RECRUITING

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

Conditions

Triple Negative Breast Cancer Pembrolizumab IORT tumor microenvironment

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

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.

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

Quick Facts

Study Start:2017-10-25

Study Completion:2025-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT02977468

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:21 Years to 80 Years

Sexes Eligible for Study:FEMALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Be willing and able to provide written informed consent/assent for the trial. 2. Be ≥ 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 = 10%) 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 anti-cancer therapy including investigational agents, 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.	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, DCIS of the breast, 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 chronic systemic steroid therapy (in dosing exceeding 10mg daily of prednisone equivalent) 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. Has severe hypersensitivity (≥ Grade 3) 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 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. 13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 14. Is pregnant or breastfeeding, or expected to conceive children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment. 15. 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). 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. 18. Has a medical history of allogenic stem cell transplant 19. Has received a solid organ transplant 20. Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV testing is required unless mandated by local health authority.

Inclusion Criteria

Exclusion Criteria

1. Be willing and able to provide written informed consent/assent for the trial.
2. Be ≥ 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 = 10%) 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 anti-cancer therapy including investigational agents, 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.

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, DCIS of the breast, 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 chronic systemic steroid therapy (in dosing exceeding 10mg daily of prednisone equivalent) 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. Has severe hypersensitivity (≥ Grade 3) 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 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.
13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
14. Is pregnant or breastfeeding, or expected to conceive children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
15. 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).
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.
18. Has a medical history of allogenic stem cell transplant
19. Has received a solid organ transplant
20. Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV testing is required unless mandated by local health authority.

Contacts and Locations

Study Contact

Eileen Connolly, MD

CONTACT

212-305-5050

epc2116@cumc.columbia.edu

Radiation Oncology Research Department

CONTACT

212-305-5050

Principal Investigator

Eileen Connolly, MD

PRINCIPAL_INVESTIGATOR

Assistant Professor Of Radiation Oncology

Study Locations (Sites)

Emory University

Atlanta, Georgia, 30322

United States

Loyola University Chicago

Maywood, Illinois, 60153

United States

Columbia University Irving Medical Center

New York, New York, 10032

United States

Collaborators and Investigators

Sponsor: Eileen Connolly

Eileen Connolly, MD, PRINCIPAL_INVESTIGATOR, Assistant Professor Of Radiation Oncology

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2017-10-25

Study Completion Date2025-12-31

Study Record Updates

Study Start Date2017-10-25

Study Completion Date2025-12-31

Terms related to this study

Keywords Provided by Researchers

triple negative breast cancer
Pembrolizumab
IORT
tumor microenvironment

Additional Relevant MeSH Terms

Triple Negative Breast Cancer