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

Running, not enrolling · Phase 2

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

In brief

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)

Key facts

Study ID

NCT04443348

Run by

Laura M. Spring, MD

People needed

120

Starts

2020-12-16

Expected to finish

2026-12-31

Last updated by the study team

2026-07-13

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age ≥18 years old
• Participant has non-metastatic, T1*-T2 and N1-3 and one of the following histologically confirmed disease subtypes:
• - Triple negative breast cancer is defined as ER-negative (<1% cells), PR-negative (<1% cells) and HER2-negative (<2+ HER2 IHC or <2.2 HER2/CEP17 ratio by FISH), as per testing at local institution
• High-risk HR+/HER2-negative breast cancer is defined as ER≥1%, HER2-negative (<2+ Her2 IHC or <2.2 HER2/CEP17 ratio by FISH) and either histologic grade II-III or a high-risk genomic assay score (Oncotype RS>25, high risk Mammaprint, PAM-50, EndoPredict or ProSigna score).
• Note: Eligibility requires primary tumor size ≥1.0 cm in maximum diameter and axillary node-positive breast cancer
• Primary breast tumor measuring ≥1.5 cm in maximal diameter as measured by any available standard of care imaging (mammogram, breast ultrasound, breast MRI).
• Biopsy-proven, axillary lymph node-positive breast cancer at diagnosis. Note: Clinically node-positive disease is classified as cN1-3. cN1: without matted nodes, even if several/multiple appear matted on ultrasound or MRI; cN2: clinically fixed or matted nodes on examination or clinically or imaging-detected internal mammary node involvement.
• Clips or fiducial placement within the biopsy-proven axillary lymph node and breast primary tumor are required.
• Multifocal and multicentric disease is permitted; however only one breast tumor may be preoperatively boosted.
• -Note: For patients with multifocal disease and are randomized to receive a preoperative RT boost, all sites of multifocal disease should be contained within the pre-operative boost volume. Subsequently, these patients will not need a post-op boost.
• Synchronous bilateral invasive breast cancer is permitted; however only one breast tumor may be preoperatively boosted.
• No indication of distant metastases. Staging scans are not required and are per the discretion of the treating physician.
• Neoadjuvant chemotherapy (NAC) with paclitaxel, dose-dense doxorubicin and cyclophosphamide (dd AC) is planned. Note: For TNBC patients, administration of carboplatin is optional, as per MD choice. For HR+ patients, carboplatin will not be administered.
• The boost volume is determined to be able to meet study dose constraints by the treating radiation oncologist.
• Breast-conserving surgery or mastectomy +/- reconstruction is planned following NAC.
• ECOG performance status score of 0 or 1.
• Have adequate organ function as defined in the following table. Bloodwork must be collected within 10 days prior to the start of study treatment.
• Hematological --- Absolute neutrophil count (ANC) ≥1500/µL
• Platelets ≥100 000/µL
• Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La
• Renal
• -- Creatinine ≤1.5 × ULN OR Measured or calculated b creatinine clearance (GFR can also be used in place of creatinine or CrCl) OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN
• Hepatic
• Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
• AST (SGOT) and ALT (SGPT) ≤2.5 × ULN

You may not qualify if…

• HER2-positive breast cancer by ASCO/CAP guidelines (HER2 IHC 3+ or ≥ 2.2 HER2/CEP17 ratio by FISH)
• Inflammatory (cT4d) breast cancer
• Metastatic breast cancer (M1)
• Contraindication(s) to breast-conserving therapy or mastectomy
• Contraindication to radiation therapy including: prior ipsilateral breast or mantle RT, active scleroderma, systemic lupus erythematosis and pregnancy.
• -Note: All cardiac implantable electronic devices are permitted, provided that methods to assess radiation doses and minimize damage to the devices during RT is planned, per institutional guidelines.
• Prior ipsilateral 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.
• -Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or cervical carcinoma in situ that has undergone potentially curative therapy and a previous diagnosis of ductal carcinoma in situ are not excluded.
• Has a known history of active tuberculosis (Bacillus tuberculosis
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to randomization.
• -Note: Participants must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy may be eligible. If participant received major surgery, she/he must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has known severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Participants with active, known or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authorities.
• Known active Hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected). Note: Testing for hepatitis B or hepatitis C is not required, unless mandated by local health authorities or institutional guidelines.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist®) are live attenuated vaccines and are not allowed.
• Has had an allogenic tissue/solid organ transplant
• A WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of study treatment (see Appendix A). If the urine test cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
• Prohibited Treatments and/or Therapies:Use of immunosuppressants and/or systemic corticosteroids is exclusionary, except the following in the absence of active autoimmune disease:
• As premedication for chemotherapy
• For the prevention of nausea in the three days following chemotherapy

Where it is running

• Sibley Memorial Hospital — Washington D.C., District of Columbia, United States
• Johns Hopkins — Baltimore, Maryland, United States
• Massachusetts General Hospital — Boston, Massachusetts, United States
• Dana Farber Cancer Institute — Boston, Massachusetts, United States
• Mayo Clinic - Rochester — Rochester, Minnesota, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• Montefiore Medical Center — The Bronx, New York, United States
• University of North Carolina Medical Center — Chapel Hill, North Carolina, United States
• Duke University Medical Center — Durham, North Carolina, United States
• MD Anderson Cancer Center — Houston, Texas, United States

Full record on ClinicalTrials.gov

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