Reversing Therapy Resistance With Epigenetic-Immune Modification

Breast Neoplasms Clinical Trial

Official title: Reversing Therapy Resistance With Epigenetic-immune Modification: Phase II Trial of Vorinostat, Tamoxifen and Pembrolizumab in Hormone Receptor Expressing Advanced Breast Cancer

Status Terminated

Clinical Trial Summary

The investigators propose a randomized two arm trial, using Simon's 2-stage design, in ER+ patients with therapy resistant breast cancer to test the optimal sequence and dosing of epigenetic immune priming in hormone therapy resistance breast cancer. A third arm (Arm C) will include ER-negative patients who will follow the concurrent priming, but exclude tamoxifen. The two arms all include vorinostat, tamoxifen, and pembrolizumab to evaluate

• Sequential priming - begin pembrolizumab in Cycle 1 (Arm B and Arm C) and,

• Concurrent priming with maximal dosing of both epigenetic and immune modulators- begin pembrolizumab on day 1 in Cycle 2 (Arm A)

Clinical Trial Description

Unique aspects of this study:

This is the first study to look at the response of hormone therapy resistance breast cancer to epigenetic immune priming. It is also the first study to look at the combination of an Histone deacetylase (HDAC) inhibitor (vorinostat), an anti-estrogen (tamoxifen) and a PD-1 inhibitor, pembrolizumab in pre or postmenopausal patients with ER+ advanced breast cancer with progression on multiple prior therapies.

Recent preclinical studies have further suggested that epigenetic priming may be even more effective in ER-negative tumors that do not respond to immune check point inhibitors or have low PD-1/PD-L1 expression. The goal of this study is to demonstrate that Vorinostat can increase PD-1 and PD-L1 expression.

In a third arm the study will evaluate the role of epigenetic priming in tumors that are ER-negative. ;

Related Conditions & MeSH terms

• Breast Neoplasms

• NCT number: NCT02395627
• Study type: Interventional
• Source: University of California, San Francisco
• Status: Terminated
• Phase: Phase 2
• Start date: May 4, 2015
• Completion date: June 8, 2019