Letrozole in Treating Postmenopausal Women With Ductal Carcinoma in Situ

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT01439711
First received: September 21, 2011
Last updated: June 20, 2016
Last verified: June 2016
  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
Procedure: MRI
Procedure: conventional surgery
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
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 Alliance for Clinical Trials in Oncology:

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

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

Estimated Enrollment: 115
Study Start Date: February 2012
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: letrozole + MRI + 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.
Drug: letrozole Procedure: MRI Procedure: conventional surgery

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01439711

  Hide Study Locations
Locations
United States, California
Cedars Sinai Medical Center
Los Angeles, California, United States, 90048
Bay Area Tumor Institute
Oakland, California, United States, 94609
UCSF Medical Center-Mount Zion
San Francisco, California, United States, 94115
United States, Colorado
Exempla Saint Joseph Hospital
Denver, Colorado, United States, 80218
United States, Delaware
Delaware Clinical and Laboratory Physicians PA
Newark, Delaware, United States, 19713
Helen F Graham Cancer Center
Newark, Delaware, United States, 19713
Medical Oncology Hematology Consultants PA
Newark, Delaware, United States, 19713
Regional Hematology and Oncology PA
Newark, Delaware, United States, 19713
Christiana Care Health System-Christiana Hospital
Newark, Delaware, United States, 19718
United States, Iowa
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States, 52242
United States, Kentucky
Saint Elizabeth Medical Center South
Edgewood, Kentucky, United States, 41017
Saint Elizabeth Fort Thomas
Fort Thomas, Kentucky, United States, 41075
Baptist Health Lexington
Lexington, Kentucky, United States, 40503
United States, Maryland
Northwest Hospital Center
Randallstown, Maryland, United States, 21133
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
Sparrow Hospital
Lansing, Michigan, United States, 48912
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Missouri
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, United States, 64111
Missouri Baptist Medical Center
Saint Louis, Missouri, United States, 63131
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Duke University Medical Center
Durham, North Carolina, United States, 27710
Margaret R Pardee Memorial Hospital
Hendersonville, North Carolina, United States, 28791
United States, Ohio
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
Riverside Methodist Hospital
Columbus, Ohio, United States, 43214
Grant Medical Center
Columbus, Ohio, United States, 43215
Southern Ohio Medical Center
Portsmouth, Ohio, United States, 45662
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
M. D. Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Virginia
Sentara Cancer Institute at Sentara CarePlex Hospital
Hampton, Virginia, United States, 23666
Sentara Leigh Hospital
Norfolk, Virginia, United States, 23502
Sentara Hospitals
Norfolk, Virginia, United States, 23507
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Study Chair: Shelley Hwang, MD, MPH Duke University
  More Information

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT01439711     History of Changes
Other Study ID Numbers: CALGB-40903  CDR0000701992  U10CA037447  NCI-2011-03452 
Study First Received: September 21, 2011
Last Updated: June 20, 2016
Health Authority: United States: NCI Central Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Alliance for Clinical Trials in Oncology:
ductal breast carcinoma in situ
estrogen receptor-positive breast cancer

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

ClinicalTrials.gov processed this record on August 25, 2016