Preoperative Chemotherapy, Pembrolizumab and Low or High Dose RADiation in an Expansion Cohort of Node(+), Triple Negative Breast Cancer
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Neoadjuvant Pembrolizumab, low dose neoadjuvant boost, High dose neoadjuvant boost.
- Who it may be relevant to
- Registry conditions: Breast Cancer, Triple Negative Breast Cancer (TNBC), HER2-Negative Breast Carcinoma, Node-positive Breast Cancer. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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)]
Secondary outcome measures (12)
- The CD3+/CD8+ T cell Breast post-treatment biopsy [Time frame: Time of surgery (24 week)]
- Composite pathologic complete response (pCR) (ypT0/Tis ypN0) [Time frame: Time of surgery (24 week)]
- Total residual cancer burden (RCB) [Time frame: Time of surgery (24 week)]
- Nodal pathologic complete response (pCR) [Time frame: Time of surgery (24 week)]
- Composite pathologic complete response (pCR) [Time frame: Time of surgery (24 week)]
- Changes in pre- versus post-treatment intra-tumoral, peri-tumoral, and stromal CD3+ or CD8+ T cell percentages [Time frame: Time of surgery (24 week)]
- Change in tumor-infiltrating lymphocyte (TIL) [Time frame: Time of surgery (24 week)]
- Change in Programmed cell death 1 ligand 1(PD-L1) [Time frame: Time of surgery (24 week)]
- Changes in intratumoral, peri-tumoral, and stromal CD4+Foxp3+ T regulatory cell densities [Time frame: Time of surgery (24 week)]
- Adverse Events [Time frame: Up to 60 weeks]
- Invasive disease-free survival (iDFS) [Time frame: Up to 5 years]
- Event-free survival (EFS) [Time frame: Up to 5 years]
Eligibility criteria
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 1 center
- University of North Carolina — Chapel Hill
Identifiers
NCT: NCT07276880 · LCCC2426-DCT · R01CA274254