NCT04443348

Pre-op Pembro + Radiation Therapy in Breast Cancer (P-RAD)

P-RAD: A Randomized Study of Preoperative Chemotherapy, Pembrolizumab and No, Low or High Dose RADiation in Node-Positive, HER2-Negative Breast Cancer

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sponsor: Laura M. Spring, MD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This research trial is studying a combination of neoadjuvant radiotherapy (RT), immunotherapy (pembrolizumab) and chemotherapy for lymph node-positive, triple negative (TN) or hormone receptor positive/HER2-negative breast cancer. The names of the study interventions involved in this study are: * Radiation Therapy (RT) * Immunotherapy: Pembrolizumab (MK-3475) * Chemotherapies: * Paclitaxel * Doxorubicin (also called Adriamycin) * Cyclophosphamide * Carboplatin (optional, and in TN only) * Capecitabine (optional, and in TN only)

Detailed description

The main purpose of this study is to find out what is the best dose of preoperative RT when combined with pembrolizumab and chemotherapy. The study will assess if combining the RT with the immunotherapy agent, pembrolizumab, will increase the ability of the immune system to destroy cancer cells. The research study procedures include: screening for eligibility and study treatment, including evaluations and follow-up visits. The study aims to assess the effectiveness of pembrolizumab (study drug) with or without RT directed to the breast tumor. Participants will then undergo neoadjuvant chemotherapy with pembrolizumab, followed by treatment that can consist of one or more of the following: * Pembrolizumab (optional, per MD discretion) * Standard of Care Treatment * Breast surgery (lumpectomy or mastectomy) and axillary surgery * Adjuvant radiation to the entire breast or chest wall, plus or minus the lymph nodes after surgery * Adjuvant chemotherapy (optional Capecitabine for TNBC patients) * Hormone therapy Participants will be randomized to 1 of 3 groups. Neither the participant not the research doctor will choose the group that the participant is assigned to. However, the participant will be notified of the group prior to the start of study treatment. Participants will receive study treatment for up to 13 months. Participants will be followed for 2 years after the end of the study treatment. It is expected that a total of 120 people will be participating in total. This research study is a randomized, phase II study. The U.S. Food and Drug Administration (FDA) has not approved pembrolizumab for your specific disease, but it has been approved for other uses. The U.S. Food and Drug Administration (FDA) has approved the chemotherapies being used in this study (Paclitaxel, Doxorubicin, Cyclophosphamide, Carboplatin, Capecitabine).

Conditions

• Triple Negative Breast Cancer
• Hormone Receptor Positive (HR+), HER2-negative Breast Cancer
• Biopsy-proven, Positive Lymph Node(s)

Interventions

Type	Name	Description
RADIATION	Radiation Therapy Boost	Participants randomized to the low-dose or high-dose RT boost group will be receiving treatment on Day 1-3 of Cycle 1 of pembrolizumab. Proton therapy may be used in the high dose RT group.
DRUG	Pembrolizumab	Neoadjuvant Phase: Day 1 (once every 6 weeks) of Cycles 1-4 (by intravenous infusion) over about 30 minutes. Adjuvant Phase: Pembrolizumab may be given post-surgery for up to 4 cycles (once every 6 weeks) by intravenous infusion over about 30 minutes. Pembrolizumab after surgery is optional and should be discussed with the study doctor.
DRUG	Paclitaxel	Starting Week 3 and administered once per week for 12 weeks (up to 12 doses) by intravenous infusion over about 30 minutes.
DRUG	Carboplatin	Carboplatin is optional for TNBC patients and should be discussed with the study doctor. Starting Week 3 and administered once per week for 12 weeks (up to 12 doses) by intravenous infusion over about 30 minutes.
DRUG	Cyclophosphamide	Starting Week 15 and administered every 2 weeks for 4 cycles (up to 4 doses) into your vein (by intravenous infusion).
DRUG	Doxorubicin	Starting Week 15 and administered every 2 weeks for 4 cycles (up to 4 doses) into your vein (by intravenous infusion). Doxorubicin will be administered after pembrolizumab.
DRUG	Capecitabine	Capecitabine after surgery is optional for TNBC patients and should be discussed with the study doctor. Starting 3-6 weeks after surgery, administered orally twice daily for 6 courses, each 3 weeks long (for a total of 18 weeks).

Timeline

• Start date: 2020-12-16
• Primary completion: 2025-08-08
• Completion: 2027-08-01
• First posted: 2020-06-23
• Last updated: 2025-10-14

Locations

10 sites across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study