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

September 21, 2011
December 18, 2012
February 2012
June 2014   (final data collection date for primary outcome measure)
3-month and 6-month radiographic tumor volume [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01439711 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Letrozole in Treating Postmenopausal Women With Ductal Carcinoma in Situ
Phase II Study of Neoadjuvant Letrozole for Postmenopausal Women With Estrogen Receptor Positive Ductal Carcinoma In SITU (DCIS)

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.

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.

Interventional
Phase 2
Masking: Open Label
Primary Purpose: Treatment
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
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
115
Not Provided
June 2014   (final data collection date for primary outcome measure)

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
Female
18 Years and older
No
Not Provided
United States
 
NCT01439711
CDR0000701992, CALGB-40903
Not Provided
Richard L. Schilsky, Cancer and Leukemia Group B
Cancer and Leukemia Group B
National Cancer Institute (NCI)
Principal Investigator: E. Shelley Hwang, MD, MPH Duke University
National Cancer Institute (NCI)
December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP