NCT07276880 · UNC Lineberger Comprehensive Cancer Center
Preoperative Chemotherapy, Pembrolizumab and Low or High Dose RADiation in an Expansion Cohort of Node(+), Triple Negative Breast Cancer
(P-RAD(+)TN-DCT)
What this study is about
This is a forward-looking radiation dose-finding, phase 2 expansion study of the Triple Negative (TN) group of participants of the conducted at multiple hospitals randomly assigned study P-RAD (A randomly assigned 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 the usual treatment neoadjuvant chemo-immunotherapy (NAC) based on the KEYNOTE-522 clinical trial. Thirty-two (n=32) patients will be randomly assigned 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 the usual treatment surgical resection of the breast and axillary lymph nodes, at the discretion of their surgical oncology provider. In the Adjuvant Phase, participants will receive the usual treatment adjuvant systemic therapy and the usual treatment 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.
View original scientific description
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.
Interventions
DRUG
Neoadjuvant Pembrolizumab
200 milligrams per square meter Neoadjuvant Pembrolizumab will be administered intravenously.
RADIATION
low dose neoadjuvant boost
An external beam radiotherapy boost of 9Gy total will be administered over 3 fractions.
RADIATION
High dose neoadjuvant boost
An external beam radiotherapy boost of 24Gy total will be administered over 3 fractions.
Primary outcome measures
Nodal Pathologic Complete Response rate(pCR)
Time frame: Time of surgery (24 week)
Nodal pCR is defined in a patient with no residual cancer cells in all sampled regional lymph nodes following completion of neoadjuvant systemic therapy as assessed by the study pathologist at the time of definitive surgery. Nodal pCR rates will be calculated and analyzed separately for patients receiving low versus high dose RT. A pooled analysis, incorporating the corresponding (3Gyx3 or 8Gyx3) patient cohort from the P-RAD trial, will be performed.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- In order to participate in this study, a subject must meet all of the eligibility criteria outlined below.
- 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
Where
- Chapel Hill, North Carolina
Collaborators
National Cancer Institute (NCI), Merck Sharp & Dohme LLC
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Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Apr 27, 2026 · Source of record for eligibility and locations