Clinical Trials Directory

Trials / Terminated

TerminatedNCT01234532

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

GCC 0927 A Pilot and Phase II Study of Entinostat and Anastrozole/Tamoxifen in Women With Triple Negative Breast Cancer to Evaluate Biomarkers and Surrogates for Response

Status
Terminated
Phase
Phase 2
Study type
Interventional
Enrollment
5 (actual)
Sponsor
University of Maryland, Baltimore · Academic / Other
Sex
Female
Age
18 Years
Healthy volunteers
Not accepted

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.

Detailed description

PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of entinostat in combination with anastrozole or tamoxifen. (Pilot) II. To determine the optimal dose of entinostat in combination with anastrozole or tamoxifen for phase II. (Pilot) III. To determine baseline and percentage change in proliferative index (Ki67) before and after treatment with entinostat and anastrozole/tamoxifen in triple negative breast cancer (TNBC). (Phase II) IV. To determine the estrogen receptor (ER) expression after treatment with entinostat and anastrozole/tamoxifen in TNBC. (Phase II) SECONDARY OBJECTIVES: I. To evaluate baseline and change in the expression levels of progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), cytokeratin 5/6 (CK5/6), and aromatase before and after treatment with entinostat and anastrozole/tamoxifen. II. To assess baseline and change in tumor tissue histone H3 and H4 acetylation before and after treatment with entinostat and anastrozole/tamoxifen. III. To assess the clinical and pathological response to preoperative combination of entinostat and anastrozole/tamoxifen in TNBC. TERTIARY OBJECTIVES: I. To correlate the levels of histone H3 and H4 acetylation in tumors with the changes in Ki67 and ER. II. To evaluate baseline and change in gene methylation silencing and expression of candidate genes in tissues and in circulating DNA, including estrogen receptor (ER)-alpha, ER-beta, RAR-beta, cyclin D2, Twist, RASSF1A, and HIN-1. III. To correlate entinostat trough concentrations with histone H3 and H4 acetylation in tumors as well as the change in Ki67 and ER. IV. To evaluate baseline and change in the global gene expression profile before and after treatment with entinostat and anastrozole/tamoxifen. OUTLINE: This is a multicenter, pilot study followed by a phase II study. Patients receive entinostat orally (PO) once daily on days 1, 8, 15, 22, and 29 and anastrozole PO once daily on days 4-29. Patients then undergo mastectomy or lumpectomy. Tumor tissue samples are collected at baseline or from original diagnosis, and during surgery for correlative studies by IHC and RT-PCR. Blood samples are also collected at baseline, on days 1 and 15, and during surgery for correlative studies. After completion of study therapy, patients are followed up for 30 days.

Conditions

Interventions

TypeNameDescription
DRUGentinostatorally
DRUGanastrozoleGiven PO
OTHERdiagnostic laboratory biomarker analysisCorrelative 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.
PROCEDUREtherapeutic conventional surgeryLumpectomy or mastectomy will be performed follwoing day 29 of study therapy

Timeline

Start date
2010-10-01
Primary completion
2017-05-01
Completion
2017-05-01
First posted
2010-11-04
Last updated
2022-05-03
Results posted
2022-05-03

Locations

1 site across 1 country: United States

Source: ClinicalTrials.gov record NCT01234532. Inclusion in this directory is not an endorsement.