Entinostat and Anastrozole in Treating Postmenopausal Women With TNBC That Can Be Removed by Surgery

NCT01234532 | Terminated Phase 2 Results

• 4 other identifiers: HP-00047658NCI-2011-02542CDR00006875078597
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial is studying how well giving entinostat and anastrozole together works in treating postmenopausal women with triple-negative breast cancer that can be removed by surgery. Entinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Hormone therapy using anastrozole may fight breast cancer by blocking the use of estrogen by the tumor cells. Giving entinostat together with anastrozole may be an effective treatment for breast cancer.

Conditions

Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Progesterone Receptor-negative Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Triple-negative Breast Cancer

Outcome Measures

Primary Outcomes (4)

• Recommended Phase II Dose of Entinostat in Combination With Anastrozole (Pilot)

  Since the study was terminated early there was insufficient data for analysis and to recommend a phase II dose of entinostat in combination with anastrozole

  Duration of the study is 29 days followed by 30 days end of study assessment visit, up to 59 days

• Number of Participants With Adverse Events

  To address the safety of the regimen, a maximum width 90% confidence interval for any grade 3 or higher toxicity will be approximately 30%. For 5 patients in this study, if the true unknown probability of a rare toxicity is 10%, the probability of observing 1 or more toxicities is 97%, and if the true toxicity rate is 5% then the probability of observing one or more rare toxicities is 83%.

  Participants were followed during the study and for 30 days post treatment, up to 59 days

• Change in Proliferative Index (Ki67) (Phase II)

  The 95% confidence intervals will be constructed for the observed proportions. Exploratory data analysis and appropriate graphs will be used to decide whether data transformation (e.g. log or square-root) is necessary to assure an approximate normality. All descriptive statistics will be reported for ER and Ki67 expression. The general linear model approach and/or its non parametric alternative, the Wilcoxon test, will be used to assess whether there is any evidence of changes due to treatment.

  Baseline to the time of surgery, within 6 days after the last dose of entinostat, up to 35 days

• Change in Estrogen-receptor (ER) Expression (Phase II)

  The 95% confidence intervals will be constructed for the observed proportions. Exploratory data analysis and appropriate graphs will be used to decide whether data transformation (e.g. log or square-root) is necessary to assure an approximate normality. All descriptive statistics will be reported for ER and Ki67 expression. The general linear model approach and/or its non parametric alternative, the Wilcoxon test, will be used to assess whether there is any evidence of changes due to treatment.

  Baseline before the study treatment and at the time of surgery, up to 30 days

Secondary Outcomes (3)

• Clinical Response to Entinostat and Anastrozole

  Clinical response was assessed during the study treatment and before the surgery, up to 29 days

• Change in HER2

  Baseline before study treatment and at the time of surgery, up to 30 days

• The Pathological Response to Entinostat and Anastrozole

  Pathological response was assessed after the surgery, up to 59 days

Study Arms (1)

entinostat & anastrozole neoadjuvant

EXPERIMENTAL

Neoadjuvant entinostat daily on days 1, 8, 15, 22, and 29 + anastrozole daily on days 4-29 followed by surgery ie either lumpectomy or mastectomy. Correlative studies will be performed utilizing tissue and blood. A baseline tumor biopsy is done prior to study entry or archival tissue from diagnosis may be used and a representative tumor sample is submitted at time of surgery. Bloods are drawn for correlative sciences on day 1 and 15 of treatment prior to entinostat dosing and 30 mins post and again on day of surgery.

Drug: entinostat; Drug: anastrozole; Other: diagnostic laboratory biomarker analysis; Procedure: therapeutic conventional surgery

Interventions

entinostat DRUG

orally

Also known as: SNDX-275, MS-275

entinostat & anastrozole neoadjuvant

anastrozole DRUG

Given PO

Also known as: arimidex

entinostat & anastrozole neoadjuvant

diagnostic laboratory biomarker analysis OTHER

Correlative studies will be performed utilizing tissue and blood. A baseline tumor biopsy is done prior to study entry or archival tissue from diagnosis may be used and a representative tumor sample is submitted at time of surgery. Bloods are drawn for correlative sciences on day 1 and 15 of treatment prior to entinostat dosing and 30 mins post and again on day of surgery.

entinostat & anastrozole neoadjuvant

therapeutic conventional surgery PROCEDURE

Lumpectomy or mastectomy will be performed follwoing day 29 of study therapy

Also known as: Lumpectomy or mastectomy

entinostat & anastrozole neoadjuvant

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female greater than or equal to 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status \<2 (see Appendix A).
• Histologically confirmed adenocarcinoma of the breast.
• Evidence of hormone insensitivity (ER and PR negative) of primary tumor tissue. ER negative is define as ER 0 or \< 1% staining by immunohistochemistry. PR negativity is defined as PR \< 1% staining by immunohistochemistry.
• HER2 negative in the primary tumor tissue as defined by:
• Immunohistochemistry (IHC) Grade 0 as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within ≤10% of the invasive tumor cell
• IHC 1+ as defined by incomplete membrane staining that is faint/barely perceptible and within \>10% of the invasive tumor cell
• IHC Grade 2+ staining intensity by means of IHC analysis with no gene amplification below.
• No gene amplification on ISH based on
• Single-probe average HER2 copy number \<4.0 signals/cell
• Dual-probe HER2/CEP17 ratio \<2.0 with an average HER2 copy number \<4.0 signals/cell
• Ability to understand and the willingness to sign a written informed consent document.
• Patients must not have received any prior chemotherapy, radiation therapy, or endocrine therapy for their current breast cancer. Patients who received tamoxifen or raloxifene or another agent for prevention of breast cancer may be included as long as the patient has discontinued the treatment at least one month prior to baseline study biopsy.
• Women of childbearing potential must have negative (serum or urine) pregnancy test within 7 days prior to registration.
• Patients must have adequate tumor tissue sample prior to the enrolment available for correlative studies as defined below:

You may not qualify if:

• Patients may not be receiving any other investigational agents.
• Prior exposure to other HDAC inhibitors. However, prior valproic acid exposure is allowed providing
• ≥ 30 days wash-out period.
• History of allergic reactions or hypersensitivity to compounds of similar chemical or biologic composition to entinostat, benzamide, anastrozole, or tamoxifen.
• Any medical condition which in the opinion of the investigator puts the patient at risk of potentially serious complications while on this therapy. Examples: HIV, unstable angina, uncontrolled heart failure or hypertension, uncontrolled hyperlipidemia, uncontrolled diabetes mellitus, uncontrolled systemic infection.
• Previous or current systemic malignancy within the past 3 years other than breast cancer or adequately treated cervical carcinoma in situ or basal/squamous carcinoma of the skin.
• \- Women of all races and ethnic groups are eligible for this trial.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• Syndax Pharmaceuticals: collaborator

Study Sites (1)

University of Maryland Baltimore

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

entinostat; Anastrozole; Mastectomy, Segmental; Mastectomy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Surgical Procedures, Operative

Limitations and Caveats

Study was closed due to slow accrual and was not completed

Results Point of Contact

• Title: Katherine Tkaczuk, M.D.
• Organization: University of Maryland, Baltimore

ktkaczuk@umm.edu

410-328-2565

Study Officials

• Saranya Chumsri

  University of Chicago Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: no masking
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: no masking

Study Record Dates

• First Submitted: November 3, 2010
• First Posted: November 4, 2010
• Study Start: October 1, 2010
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: May 3, 2022
• Results First Posted: May 3, 2022

Record last verified: 2022-04

Locations

US (1)