Preoperative Chemotherapy, Pembrolizumab and Low or High Dose RADiation in an Expansion Cohort of Node(+), Triple Negative Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Nodal Pathologic Complete Response rate(pCR)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
ARM 1
Participants will receive a low dose radiation therapy boost in 3 fractions (3Gy x 3 fraction = 9Gy total).
干预措施: Neoadjuvant Pembrolizumab (Drug)
ARM 1
Participants will receive a low dose radiation therapy boost in 3 fractions (3Gy x 3 fraction = 9Gy total).
干预措施: low dose neoadjuvant boost (Radiation)
ARM 2
Participants will receive a high dose radiation therapy boost in 3 fractions (8Gy x 3 fraction = 24Gy total).
干预措施: Neoadjuvant Pembrolizumab (Drug)
ARM 2
Participants will receive a high dose radiation therapy boost in 3 fractions (8Gy x 3 fraction = 24Gy total).
干预措施: High dose neoadjuvant boost (Radiation)
结局指标
主要结局
Nodal Pathologic Complete Response rate(pCR)
时间窗: 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.
次要结局
- Composite pathologic complete response (pCR) (ypT0/Tis ypN0)(Time of surgery (24 week))
- Total residual cancer burden (RCB)(Time of surgery (24 week))
- Nodal pathologic complete response (pCR)(Time of surgery (24 week))
- Composite pathologic complete response (pCR)(Time of surgery (24 week))
- Changes in pre- versus post-treatment intra-tumoral, peri-tumoral, and stromal CD3+ or CD8+ T cell percentages(Time of surgery (24 week))
- Change in tumor-infiltrating lymphocyte (TIL)(Time of surgery (24 week))
- Event-free survival (EFS)(Up to 5 years)
- Quality of life Global Health PROMIS in Low Dose Radiotherapy Boost Group(Baseline, Week 2, Week 8, Week 14, and Week 20, 6 months post-surgery, and monthly for up to 3 years)
- Quality of life BREAST-Q in Low Dose Radiotherapy Boost Group(Baseline, Week 2, Week 8, Week 14, and Week 20, 6 months post-surgery, and monthly for up to 3 years)
- The Was It Worth It (WIWI) in Low Dose Radiotherapy Boost Group(Baseline, Week 2, Week 8, Week 14, and Week 20, 6 months post-surgery, and monthly for up to 3 years)
- Quality of life Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in Low Dose Radiotherapy Boost Group(Baseline, Week 2, Week 8, Week 14, and Week 20, 6 months post-surgery, and monthly for up to 3 years)
- Comparison tumor-infiltrating lymphocyte (TIL)(Time of surgery (24 week))
- The CD3+/CD8+ T cell Breast post-treatment biopsy(Time of surgery (24 week))
- Composite pathologic complete response (pCR) (ypT0/Tis ypN0)(Time of surgery (24 week))
- Total residual cancer burden (RCB)(Time of surgery (24 week))
- Nodal pathologic complete response (pCR)(Time of surgery (24 week))
- Composite pathologic complete response (pCR)(Time of surgery (24 week))
- Changes in pre- versus post-treatment intra-tumoral, peri-tumoral, and stromal CD3+ or CD8+ T cell percentages(Time of surgery (24 week))
- Change in tumor-infiltrating lymphocyte (TIL)(Time of surgery (24 week))
- Change in Programmed cell death 1 ligand 1(PD-L1)(Time of surgery (24 week))
- Changes in intratumoral, peri-tumoral, and stromal CD4+Foxp3+ T regulatory cell densities(Time of surgery (24 week))
- Adverse Events(Up to 60 weeks)
- Invasive disease-free survival (iDFS)(Up to 5 years)
- Event-free survival (EFS)(Up to 5 years)
- Quality of life Global Health PROMIS in Low Dose Radiotherapy Boost Group(Baseline, Week 2, Week 8, Week 14, and Week 20, 6 months post-surgery, and monthly for up to 3 years)
- Quality of life BREAST-Q in Low Dose Radiotherapy Boost Group(Baseline, Week 2, Week 8, Week 14, and Week 20, 6 months post-surgery, and monthly for up to 3 years)
- The Was It Worth It (WIWI) in Low Dose Radiotherapy Boost Group(Baseline, Week 2, Week 8, Week 14, and Week 20, 6 months post-surgery, and monthly for up to 3 years)
- Quality of life Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in Low Dose Radiotherapy Boost Group(Baseline, Week 2, Week 8, Week 14, and Week 20, 6 months post-surgery, and monthly for up to 3 years)
- Comparison tumor-infiltrating lymphocyte (TIL)(Time of surgery (24 week))