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Endocrine Response in Women With Invasive Lobular Breast Cancer

This study is currently recruiting participants.
Verified November 2017 by Rachel Jankowitz, University of Pittsburgh
Sponsor:
ClinicalTrials.gov Identifier:
NCT02206984
First Posted: August 1, 2014
Last Update Posted: November 21, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Rachel Jankowitz, University of Pittsburgh
  Purpose

RATIONALE: Currently, adjuvant endocrine therapy often follows a "one-size-fits- all" approach, with most premenopausal women receiving tamoxifen, and most postmenopausal receiving aromatase inhibitor therapy. In current clinical practice, patients with invasive lobular carcinoma are treated no differently than patients with invasive ductal carcinoma based on the void of information specific to patients with this tumor type. Identification of a biological signal of tamoxifen and/or AI-resistance and/or fulvestrant-sensitivity in ILC patients would have dramatic implications for the future management of this breast cancer subtype.

PURPOSE: To study whether fulvestrant is more effective than anastrozole or tamoxifen in reducing Ki67 in ILC and whether that Ki67 reduction will correlate with alterations in expression of ER and ER-regulated genes. Differential Ki67 effect in this study will serve as a surrogate for outcome of ILC patients on endocrine therapy.

Primary Objective:

To determine the change from baseline to post-treatment Ki67 values in ER-positive, HER2-negative ILC tissue derived from postmenopausal women awaiting definitive surgery or further neoadjuvant treatment who are randomized to 21-24 days of neoadjuvant endocrine treatments with fulvestrant (two 250 mg IM injections given on day 1), anastrozole (1mg given orally daily), or tamoxifen (20mg given orally daily).


Condition Intervention
Breast Cancer Drug: Tamoxifen Drug: Anastrozole Drug: Fulvestrant

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Trial of Endocrine Response in Women With Invasive Lobular Breast Cancer

Resource links provided by NLM:


Further study details as provided by Rachel Jankowitz, University of Pittsburgh:

Primary Outcome Measures:
  • Ki67 proliferative index [ Time Frame: Day 21 compared to baseline ]
    Ki67 proliferative index is measured as the percent of positively staining cells. Given the log-normal distribution of the Ki67 measurements generally observed in this population[59], values will be log-transformed for statistical analysis. Therefore, the primary endpoint of the change in Ki67 at Day 21 compared to baseline is given by log(Ki67Day 21/Ki67BL). For descriptive purposes, summary statistics and corresponding 95% confidence intervals for BL, Day 21 and percent change from baseline will be reported within study arm on the original scale.


Estimated Enrollment: 150
Study Start Date: August 2015
Estimated Study Completion Date: October 2020
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: tamoxifen
Tamoxifen is administered orally, at a dose of 20 mg,daily, for 21 days
Drug: Tamoxifen
Active Comparator: Anastrozole
1mg given orally daily for 21 days
Drug: Anastrozole
Active Comparator: fulvestrant
500 mg, administered as two 250 mg IM injections, given on days 1 and 14
Drug: Fulvestrant

Detailed Description:

OBJECTIVES

Primary

To determine the change from baseline to post-treatment Ki67 values in ER-positive, HER2-negative ILC tissue derived from postmenopausal women awaiting definitive surgery or further neoadjuvant treatment who are randomized to 21-24 days of neoadjuvant endocrine treatments with fulvestrant (two 250 mg IM injections given on day 1), anastrozole (1mg given orally daily), or tamoxifen (20mg given orally daily).

Secondary

  • To evaluate ER protein expression in ILC tissues at baseline and following neoadjuvant endocrine therapy.
  • To evaluate PR protein expression in ILC tissues at baseline and following neo-adjuvant endocrine therapy.
  • To evaluate ER-related and ILC-specific candidate gene mRNA expression in ILC tissues at baseline and following neoadjuvant endocrine therapy in an effort to identify biomarkers of endocrine response and putative drivers of endocrine resistance in ILC.
  • To evaluate associations between changes in Ki67 in ILC tissues following neoadjuvant endocrine therapy with ER and PR protein expression, or ER and candidate gene mRNA expression at baseline and post-treatment.

Exploratory

  • To evaluate DNA methylation in ILC tissues at baseline and following neo-adjuvant endocrine therapy.
  • To evaluate associations between germline and somatic DNA sequence variants with changes in Ki67 in ILC tissues following neo-adjuvant endocrine therapy.
  • To evaluate the activity of signaling pathways in ILC tissues by immunohistochemical or other protein analyses, such as histone modifications, at baseline and following neo-adjuvant endocrine therapy.
  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed invasive lobular breast cancer that is hormone receptor-positive and HER2-negative, measuring at least 1 centimeter (cm) radiographically or clinically, clinical stages I-III. Invasive lobular histology will be diagnosed at the enrolling institution for purposes of study participation. Subsequently, invasive lobular histology will be confirmed by central pathology review, but this central review will not be required prior to patient enrollment.
  • Prior to initiation of study agents, study participants must agree to both a baseline research core biopsy, and if definitive surgery is not performed at day 21-24 after treatment, a second post-treatment research core biopsy. For patients undergoing surgery, the second biopsy will be removed from tissue excised during their operation.
  • Hormone receptor (HR) status of the invasive component must be documented on the diagnostic core biopsy before trial enrollment. The tumor must be ER-positive. ER will be considered positive if staining is 1% or greater. This will be determined at the enrolling institution for purposes of study participation and enrollment onto the trial. Subsequently, HR status will be confirmed by central pathology review, but this central review will not be required prior to enrolling the patient.
  • Patients must be female
  • Participants must be fully postmenopausal
  • ECOG performance status of 0, 1 or 2
  • Adequate organ and marrow function as defined below:

    • leukocytes >3,000/mm3
    • absolute neutrophil count >1,500/mm3
    • platelets >100,000/mm3
    • total bilirubin within normal laboratory limits
    • AST(SGOT)/ALT(SGPT) <2.5 times the laboratory upper limit of normal
    • creatinine within normal laboratory limits
  • Prior use of hormone contraceptives and replacement therapy is allowed (e.g., estrogen and/or progestin), but must have been discontinued at least 30 days prior to the diagnostic biopsy. Vaginal preparations (e.g., Vagifem® or Estring®) are allowed.
  • Participant must be aware of the nature of her malignancy, understand the study requirements and risks and be able and willing to sign a written informed consent document.

Exclusion Criteria:

  • Prior or concurrent use of hormonal therapy, chemotherapy, radiation therapy, or novel therapy to treat the current breast cancer, including any history of prior irradiation to the ipsilateral breast.
  • Concurrent use of any other investigational agents.
  • History of allergic reactions/hypersensitivity attributed to compounds of similar chemical or biologic composition to tamoxifen, anastrozole, or fulvestrant or any of their ingredients.
  • History of thromboembolic disease or uterine cancer that is considered a contraindication to tamoxifen.
  • Active hepatitis viral infections.
  • Uncontrolled current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • HER-2 positivity.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02206984


Contacts
Contact: Brenda L Steele, BSN, RN 412-641-3418 Steebx@upmc.edu
Contact: Rometa R Pollard, BS 412-641-5430 pollardrr@upmc.edu

Locations
United States, Alabama
UAB Comprehensive Cancer Center Recruiting
Birmingham, Alabama, United States, 35294
Contact: Erica M Reasor-Stringer, MD    205-934-3411    strinem@uab.edu   
Contact: Liz Busby, RN, BSN    205-934-0337    lizbusby@uab.edu   
United States, Indiana
IU Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Anna M Storniolo, MD    312-278-7576    astornio@iu.edu   
Contact: Tammi Detty, CCRP    (317)278-6227    tmdetty@iupui.edu   
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Tina Hieken, MD    855-776-0015    Hieken.Tina@mayo.edu   
Contact: Kim Hitchcock    507-266-3867    hitchcock.kim@mayo.edu   
United States, New York
ALBERT EINSTEIN COLLEGE OF MEDICINE Montefiore Medical Center Recruiting
Bronx, New York, United States, 10467
Contact: Joseph Sparano, MD    718-405-8404    JSPARANO@montefiore.org   
Contact: Vilma Calderon, RN       VCALDERO@montefiore.org   
United States, North Carolina
University of North Carolina at Chapel Hill Not yet recruiting
Chapel Hill, North Carolina, United States, 27514
Contact: Kandice McGuire, MD    919-966-5221    kandace_mcguire@med.unc.edu   
Contact: Rachel Phipps, RN         
United States, Pennsylvania
Magee Womens Hospital of UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Brenda L Steele, BSN, RN    412-641-3418    Steebx@upmc.edu   
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77064
Contact: Alastair Thompson, MD    713-745-2792    athompson1@mdanderson.org   
Contact: Jaime Crow, MS    717-792-6443    jrcrow@mdanderson.org   
United States, Washington
Univ. of Washington, Seattle Cancer Care Alliance, Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States, 98109
Contact: Hannah Linden, MD    206-288-1234    hmlinden@seattlecca.org   
Contact: Obsy Tadesse    206-288-6831    otadesse@seattlecca.org   
Sponsors and Collaborators
Rachel Jankowitz
  More Information

Responsible Party: Rachel Jankowitz, M.D., University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02206984     History of Changes
Other Study ID Numbers: 13-164 (ILC)
First Submitted: July 30, 2014
First Posted: August 1, 2014
Last Update Posted: November 21, 2017
Last Verified: November 2017

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Fulvestrant
Anastrozole
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents
Estrogen Receptor Antagonists
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action