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

NCT02977468 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: AAAQ7863
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Triple Negative Breast Cancer

Keywords

triple negative breast cancer; Pembrolizumab; IORT; tumor microenvironment

Outcome Measures

Primary Outcomes (1)

• Number of subjects with significant mean percent change in TILs

  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.

  3 months

Study Arms (1)

Single Arm open label

EXPERIMENTAL

Participants receive 'Merck 3475 Pembrolizumab' by vein one to two times 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.

Drug: Merck 3475 Pembrolizumab; Radiation: Intraoperative radiation therapy (IORT)

Interventions

Merck 3475 Pembrolizumab DRUG

Participants receive Pembrolizumab by vein over about 30 minutes on Day 1 of one to two cycles.

Also known as: Keytruda, SCH-900475, MK-3475

Single Arm open label

Intraoperative radiation therapy (IORT) RADIATION

Participants will receive Intraoperative radiation therapy (IORT) on the day of surgery.

Also known as: IORT, Zeiss Intrabeam

Single Arm open label

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• 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 IHC and FISH). Patients who are weekly positive for the estrogen or progesterone receptor (i.e., \< or = 10%) are eligible.
• Clinically ≤ 3 cm unifocal lesion by imaging or physical examination.
• Clinically node negative, no evidence of metastatic disease.
• No prior 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 ECOG Performance Scale.
• Demonstrate adequate organ function.
• 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.
• 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.

You may not qualify if:

• Multifocal disease within the breast.
• Has primary lesion \> 3 cm in size radiographically or by physical examination. Pathologically proven nodal disease at diagnosis is not allowed.
• Has metastatic disease.
• 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.
• Patients for whom radiotherapy for breast cancer is contraindicated because of medical reasons (e.g., connective tissue disorder or prior ipsilateral breast radiation).
• 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.
• Has a known history of active TB (Bacillus Tuberculosis).
• Has severe hypersensitivity (≥ Grade 3) to pembrolizumab or any of its excipients.
• 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.
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Has an active infection requiring systemic therapy.
• 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.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• 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.
• The effects of MK-3745 on the developing human fetus are unknown. For this reason and because monoclonal antibody neoplastic agents are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.

Sponsors & Collaborators

• Eileen Connolly: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (3)

Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Loyola University Chicago

Maywood, Illinois, 60153, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Eileen Connolly, MD

  Assistant Professor Of Radiation Oncology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eileen Connolly, MD

CONTACT

212-305-5050; epc2116@cumc.columbia.edu

Radiation Oncology Research Department

CONTACT

212-305-5050

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Radiation Oncology

Study Record Dates

• First Submitted: November 28, 2016
• First Posted: November 30, 2016
• Study Start: October 25, 2017
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2025
• Last Updated: June 20, 2024

Record last verified: 2024-06

Locations

US (3)