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

Обзор

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.

Вмешательства

• Препарат Neoadjuvant Pembrolizumab
  200 milligrams per square meter Neoadjuvant Pembrolizumab will be administered intravenously.
• Лучевая терапия low dose neoadjuvant boost
  An external beam radiotherapy boost of 9Gy total will be administered over 3 fractions.
• Лучевая терапия High dose neoadjuvant boost
  An external beam radiotherapy boost of 24Gy total will be administered over 3 fractions.

Первичные конечные точки

• Nodal Pathologic Complete Response rate(pCR) [Срок оценки: Time of surgery (24 week)]

Вторичные конечные точки (12)

• The CD3+/CD8+ T cell Breast post-treatment biopsy [Срок оценки: Time of surgery (24 week)]
• Composite pathologic complete response (pCR) (ypT0/Tis ypN0) [Срок оценки: Time of surgery (24 week)]
• Total residual cancer burden (RCB) [Срок оценки: Time of surgery (24 week)]
• Nodal pathologic complete response (pCR) [Срок оценки: Time of surgery (24 week)]
• Composite pathologic complete response (pCR) [Срок оценки: Time of surgery (24 week)]
• Changes in pre- versus post-treatment intra-tumoral, peri-tumoral, and stromal CD3+ or CD8+ T cell percentages [Срок оценки: Time of surgery (24 week)]
• Change in tumor-infiltrating lymphocyte (TIL) [Срок оценки: Time of surgery (24 week)]
• Change in Programmed cell death 1 ligand 1(PD-L1) [Срок оценки: Time of surgery (24 week)]
• Changes in intratumoral, peri-tumoral, and stromal CD4+Foxp3+ T regulatory cell densities [Срок оценки: Time of surgery (24 week)]
• Adverse Events [Срок оценки: Up to 60 weeks]
• Invasive disease-free survival (iDFS) [Срок оценки: Up to 5 years]
• Event-free survival (EFS) [Срок оценки: Up to 5 years]

Критерии участия

Критерии включения

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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of North Carolina — Chapel Hill

Идентификаторы

NCT: NCT07276880 · LCCC2426-DCT · R01CA274254

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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