Pembrolizumab with and without Intra-operative Radiation Therapy in Treating Patients with Triple Negative Breast Cancer
21 Years and older, Male and Female
AAAQ7863 (primary)
NCI-2017-01380
Summary
This phase I trial studies how well pembrolizumab works in treating patients with triple negative breast cancer with and without intra-operative radiation therapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Intra-operative radiation therapy involves radiation treatment aimed directly at a tumor during surgery. Giving pembrolizumab with intra-operative radiation therapy may work better in treating patients with triple negative breast cancer.
Objectives
PRIMARY OBJECTIVE:
I. Assess for change in tumor-infiltrating lymphocytes (TILS) both stromal (sTILS) and intraepithelial (iTILS) in newly diagnosed early stage triple negative breast cancer (TNBC) patients treated with pembrolizumab (MK-3475) prior to lumpectomy.
SECONDARY OBJECTIVES:
I. Measure patient response with histopathologic features of the tumor microenvironment as assessed by PD-1, PD-L1, and PD-L2 expression, quantification of infiltrating CD8+ T cells at the invasive margin and within the center of the tumor, and assessment of CD2 expression.
II. Measure patient response using genomic features of the tumor microenvironment as assessed by NanoString with measurement of immune related genes (53 gene panel).
III. Evaluate the total phosphoproteome profile by liquid chromatography (LC)-mass spectrometry (MS/MS) analysis of adjacent “normal” breast tissue compared to immune markers/gene expression above.
IV. Determine if significant alteration in immune pathways occur following single fraction intra-operative radiation therapy (IORT) in breast microenvironment.
EXPLORATORY OBJECTIVES:
I. Compare protein profile from tissue specimens to serum exosomes isolated from serial blood specimens collected from the same patient.
II. Determine if serum exosome profile can be used to monitor drug efficacy as well as potential toxicity by comparing IORT with and without PD1 antibody (Ab).
III. Utilize matrix-assisted laser desorption/ionization (MALDI)-mass spectrometric imaging (MSI) imaging for localization of targeted proteins.
IV. Explore effects on circulating lymphocytes of preoperative exposure to MK-3475.
OUTLINE:
Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Beginning 8-18 days later, patients undergo lumpectomy and intra-operative radiation therapy.
After completion of study treatment, patients are followed up 10-30 days after surgery.
Eligibility
- Ability to understand and the willingness to sign a written informed consent document.
- Be >= 21 years of age on day of signing informed consent
- Histologically proven invasive breast carcinoma with triple negative receptor status (estrogen receptor, progesterone receptor and HER2 negative by immunohistochemistry [IHC] and/or fluorescence in situ hybridization [FISH]); patients who are weekly positive for the estrogen or progesterone receptor (i.e. =< 10%) are eligible
- Clinically =< 3 cm unifocal lesion by imaging or physical examination
- Clinically node negative, no evidence of metastatic disease
- No prior systemic anti-cancer therapy including investigational agents, radiation therapy, or breast resection within 6 months of study entry
- Breast size B cup or larger, to allow for IORT procedure
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
- Absolute neutrophil count (ANC) >= 1,500 /uL
- Platelets >= 100,000 /uL
- Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L; criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
- Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 30 mL/min for participant with creatinine levels > 1.5 x institutional ULN.
- Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 x ULN.
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN.
- International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants.
- Activated partial thromboplastin Time (aPTT) =< 1.5 X ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Note: In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication
- Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication
* Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
Treatment Sites in Georgia
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