Phase II Study of Neoadjuvant Letrozole for Postmenopausal Women With Estrogen Receptor Positive Ductal Carcinoma In SITU (DCIS)
18 Years
N/A
Female
Breast Cancer
Trial Information
Phase II Study of Neoadjuvant Letrozole for Postmenopausal Women With Estrogen Receptor Positive Ductal Carcinoma In SITU (DCIS)
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
3-month and 6-month radiographic tumor volume
Safety Issue:
No
Principal Investigator
E. Shelley Hwang, MD, MPH
Investigator Role:
Principal Investigator
Investigator Affiliation:
Duke University
Authority:
Unspecified
Study ID:
CDR0000701992
NCT ID:
NCT01439711
Start Date:
February 2012
Completion Date:
Related Keywords:
- Breast Cancer
- ductal breast carcinoma in situ
- estrogen receptor-positive breast cancer
- Breast Neoplasms
- Carcinoma
- Carcinoma in Situ
- Carcinoma, Intraductal, Noninfiltrating
- Carcinoma, Ductal, Breast
- Carcinoma, Ductal
Name | Location |
|---|---|
| Mayo Clinic Scottsdale | Scottsdale, Arizona 85259 |
| Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
| CCOP - Bay Area Tumor Institute | Oakland, California 94609-3305 |
| Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill | Chapel Hill, North Carolina 27599-7570 |
| St. Elizabeth Medical Center | Edgewood, Kentucky 41017 |
| UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco, California 94115 |
| M. D. Anderson Cancer Center at University of Texas | Houston, Texas 77030-4009 |
| Missouri Baptist Cancer Center | St. Louis, Missouri 63131 |
| Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center | Columbus, Ohio 43210-1240 |
| Pardee Memorial Hospital | Hendersonville, North Carolina 28791 |
| Bethesda North Hospital | Cincinnati, Ohio 45242 |
| Duke Cancer Institute | Durham, North Carolina 27710 |
