Endocrine Response in Women With Invasive Lobular Breast Cancer

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2014 by University of Pittsburgh
Sponsor:
Information provided by (Responsible Party):
Rachel Jankowitz, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT02206984
First received: July 30, 2014
Last updated: NA
Last verified: July 2014
History: No changes posted
  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
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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 University of Pittsburgh:

Primary Outcome Measures:
  • Ki67 proliferative index [ Time Frame: Day 21 compared to baseline ] [ Designated as safety issue: No ]
    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: October 2014
Estimated Primary Completion Date: October 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

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed invasive lobular breast cancer (excluding pleomorphic and HER-2 positive lobular cancer), measuring at least 1 centimeter (cm) radiographically or clinically, clinical stages I-III. (Note: See Appendix A for staging criteria.) 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.
  • Invasive lobular carcinoma of pleomorphic subtype.
  • HER-2 positivity.
  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.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Rachel Jankowitz, M.D., University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02206984     History of Changes
Other Study ID Numbers: ILC
Study First Received: July 30, 2014
Last Updated: July 30, 2014
Health Authority: United States: Data and Safety Monitoring Board
United States: Institutional Review Board
United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 16, 2014