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Pembrolizumab in Advanced BRCA-mutated Breast Cancer

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: NCT03025035
Recruitment Status : Recruiting
First Posted : January 19, 2017
Last Update Posted : March 8, 2019
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Monica Mita, Cedars-Sinai Medical Center

Brief Summary:
This trial will evaluate the use of immunotherapy in a population with incurable advanced breast cancer associated with a germline BRCA mutation. The main objective is to examine overall response rate of pembrolizumab (immunotherapy) single agent therapy in advanced BRCA-mutated breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Pembrolizumab Phase 2

Detailed Description:
There are two BRCA genes, BRCA1 and BRCA2, and they play a role in protecting cells from cancer. If one of these genes is mutated, cells may rapidly change and divide, which can lead to cancer. Pembrolizumab is a drug that works with the immune system to target the tumor (immunotherapy). The investigators want to know if pembrolizumab will be able to reduce the size and amount of cancer cells with fewer side effects than standard treatment by targeting the tumor.This research study is designed to test the investigational use of pembrolizumab in breast cancer.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open Label, Phase II Pilot Study of Immune Checkpoint Inhibition With Pembrolizumab in Advanced BRCA-mutated Breast Cancers
Actual Study Start Date : September 10, 2017
Estimated Primary Completion Date : January 30, 2020
Estimated Study Completion Date : January 30, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Pembrolizumab
This is an open-label, single-arm pilot study in 20 subjects with advanced BRCA mutation-associated breast cancer having progressed through at least a standard first line therapy.
Drug: Pembrolizumab
Pembrolizumab IV solution administered on Day 1 of each 3-week cycle
Other Names:
  • Keytruda
  • MK-3475

Primary Outcome Measures :
  1. Overall response rate (ORR) per RECIST1.1 [ Time Frame: Up to 2 years ]
    Defined as complete or partial response per RECIST 1.1 criteria with assessment every 6 weeks during the first year and while on the study drug, and every 9 weeks thereafter.

Secondary Outcome Measures :
  1. Progression free survival (PFS), per RECIST 1.1 [ Time Frame: Up to 2 years ]
    As measured by RECIST 1.1, in patients progressing after 1st line therapy

  2. Overall survival (OS) [ Time Frame: Up to 2 years ]
    Calculated in months from the start of treatment to the date of death from any cause

  3. Clinical Benefit Rate (CBR = CR+PR+SD) per RECIST 1.1 [ Time Frame: Up to 2 years ]
    As measured by RECIST 1.1, in patients progressing after 1st line therapy

  4. Duration of Response (DOR) for Complete Response (CR) and Partial Response (PR) per RECIST 1.1 [ Time Frame: Up to 2 years ]
    As measured by RECIST 1.1, in patients progressing after 1st line therapy

Other Outcome Measures:
  1. Exploratory: ORR based on immune-related (ir)RECIST [ Time Frame: Up to 2 years ]
    assessed by local investigator/local radiology.

  2. Exploratory: PFS based on immune-related (ir)RECIST [ Time Frame: Up to 2 years ]
    assessed by local investigator/local radiology.

  3. Exploratory: CBR based on immune-related (ir)RECIST [ Time Frame: Up to 2 years ]
    assessed by local investigator/local radiology.

  4. Exploratory: DOR based on immune-related (ir)RECIST [ Time Frame: Up to 2 years ]
    assessed by local investigator/local radiology.

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:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Be willing and able to provide written informed consent/assent for the trial
  • Be ≥18 years of age on day of signing informed consent
  • Advanced BRCA-mutated breast cancer progressing on or after prior therapy for metastatic disease or locally advanced disease; Prior therapy is defined as follows: for triple negative breast cancer - progressing after at least 1 line of any prior chemotherapy; for HER2 positive disease must have progressed after at least two HER2 directed therapies in the metastatic setting including ado-trastuzumab emtansine (T-DM1); for hormone receptor positive disease (ER, PR, or both) must have progressed after palbociclib plus hormonal therapy
  • Measurable disease by RECIST 1.1. Patients with non-measurable bone metastases in addition to measurable disease are eligible; however patients with non-measurable bone disease as the only site(s) of disease are not eligible.
  • ECOG 0, 1, or 2
  • Documented BRCA deleterious germline mutation. (While somatic mutations in BRCA 1 and 2 do occur, there is no standardized test for this biomarker, and subjects will be limited to germline carriers).
  • FFPE tumor tissue available for analysis
  • Adequate organ function
  • Female subject of childbearing potential should have a negative urine or serum pregnancy prior to study registration and re-tested 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 should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Exclusion Criteria:

  • Is currently participating or has participated in a study of investigational agent or using an investigational device with 30 days of the first dose of trial treatment.

    1. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 3 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
    2. Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
    3. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Is receiving systemic steroid therapy within three days prior to the first dose of initial treatment or receiving any other form of immunosuppressive medication
  • Is expected to require any other form of systemic or localized antineoplastic therapy while on trial.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). Has participated in another MK03475 trial.
  • Has known hypersensitivity to pembrolizumab or any of its excipients
  • Has a known additional malignancy that is progressing or requires active treatment. 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.
  • Has known history of prior malignancy except if the patient has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by MRI for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are using no steroids for at least three days prior to study medication.
  • Has evidence of interstitial lung disease or active, non-infectious pneumonitis
  • Has active tuberculosis
  • Has received a live vaccine within 30 days prior to the first dose of trial treatment.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Has an 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). Subjects with vitiligo or resolved childhood asthma/atopy would be exception to this rule. Subjects that require inhaled steroid or local steroid injections will not be excluded from the study. Subjects with hypothyroidism not from autoimmune disease and stable on hormone replacement will not be excluded from the study. Note: Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has had an allogenic tissue / solid organ transplant.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, 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 expecting to conceive or father children within the projected duration of the trial, starting with the screening visit (Visit 1) through 120 days after the last dose of pembrolizumab.

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): NCT03025035

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Contact: Emily Riffle 310-248-6733

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United States, California
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Parisa Mirzadehgan, MPH    310-967-4387   
Principal Investigator: Monica Mita, MD         
Sub-Investigator: Philomena McAndrew, MD         
Sub-Investigator: Heather McArthur, MD         
Sub-Investigator: Dorothy Park, MD         
Sub-Investigator: Greg Sarna, MD         
Sub-Investigator: Alain Mita, MD         
Sub-Investigator: Reva Basho, MD         
Sub-Investigator: Bobbie Rimel, MD         
Sponsors and Collaborators
Monica Mita
Merck Sharp & Dohme Corp.
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Principal Investigator: Monica Mita, MD Cedars-Sinal Medical Center

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Responsible Party: Monica Mita, Associate Professor of Medicine, Cedars-Sinai Medical Center Identifier: NCT03025035     History of Changes
Other Study ID Numbers: IIT2015-18-Mita-MK3475
First Posted: January 19, 2017    Key Record Dates
Last Update Posted: March 8, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Undecided

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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 Monica Mita, Cedars-Sinai Medical Center:
Immune checkpoint inhibition
Advanced BRCA-mutated breast cancer

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