Letrozole in Treating Postmenopausal Women With Ductal Carcinoma in Situ
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT01439711
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- 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.
- Detailed Description
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. These are two additional radiographic parameters which may also biological response to therapy.
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. Subsets showing the greatest reduction in Ki67 would be the most likely candidates for non-operative treatment in future studies.
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 positive DCIS.
Patients will be followed up to 6 months post-surgery.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 108
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description letrozole + MRI + surgery conventional surgery 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. letrozole + MRI + surgery letrozole 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. letrozole + MRI + surgery MRI 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.
- Primary Outcome Measures
Name Time Method Mean Total MRI Functional Tumor Volume (FTV) Change From Baseline to Month 3 (V3) up to 3 months from start of treatment 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.
Mean Total MRI Functional Tumor Volume (FTV) Change From Baseline to Month 6 (V6) up to 6 months from start of treatment 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.
- Secondary Outcome Measures
Name Time Method Mean Total MRI Tumor Diameter Change From Baseline to Month 3 3-months To ascertain the change in maximum tumor diameter from baseline to 3 months (D3) the same methods as in Primary outcome #1 will be used but on diameter instead of volume. For patients with more than one lesion longest diameter measurement, the sum of all lesion longest diameter measurements was calculated.
Change in Maximum Diameter at 6-months Based on Mammographic Measurement (MD6) 6-months Change in maximum diameter at 6-months based on mammographic measurement (MD6) will be estimated using the methods in Primary Outcome #1, but using the mammographic measurements instead.
Type of Primary Surgery (Mastectomy or Lumpectomy) up to 6 months Rate of Mastectomy will be estimated as the number of mastectomies divided by the number of surgeries. A 95% confidence interval will be constructed using exact binomial methods. Rate of Lumpectomy will be estimated as the number of lumpectomies divided by the number of surgeries. A 95% confidence interval will be constructed using exact binomial methods.
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 Presence of Invasive Cancer at Surgery 3-months and 6-months Size of Margins (Smallest) at Surgery 3-months and 6-months Incidence of Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Up to 6 months post surgery The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. The percentage of patients with a maximum grade 3 or higher adverse event at least possibly related to the study treatment are reported below.
Mean Total MRI Tumor Diameter Change From Baseline to Month 6 6 months To ascertain the change in maximum tumor diameter from baseline to 6 months (D6) the same methods as in Primary outcome #2 will be used but on diameter instead of volume. For patients with more than one lesion longest diameter measurement, the sum of all lesion longest diameter measurements was calculated.
Trial Locations
- Locations (32)
Southern Ohio Medical Center
🇺🇸Portsmouth, Ohio, United States
Missouri Baptist Medical Center
🇺🇸Saint Louis, Missouri, United States
Bay Area Tumor Institute
🇺🇸Oakland, California, United States
Delaware Clinical and Laboratory Physicians PA
🇺🇸Newark, Delaware, United States
Helen F Graham Cancer Center
🇺🇸Newark, Delaware, United States
Medical Oncology Hematology Consultants PA
🇺🇸Newark, Delaware, United States
Regional Hematology and Oncology PA
🇺🇸Newark, Delaware, United States
Christiana Care Health System-Christiana Hospital
🇺🇸Newark, Delaware, United States
Saint Elizabeth Medical Center South
🇺🇸Edgewood, Kentucky, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
Sentara Hospitals
🇺🇸Norfolk, Virginia, United States
Saint Elizabeth Fort Thomas
🇺🇸Fort Thomas, Kentucky, United States
Sentara Cancer Institute at Sentara CarePlex Hospital
🇺🇸Hampton, Virginia, United States
Sentara Leigh Hospital
🇺🇸Norfolk, Virginia, United States
Margaret R Pardee Memorial Hospital
🇺🇸Hendersonville, North Carolina, United States
Exempla Saint Joseph Hospital
🇺🇸Denver, Colorado, United States
Baptist Health Lexington
🇺🇸Lexington, Kentucky, United States
Saint Luke's Hospital of Kansas City
🇺🇸Kansas City, Missouri, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
UCSF Medical Center-Mount Zion
🇺🇸San Francisco, California, United States
Northwest Hospital Center
🇺🇸Randallstown, Maryland, United States
Sparrow Hospital
🇺🇸Lansing, Michigan, United States
Riverside Methodist Hospital
🇺🇸Columbus, Ohio, United States
Grant Medical Center
🇺🇸Columbus, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
M. D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States