Clinical Trials /

Endocrine Response in Women With Invasive Lobular Breast Cancer

NCT02206984

Description:

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).

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Endocrine Response in Women With Invasive Lobular <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

Title

  • Brief Title: Endocrine Response in Women With Invasive Lobular Breast Cancer
  • Official Title: A Trial of Endocrine Response in Women With Invasive Lobular Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02206984

    ORG ID: ILC

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Tamoxifen tamoxifen
    Anastrozole Anastrozole
    Fulvestrant fulvestrant

    Trial 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).

    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.

    Trial Arms

    Name Type Description Interventions
    tamoxifen Active Comparator Tamoxifen is administered orally, at a dose of 20 mg,daily, for 21 days Tamoxifen
    Anastrozole Active Comparator 1mg given orally daily for 21 days Anastrozole
    fulvestrant Active Comparator 500 mg, administered as two 250 mg IM injections, given on days 1 and 14 Fulvestrant

    Eligibility 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.

    Minimum Eligible Age: N/A

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Ki67 proliferative index

    Secondary Outcome Measures

    Trial Keywords