Clinical Trials /

Effects of MK-3475 (Pembrolizumab) on the Breast Tumor Microenvironment in Triple Negative Breast Cancer

NCT02977468

Description:

Assess response to pembrolizumab in both primary tumor, normal breast stroma, circulating lymphocytes and serum exosomes in treatment naive triple negative breast cancer (TNBC) patients. Assess for change in tumor-infiltrating lymphocytes (TILS) both stromal (sTILS) and intraepithelial (iTILS) in newly diagnosed early stage TNBC patients treated with two doses of MK-3475 prior to lumpectomy.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Effects of MK-3475 (Pembrolizumab) on the Breast Tumor Microenvironment in Triple Negative Breast Cancer
  • Official Title: Effects of MK-3475 (Pembrolizumab) on the Breast Tumor Microenvironment in Triple Negative Breast Cancer With and Without Intra-operative RT: a Window of Opportunity Study

Clinical Trial IDs

  • ORG STUDY ID: AAAQ7863
  • NCT ID: NCT02977468

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
Merck 3475 PembrolizumabKeytruda, SCH-900475, MK-3475Single Arm open label

Purpose

Assess response to MK-3475 in both primary tumor, normal breast stroma, circulating lymphocytes and serum exosomes in treatment naive triple negative breast cancer (TNBC) patients.

Assess for change in tumor-infiltrating lymphocytes (TILS) both stromal (sTILS) and intraepithelial (iTILS) in newly diagnosed early stage TNBC patients treated with two doses of MK-3475 prior to lumpectomy.

Detailed Description

This is an open-label, single-arm, single institution pre-operative "window of opportunity study" of pembrolizumab in subjects with newly diagnosed triple-negative, < 3 cm, node negative breast cancer. Subjects may not have received any prior neo/adjuvant chemotherapy, definitive surgery or radiation treatment prior to enrollment.

The goal of this project is to determine if immune modulation through treatment with MK-3475 (Pembrolizumab) in triple negative breast cancer (TNBC) patients will alter expression of immune tolerant markers [including PD-L1], within the primary tumor. Investigators hope to determine if MK-3475 exposure will change the molecular signature of breast stroma from "normal" adjacent breast tissue (non-tumor tissue) obtained prospectively at the time of breast conserving surgery (BCS) in TNBC patients. Finally, investigators will investigate how MK-3475 alters breast stromal response to high dose radiation delivered by intraoperative radiation therapy (IORT).

Trial Arms

NameTypeDescriptionInterventions
Single Arm open labelExperimentalParticipants receive 'Merck 3475 Pembrolizumab' by vein two weeks before Intraoperative radiation therapy (IORT). The Intrabeam® Photon Radiosurgery System is a miniature electron beam-driven X-ray source which provides a point source of low energy X-rays (50 kV maximum) at the tip of a 3.2 mm diameter tube. The radiation source can be inserted into the area of interest immediately after excision of the tumor and switched on for 20-35 minutes to provide intraoperative radiotherapy accurately targeted to the tissues that are at the highest risk of local recurrence. The dosimetric characteristics and early clinical applications of this device have been well studied and this is the device which was utilized in the international TARGIT trial.
  • Merck 3475 Pembrolizumab

    Eligibility Criteria

    Inclusion Criteria:

    1. Be willing and able to provide written informed consent/assent for the trial.

    2. Be > or = 21 years of age on day of signing informed consent.

    3. Histologically proven invasive breast carcinoma with triple negative receptor status (Estrogen receptor, Progesterone receptor and HER2 negative by IHC and FISH). Patients who are weekly positive for the estrogen or progesterone receptor (i.e., < or = 5%) are eligible.

    4. Clinically ≤ 3 cm unifocal lesion by imaging or physical examination.

    5. Clinically node negative, no evidence of metastatic disease.

    6. No prior chemotherapy, radiation therapy, or breast resection within 6 months of study entry.

    7. Breast size B cup or larger, to allow for IORT procedure.

    8. Have a performance status of 0 or 1 on the ECOG Performance Scale.

    9. Demonstrate adequate organ function.

    10. 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.

    11. 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.

    Exclusion Criteria:

    1. Multifocal disease within the breast.

    2. Has primary lesion > 3 cm in size radiographically or by physical examination. Pathologically proven nodal disease at diagnosis is not allowed.

    3. Has metastatic disease.

    4. Has a known additional malignancy that is progressing or requires active treatment in the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.

    5. Patients for whom radiotherapy for breast cancer is contraindicated because of medical reasons (e.g., connective tissue disorder or prior ipsilateral breast radiation).

    6. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.

    7. Has a known history of active TB (Bacillus Tuberculosis).

    8. Hypersensitivity to pembrolizumab or any of its excipients.

    9. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

    10. Has a History of (non-infectious) pneumonitis that required steroids or current pneumonitis.

    11. Has an active infection requiring systemic therapy.

    12. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

    13. Is pregnant or breastfeeding.

    14. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

    15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

    16. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).

    17. Has received a live vaccine within 30 days of planned start of study therapy.

    Maximum Eligible Age:80 Years
    Minimum Eligible Age:21 Years
    Eligible Gender:Female
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Number of subjects with signifcant mean percent change in TILs
    Time Frame:3 months
    Safety Issue:
    Description:This outcome measure is designed to determine if immune modulation therapy with MK-3475 will increase TILs in newly diagnosed TNBC tumors. The mean percent change in TILS in tumor tissue from initial core biopsy samples will be compared with pathology samples from definitive surgery after two cycles of MK-3475.

    Secondary Outcome Measures

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Eileen Connolly

    Trial Keywords

    • triple negative breast cancer
    • Pembrolizumab

    Last Updated

    November 28, 2016