Preoperative Chemotherapy, Pembrolizumab and Low or High Dose RADiation in an Expansion Cohort of Node(+), Triple Negative Breast Cancer

NCT ID: NCT07276880

Last Updated: 2026-01-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-31

Study Completion Date

2032-01-31

Brief Summary

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This is a prospective radiation dose-finding, phase 2 expansion study of the Triple Negative (TN) cohort of the multicenter randomized study P-RAD (A Randomized Study of Preoperative Chemotherapy, Pembrolizumab and No, Low or High Dose RADiation in Node-Positive, HER2-Negative Breast Cancer; NCT04443348) that seeks to establish the optimal dose of radiation therapy (RT) to elicit an immune response when combined with immune checkpoint inhibitor (ICI) in breast cancer patients. Eligible subjects include women or men with operable, lymph node-positive, triple negative (TN) breast cancer who are candidates for standard of care neoadjuvant chemo-immunotherapy (NAC) based on the KEYNOTE-522 clinical trial. Thirty-two (n=32) patients will be randomized 1:1 to receive either low RT boost (9Gy total) or high RT boost (24Gy total). All RT will be delivered to the intact breast tumor in 3 daily fractions over 3 days.

In the Neoadjuvant Phase, the first cycle (C1) of pembrolizumab (200 mg i.v.) will be administered within 0-2 days of initiating RT. Participation in this study requires availability of residual diagnostic tissue biopsies of the primary tumor and metastatic lymph node for research use. If this tissue is not available, baseline research biopsies will be performed. Additionally, a research biopsy of the breast tumor and lymph node is required on Day 10-14 of C1 of pembrolizumab. After completion of the research biopsy in Week 2, the participants can commence standard-of-care neoadjuvant chemotherapy and pembrolizumab at the discretion of their medical oncology provider. After completing NAC, participants will undergo standard of care surgical resection of the breast and axillary lymph nodes, at the discretion of their surgical oncology provider. In the Adjuvant Phase, participants will receive standard of care adjuvant systemic therapy and standard of care adjuvant radiotherapy (if indicated), although recognizing that the breast tumor boost portion of this treatment has already been administered preoperatively. Except for late radiation adverse reactions of special interest, which will be followed yearly for up to 5 years, follow-up will occur every 6 months for 3 years.

Detailed Description

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Conditions

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Breast Cancer Triple Negative Breast Cancer (TNBC) HER2-Negative Breast Carcinoma Node-positive Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

hybrid decentralized
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ARM 1

Participants will receive a low dose radiation therapy boost in 3 fractions (3Gy x 3 fraction = 9Gy total).

Group Type EXPERIMENTAL

Neoadjuvant Pembrolizumab

Intervention Type DRUG

200 milligrams per square meter Neoadjuvant Pembrolizumab will be administered intravenously.

low dose neoadjuvant boost

Intervention Type RADIATION

An external beam radiotherapy boost of 9Gy total will be administered over 3 fractions.

ARM 2

Participants will receive a high dose radiation therapy boost in 3 fractions (8Gy x 3 fraction = 24Gy total).

Group Type EXPERIMENTAL

Neoadjuvant Pembrolizumab

Intervention Type DRUG

200 milligrams per square meter Neoadjuvant Pembrolizumab will be administered intravenously.

High dose neoadjuvant boost

Intervention Type RADIATION

An external beam radiotherapy boost of 24Gy total will be administered over 3 fractions.

Interventions

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Neoadjuvant Pembrolizumab

200 milligrams per square meter Neoadjuvant Pembrolizumab will be administered intravenously.

Intervention Type DRUG

low dose neoadjuvant boost

An external beam radiotherapy boost of 9Gy total will be administered over 3 fractions.

Intervention Type RADIATION

High dose neoadjuvant boost

An external beam radiotherapy boost of 24Gy total will be administered over 3 fractions.

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

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* Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information. Subjects are willing and able
* to comply with study procedures based on the judgment of the investigator.
* Age ≥ 18 years at the time of consent.
* ECOG or Karnofsky Performance Status of 0 or 1

Exclusion Criteria

* Active infection requiring systemic therapy.
* Pregnant or breastfeeding.
* Prior ipsilateral invasive breast, chest wall or thoracic radiotherapy
* Prior ipsilateral invasive breast cancer, contralateral breast cancer or a known
* additional, invasive malignancy that is progressing or required active treatment in
* the last 5 years
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dana Casey, MD

Role: PRINCIPAL_INVESTIGATOR

UNC Lineberger Comprehensive Cancer Center

Locations

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University of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Countries

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United States

Central Contacts

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Taylor Pierce

Role: CONTACT

919-984-0000

Emily L Schworer

Role: CONTACT

919-984-0000

Related Links

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http://unclineberger.org/patientcare/clinical-trials/clinical-trials

University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

Other Identifiers

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R01CA274254

Identifier Type: NIH

Identifier Source: secondary_id

View Link

LCCC2426-DCT

Identifier Type: -

Identifier Source: org_study_id

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