in patients who complete neoadjuvant letrozole therapy for DCIS.
  • 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.
  • To identify baseline IHC and expression biomarkers predictive of response to treatment, with response determined by extent of Ki67 reduction.
  • 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.
  • To assess quality-of-life and musculoskeletal symptoms associated with neoadjuvant letrozole for ER+ DCIS.

OUTLINE: This is a multicenter study.

Patients receive neoadjuvant letrozole orally (PO) once daily (QD) for 3 months. Patients then undergo MRI with an IV contrast. Patients with progressive disease discontinue letrozole and undergo surgery. Patients with complete, partial, or stable disease continue letrozole PO QD for an additional 3 months before undergoing another MRI and surgery. Patients continue receiving letrozole until the day before surgery.

Surgery (mastectomy or lumpectomy) must be performed within 30 days of the 3- or 6-month MRI.

Patients' core biopsy specimen and surgical excision specimen may be collected for correlative studies.

Patients may complete the Menopause Specific Quality-of-Life Questionnaire (MEMOQOL), the Brief Pain Inventory (BPI-SF), the Functional Assessment of Cancer Therapy - General (FACT-G), the Self-Efficacy for Coping with Side Effects, the Medication Taking Behavior (MMAS), and the Beliefs about Medicines Questionnaires at baseline and periodically during study.

After completion of study therapy, patients are followed up at 1, 3, and 6 months.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Pathologic confirmation of ductal carcinoma in situ (DCIS) without invasive cancer of the female breast 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
    • Disease stage Tis, N0, M0
    • All patients must have had a diagnostic core biopsy with clip placed at time of biopsy or prior to baseline MRI
  • Diagnostic tissue available for correlative studies
  • DCIS must express estrogen 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
  • Measurable disease

    • Mammographic extent of calcifications must be accurately measurable in at least one dimension with each lesion ≥ 1 cm and ≤ 5 cm
    • DCIS must be visible on MRI without radiographic evidence of invasive cancer
    • Patients with palpable DCIS or adenopathy are not eligible to participate

PATIENT CHARACTERISTICS:

  • 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) NOTE: *The use of GnRH analogs to achieve postmenopausal status is not allowed.
  • ECOG performance status 0 or 1
  • ANC ≥ 1,000/μL
  • Platelet count ≥ 100,000/μL
  • Serum creatinine ≤ 1.7 mg/dL
  • Bilirubin ≤ 2.0 mg/dL
  • AST/ALT ≤ 2.5 times upper limit of normal
  • Serum estradiol level assay < 20 pg/mL

    • Required for patients < 55 years of age and one year or more of amenorrhea
  • Not pregnant or nursing
  • No contraindications to breast MRI
  • Women diagnosed with osteoporosis may participate in this trial provided they are receiving appropriate therapy

PRIOR CONCURRENT THERAPY:

  • No prior surgical excision in the index breast for ductal carcinoma in situ (DCIS) or invasive cancer
  • Any exogenous hormone therapy must be completed 4 weeks prior to registration
  • Any patients with a history of tamoxifen or raloxifene use will be excluded
  • No prior neoadjuvant/adjuvant therapy for breast cancer
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01439711

Locations
United States, Arizona
Mayo Clinic Scottsdale Recruiting
Scottsdale, Arizona, United States, 85259-5499
Contact: Clinical Trials Office - All Mayo Clinic Locations    507-538-7623      
United States, California
CCOP - Bay Area Tumor Institute Recruiting
Oakland, California, United States, 94609
Contact: James H. Feusner, MD    510-428-3689      
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94115
Contact: Clinical Trials Office - UCSF Helen Diller Family Comprehensi    877-827-3222      
United States, Kentucky
St. Elizabeth Medical Center Recruiting
Edgewood, Kentucky, United States, 41017
Contact: Clinical Trials Office - St. Elizabeth Medical Center    859-301-2237      
United States, Minnesota
Mayo Clinic Cancer Center Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Office - All Mayo Clinic Locations    507-538-7623      
United States, Missouri
Missouri Baptist Cancer Center Recruiting
Saint Louis, Missouri, United States, 63131
Contact: Alan P. Lyss, MD    314-996-5514      
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599-7295
Contact: Clinical Trials Office - Lineberger Comprehensive Cancer Cente    877-668-0683; 919-966-4432      
Duke Cancer Institute Recruiting
Durham, North Carolina, United States, 27710
Contact: Clinical Trials Office - Duke Cancer Institute    888-275-3853      
Pardee Memorial Hospital Recruiting
Hendersonville, North Carolina, United States, 28791
Contact: James E. Radford, MD    828-692-8045      
United States, Ohio
Bethesda North Hospital Recruiting
Cincinnati, Ohio, United States, 45242
Contact: Ching Ho    513-745-1111      
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210-1240
Contact: Ohio State University Cancer Clinical Trial Matching Service    866-627-7616    Jamesline@osumc.edu   
United States, Texas
M. D. Anderson Cancer Center at University of Texas Recruiting
Houston, Texas, United States, 77030-4009
Contact: Clinical Trials Office - M. D. Anderson Cancer Center at the U    713-792-3245      
Sponsors and Collaborators
Cancer and Leukemia Group B
Investigators
Principal Investigator: E. Shelley Hwang, MD, MPH Duke University
  More Information

Additional Information:
No publications provided

Responsible Party: Richard L. Schilsky, Cancer and Leukemia Group B
ClinicalTrials.gov Identifier: NCT01439711     History of Changes
Other Study ID Numbers: CDR0000701992, CALGB-40903
Study First Received: September 21, 2011
Last Updated: December 18, 2012
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
ductal breast carcinoma in situ
estrogen receptor-positive breast cancer

Additional relevant MeSH terms:
Carcinoma, Ductal, Breast
Breast Neoplasms
Carcinoma
Carcinoma in Situ
Carcinoma, Intraductal, Noninfiltrating
Carcinoma, Ductal
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Estrogens
Letrozole
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 16, 2014