Pembrolizumab with and without Intra-operative Radiation Therapy in Treating Patients with Triple Negative Breast Cancer

Active:	Yes
Cancer Type:	Breast Cancer	NCT ID:	NCT02977468
Trial Phases:	Phase I	Protocol IDs:	AAAQ7863 (primary) NCI-2017-01380
Eligibility:	21 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
NCI Full Details:	http://clinicaltrials.gov/show/NCT02977468

Summary

This phase I trial studies how well pembrolizumab works in treating patients with triple negative breast cancer with and without intra-operative radiation therapy. 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. Intra-operative radiation therapy involves radiation treatment aimed directly at a tumor during surgery. Giving pembrolizumab with intra-operative radiation therapy may work better in treating patients with triple negative breast cancer.

Objectives

PRIMARY OBJECTIVE:
I. Assess for change in tumor-infiltrating lymphocytes (TILS) both stromal (sTILS) and intraepithelial (iTILS) in newly diagnosed early stage triple negative breast cancer (TNBC) patients treated with pembrolizumab (MK-3475) prior to lumpectomy.

SECONDARY OBJECTIVES:
I. Measure patient response with histopathologic features of the tumor microenvironment as assessed by PD-1, PD-L1, and PD-L2 expression, quantification of infiltrating CD8+ T cells at the invasive margin and within the center of the tumor, and assessment of CD2 expression.
II. Measure patient response using genomic features of the tumor microenvironment as assessed by NanoString with measurement of immune related genes (53 gene panel).
III. Evaluate the total phosphoproteome profile by liquid chromatography (LC)-mass spectrometry (MS/MS) analysis of adjacent “normal” breast tissue compared to immune markers/gene expression above.
IV. Determine if significant alteration in immune pathways occur following single fraction intra-operative radiation therapy (IORT) in breast microenvironment.

EXPLORATORY OBJECTIVES:
I. Compare protein profile from tissue specimens to serum exosomes isolated from serial blood specimens collected from the same patient.
II. Determine if serum exosome profile can be used to monitor drug efficacy as well as potential toxicity by comparing IORT with and without PD1 antibody (Ab).
III. Utilize matrix-assisted laser desorption/ionization (MALDI)-mass spectrometric imaging (MSI) imaging for localization of targeted proteins.
IV. Explore effects on circulating lymphocytes of preoperative exposure to MK-3475.

OUTLINE:
Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Beginning 8-18 days later, patients undergo lumpectomy and intra-operative radiation therapy.

After completion of study treatment, patients are followed up 10-30 days after surgery.

Treatment Sites in Georgia

Winship Cancer Institute of Emory University
1365 Clifton Road NE
Building C
Atlanta, GA 30322
404-778-5180
winshipcancer.emory.edu

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.