Effects of MK-3475 (Pembrolizumab) on the Breast Tumor Microenvironment in Triple Negative Breast Cancer (Pembro/IORT)
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|ClinicalTrials.gov Identifier: NCT02977468|
Recruitment Status : Recruiting
First Posted : November 30, 2016
Last Update Posted : September 24, 2019
Assess response to pembrolizumab in both primary tumor, normal breast stroma, circulating lymphocytes and serum exosomes in treatment naive triple negative breast cancer (TNBC) patients.
Assess for change in tumor-infiltrating lymphocytes (TILS) both stromal (sTILS) and intraepithelial (iTILS) in newly diagnosed early stage TNBC patients treated with two doses of MK-3475 prior to lumpectomy.
|Condition or disease||Intervention/treatment||Phase|
|Triple Negative Breast Cancer||Drug: Merck 3475 Pembrolizumab Radiation: Intraoperative radiation therapy (IORT)||Phase 1|
This is an open-label, single-arm, single institution pre-operative "window of opportunity study" of pembrolizumab in subjects with newly diagnosed triple-negative, < 3 cm, node negative breast cancer. Subjects may not have received any prior neo/adjuvant chemotherapy, definitive surgery or radiation treatment prior to enrollment.
The goal of this project is to determine if immune modulation through treatment with MK-3475 (Pembrolizumab) in triple negative breast cancer (TNBC) patients will alter expression of immune tolerant markers [including PD-L1], within the primary tumor. Investigators hope to determine if MK-3475 exposure will change the molecular signature of breast stroma from "normal" adjacent breast tissue (non-tumor tissue) obtained prospectively at the time of breast conserving surgery (BCS) in TNBC patients. Finally, investigators will investigate how pembrolizumab alters breast stromal response to high dose radiation delivered by intraoperative radiation therapy (IORT).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Effects of MK-3475 (Pembrolizumab) on the Breast Tumor Microenvironment in Triple Negative Breast Cancer With and Without Intra-operative RT: a Window of Opportunity Study|
|Actual Study Start Date :||October 25, 2017|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||December 2021|
Experimental: Single Arm open label
Participants receive 'Merck 3475 Pembrolizumab' by vein one to two times before Intraoperative radiation therapy (IORT).
The Intrabeam® Photon Radiosurgery System is a miniature electron beam-driven X-ray source which provides a point source of low energy X-rays (50 kV maximum) at the tip of a 3.2 mm diameter tube. The radiation source can be inserted into the area of interest immediately after excision of the tumor and switched on for 20-35 minutes to provide intraoperative radiotherapy accurately targeted to the tissues that are at the highest risk of local recurrence. The dosimetric characteristics and early clinical applications of this device have been well studied and this is the device which was utilized in the international TARGIT trial.
Drug: Merck 3475 Pembrolizumab
Participants receive Pembrolizumab by vein over about 30 minutes on Day 1 of one to two cycles.
Radiation: Intraoperative radiation therapy (IORT)
Participants will receive Intraoperative radiation therapy (IORT) on the day of surgery.
- Number of subjects with significant mean percent change in TILs [ Time Frame: 3 months ]This outcome measure is designed to determine if immune modulation therapy with MK-3475 will increase TILs in newly diagnosed TNBC tumors. The mean percent change in TILS in tumor tissue from initial core biopsy samples will be compared with pathology samples from definitive surgery after two cycles of MK-3475.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02977468
|Contact: Eileen Connolly, MDemail@example.com|
|Contact: Radiation Oncology Research Department||212-305-5050|
|United States, New York|
|Columbia University Medical Center||Recruiting|
|New York, New York, United States, 10032|
|Contact: Eileen Connolly, MD 212-305-5050 firstname.lastname@example.org|
|Contact: Mariamne Reyna 646-317-4244 email@example.com|
|Principal Investigator: Eileen Connolly, MD, PhD|
|Principal Investigator:||Eileen Connolly, MD||Assistant Professor Of Radiation Oncology|