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Breast Cancer Study of Preoperative Pembrolizumab + Radiation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03366844
Recruitment Status : Recruiting
First Posted : December 8, 2017
Last Update Posted : November 19, 2018
Information provided by (Responsible Party):
Stephen Shiao, Cedars-Sinai Medical Center

Brief Summary:

This study is being done to assess the safety and tolerability of pembrolizumab (study drug) combined with standard radiation to the tumor (tumor boost) before patients undergo standard treatment that can consist of one or more of the following: breast-conserving surgery, radiation to the entire breast/chest wall after surgery, and chemotherapy.

Study participants will receive two doses of the study drug intravenously (through the vein) before their planned breast surgery or chemotherapy. The study drug will be administered three weeks apart. At the time of the second dose, radiation to the tumor in the affected breast will be given. This type of radiation treatment is called a "tumor boost", which is a standard part of radiation therapy for breast cancer that may occur either before or after planned breast-conserving surgery. Patients will receive breast surgery or begin chemotherapy approximately six weeks after your first dose of the study drug.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Pembrolizumab Radiation: RT Boost Early Phase 1

Detailed Description:

With more than 1 million new cases diagnosed yearly worldwide, breast cancer is a global public health burden. Over the past decade, molecular subtyping of breast cancer has identified intrinsic subtypes that may be at enhanced risk for both local and distant recurrence. This study focuses on the immunogenicity of high-risk breast cancer subtypes that are likely to display a dense lymphocytic infiltration including including TNBC and HR+/HER2- tumors.

Immune build up via immune co-stimulatory molecules permits the ensuing immune response to strengthen and destroy cancer systemically. Thus, the effect of the anti-tumor immune response initiated by the radiation to an intact tumor by combination with checkpoint blockade is increased.

Pembrolizumab is an optimal immunotherapy agent to study, as this agent has recently been FDA approved for use in multiple tumor types. It is therefore ready to be tested for efficacy in other disease sites and in combination with other treatments.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Intervention Model Description:

Single Arm with Two Cohorts

  1. Cohort 1: High-risk, ER-positive and HER2-negative breast cancer patients with primary tumors measuring at least 2cm
  2. Cohort 2: TNBC patients with primary tumors measuring at least 2cm
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of the Preoperative Combination of Pembrolizumab and Radiation Therapy in Patients With Operable Breast Cancer
Actual Study Start Date : December 22, 2017
Estimated Primary Completion Date : December 30, 2019
Estimated Study Completion Date : December 30, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Pembrolizumab with RT Boost
Study drug plus "tumor boost" before standard of care treatment
Drug: Pembrolizumab
checkpoint inhibitor
Other Names:
  • Keytruda
  • MK-3475

Radiation: RT Boost
The second dose of pembrolizumab will be given in conjunction with an RT boost, consisting of 8 Gy for 3 fractions.

Primary Outcome Measures :
  1. Number of patients who do not necessitate a delay in standard of care treatment after receiving the investigational combination of preoperative Pembrolizumab and radiation [ Time Frame: 8 weeks after trial initiation ]
    Safety/tolerability of preoperative radiation and Pembrolizumab in newly diagnosed, non-metastatic patients with triple negative breast cancer.

  2. Changes in Tumor Infiltrating Lymphocytes (TIL) [ Time Frame: 8 weeks after trial initiation ]
    An increase in the tumor-infiltrating lymphocyte score as measured by Salgado criteria

Secondary Outcome Measures :
  1. Pembrolizumab-related adverse events [ Time Frame: 15 weeks after trial initiation ]
    Treatment toxicities

  2. Immune-related adverse events [ Time Frame: 15 weeks after trial initiation ]
    Treatment toxicities

  3. Invasive disease-free survival after preoperative radiation and Pembrolizumab [ Time Frame: From treatment start date until date of documented recurrence or death from breast cancer, assessed up to 19 weeks after start of treatment ]
    Disease-free survival, as described from time from occurrence of surgery to time from first recurrence from or death from breast cancer

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Confirmed histologic diagnosis of invasive adenocarcinoma of the breast, and
  • ER, PR and HER2 testing (on outside or Cedars-Sinai biopsy report), and

    • High-risk, ER-positive and HER2-negative breast cancer patients. ER-positive disease is defined as ER>10%, any PR and HER2-negative by ASCO CAP guidelines. High-risk disease will be defined by the presence of at least 2 of the following 3 criteria: histologic grade II-III, Ki-67 > 20%, ER expression < 75% by IHC)
    • TNBC patients (defined as ER<10%, PR<10%, HER2-neu 0-1+ by IHC or FISH-negative; or as per MD discretion)
  • Operable tumor measuring ≥2 cm in maximal diameter as measured by any available standard of care imaging (mammogram, breast ultrasound, breast MRI)
  • Any nodal status
  • Multifocal disease is permitted; largest focus must measure ≥2 cm
  • Synchronous bilateral invasive breast cancer is permitted
  • No indication of distant metastases
  • Breast-conserving therapy is planned
  • Tumor amenable to preoperative radiation therapy boost as determined by radiation oncologist
  • ECOG performance status score of 0 or 1
  • Screening laboratory values must meet the following criteria:

    i. White blood cells (WBCs) ≥ 2000/μL ii. Absolute neutrophil count (ANC) ≥ 1500/μL iii. Platelets ≥ 100 x 103/μL iv. Hemoglobin ≥ 11.0 g/dL v. Serum creatinine ≤ 2 mg/dL (or glomerular filtration rate ≥ 40 ml/min) vi. AST ≤ 2.5 x upper limit of normal (ULN) vii. ALT ≤ 2.5 x ULN viii. Bilirubin within normal limits (except subjects with Gilbert's syndrome, who must have total bilirubin < 3.0 mg/dL) ix. Negative HIV screening test x. Negative screening tests for Hepatitis B and Hepatitis C.

Patients with positive results that do not indicate true active or chronic infection may enroll after discussion and consensus agreement by the treating physician and principal investigator.

  • Women of childbearing potential (WOCBP) must be using an acceptable method of contraception to avoid pregnancy throughout the study and for at least 4 months after the last dose of pembrolizumab in such a manner that the risk of pregnancy is minimized. See below for the definition of WOCBP.
  • WOCBP must have a negative serum pregnancy test within 14 days prior to the first dose of pembrolizumab.
  • Women must not be breastfeeding.
  • Willingness to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.
  • Willingness to undergo mandatory Week 4 research biopsy
  • Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.

Exclusion Criteria:

  • HER2-positive breast cancer defined as IHC3+ or IHC2+ with FISH>2 AND copy number >4 OR FISH <2 AND copy number >6
  • Inflammatory breast cancer
  • Contraindication(s) to breast-conserving therapy
  • Contraindication to radiation therapy or planned partial breast irradiation
  • Patients with cosmetic breast augmentations, specifically sub glandular implants with altered breast tissue, at the time of diagnosis
  • Medical history and concurrent diseases

    • Subjects with active, known or suspected autoimmune disease. Subjects 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.
    • Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
    • Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
    • Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Prohibited Treatments and/or Therapies

    • Chronic use of immunosuppressants and/or systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses). However, use of corticosteroids is allowed for the treatment of immune related Adverse Events (irAEs), or adrenal insufficiency.
    • Any non-oncology vaccine therapy used for prevention of infectious diseases within 4 weeks prior to first dose of pembrolizumab.
    • Prior treatment with pembrolizumab or other PD-1/PD-L1 inhibitor.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03366844

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Contact: Cindi Martin 310-423-2276

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United States, California
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Lindsey Ristow, MPH    310-248-8617   
Sub-Investigator: Monica Mita, MD         
Sub-Investigator: Reva Basho, MD         
Sub-Investigator: Heather McArthur, MD         
Sub-Investigator: Stephen Shiao, MD         
Sub-Investigator: Armando Giuliano, MD         
Sub-Investigator: Amin Mirhadi, MD         
Sub-Investigator: Mitchell Kamraya, MD         
Sub-Investigator: Michele Burnison, MD         
Sub-Investigator: Farin Amersi, MD         
Sub-Investigator: Catherine Dang, MD         
Sub-Investigator: Scott Karlan, MD         
Sub-Investigator: Alice Chung, MD         
Sub-Investigator: Cathie Chung, MD         
Sub-Investigator: Dorothy Park, MD         
Sub-Investigator: Michael Van Scoy-Moser, MD         
Sponsors and Collaborators
Stephen Shiao
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Principal Investigator: Stephen Shiao, MD, PHD Cedars-Sinai Medical Center

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Responsible Party: Stephen Shiao, Associate Professor of Radiation Oncology and Medicine, Cedars-Sinai Medical Center Identifier: NCT03366844     History of Changes
Other Study ID Numbers: IIT2017-07-HO-PembroRT
First Posted: December 8, 2017    Key Record Dates
Last Update Posted: November 19, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Stephen Shiao, Cedars-Sinai Medical Center:
invasive adenocarcinoma of the breast
ER-positive and HER2-negative breast cancer
Triple negative breast cancer (TNBC)
checkpoint inhibitor

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents