Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-24 @ 11:28 PM
Ignite Modification Date:
2025-12-24 @ 11:28 PM
NCT ID:
NCT04190056
Brief Summary:
This phase II trial studies how well pembrolizumab and tamoxifen with or without vorinostat work for the treatment of estrogen receptor positive breast cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Estrogen can cause the growth of breast cancer cells. Hormone therapy with tamoxifen may may fight breast cancer by blocking the use of estrogen by the tumor cells. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This trial is being done to find a drug combination to better control estrogen receptor positive breast cancer and reduce the number of pills taken.
Detailed Description:
PRIMARY OBJECTIVE:
I. To define the role of epigenetic immune priming in a biomarker enriched estrogen receptor (ER)+ breast cancer population on the basis of overall response rate.
SECONDARY OBJECTIVES:
I. To assess duration of response (DOR) 24-week landmark progression-free survival (PFS:24).
II. Median PFS and overall survival (OS). III. Tumor responses will also be calculated by Immune Related Response-Criteria (irRC).
EXPLORATORY OBJECTIVES:
I. Evaluation of biomarker target threshold on response rate (retrospective cut off of 20% versus \[vs\] 10%).
II. To assess the ratio of effector T cells: regulatory T cells in blood and tumor biopsies pre- and post-therapy.
III. To evaluate inflammatory T cell signature changes in blood and tumor biopsies pre- and post-therapy.
IV. To evaluate changes in number of myeloid-derived suppressor cells (MDSCs) in peripheral blood and tumor biopsies pre- and posttherapy.
V. To evaluate changes in histone acetylation in peripheral blood cells and tumor biopsies pre- and post-therapy.
VI. Initial comparison to vorinostat-induced PD-1 in lymphocytes, PD-L1 modulation.
VII. Nanostring and 10 x sequencing and single cell immune phenotyping (on stored tissue for successful arms only).
VIII. Impact of histone deacetylase (HDAC) inhibition of response to pembrolizumab vs. pembrolizumab in biomarker enriched population.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1, vorinostat orally (PO) once daily (QD) for 4 days weekly, and tamoxifen PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression of unacceptable toxicity.
ARM B: Patients receive pembrolizumab IV over 30 minutes on day 1 and tamoxifen PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression of unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days and then every 12 weeks thereafter.
Study:
NCT04190056
Study Brief:
Protocol Section:
NCT04190056