Purpose

The main purpose of this study is to see if Pembrolizumab in combination with chemotherapy (carboplatin and gemcitabine) is safe and effective in treating patients with metastatic triple negative breast cancer. Pembrolizumab is a drug which may help the immune system to target and destroy cancer cells. Pembrolizumab has been approved by the FDA for the treatment of advanced melanoma and metastatic non-small cell lung cancer. However, it has not been approved as a treatment for breast cancer.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
Female
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Women diagnosed with pathologically confirmed metastatic triple negative invasive breast cancer (centrally confirmed immunophenotype negative for all three receptors ER, PR and HER2).
  • Have either evaluable disease, or have measurable clinical disease: Measurable disease, defined as at least 1 unidimensionally measurable lesion on a CT scan as defined by RECIST (version v1.1).
  • Patients received up to 2 prior regimens for their disease in the metastatic setting.
  • Patients are candidates for chemotherapy with carboplatin and gemcitabine.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
  • Patients must be willing and able to provide written informed consent for the trial
  • Demonstrate adequate organ function as defined below, all screening labs should be performed within 10 days of treatment initiation.
  • Absolute neutrophil count (ANC) Greater than or equal to 1,500 /mcL.
  • Platelets greater than or equal to 100,000 / mcL.
  • Hemoglobin greater than or equal to 9 g/dL or ≥ 5.6 mmol/L.
  • Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) less than or equal to 1.5 X upper limit of normal (ULN) OR greater than or equal to 60 mL/min for subject with creatinine levels greater than 1.5 X institutional ULN.
  • Serum total bilirubin less than 1.5 X ULN OR Direct bilirubin less than the ULN for subjects with total bilirubin levels greater than 1.5 ULN.
  • Aspartate aminotransferase (AST) (SGOT) and Alanine aminotransferase (ALT) (SGPT) less than or equal to 2.5 X ULN OR less than or equal to 5 X ULN for subjects with liver metastases.
  • International Normalized Ratio (INR) or Prothrombin Time (PT) less than or equal to 1.5 X ULN unless subject is receiving anticoagulant therapy.
  • Activated Partial Thromboplastin Time (aPTT) less than or equal to 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
  • Patients of childbearing potential must 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.

Exclusion Criteria

  • Patients participating in another trial of an investigational agent within 4 weeks of the first dose of the study.
  • Patients who received prior therapy using carboplatin/gemcitabine less than 12 months from the beginning of their enrollment or subjects whose tumor progressed while on treatment with carboplatin or cisplatin.
  • Patients with baseline grade 2 neuropathy.
  • Diagnosis of immunosuppression or receiving steroid therapy or other immunosuppressive therapy within 4 weeks of the study.
  • Active autoimmune disease or a documented history of autoimmune disease, or a syndrome that has required systemic treatment in the past 2 years
  • Has evidence of interstitial lung disease or active, non-infectious pneumonitis
  • Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 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.
  • If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Known additional malignancy that progressed and/or required treatment in the last 5 years. Except that for basal and squamous cell carcinoma of the skin or in situ cervical carcinoma that has completed potentially curative therapy.
  • Life expectancy of less than 3 months.
  • Prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death 1 ligand (PDL-1), anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte -associated antigen-4 (CTLA-4) antibody.
  • Pregnant, breastfeeding, or expecting to conceive children within the projected time of the trial, starting with the pre-screening or screening visit and through 120 days after the last dose of trial treatment.
  • Active infection requiring systemic 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 imaging 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 not using steroids for at least 7 days prior to trial treatment.
  • 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 received a live vaccine within 30 days prior to the first dose of trial treatment.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Pembrolizumab with Standard Chemotherapy
Pembrolizumab plus standard chemotherapy using carboplatin and gemcitabine.
  • Drug: Pembrolizumab
    IV Infusion of 200 mg given on day one of each 21 day treatment cycle.
    Other names:
    • MK-3475
    • Keytruda
  • Drug: Carboplatin
    IV infusion of a calculated dose (AUC 2 mL/min) given on days one and eight of each 21 day treatment cycle.
    Other names:
    • Paraplatin
  • Drug: Gemcitabine
    IV infusion of 800 mg/m^2 given on days one and eight of each 21 day treatment cycle.
    Other names:
    • Gemzar
Active Comparator
Standard Chemotherapy Alone
Standard chemotherapy alone using carboplatin and gemcitabine.
  • Drug: Carboplatin
    IV infusion of a calculated dose (AUC 2 mL/min) given on days one and eight of each 21 day treatment cycle.
    Other names:
    • Paraplatin
  • Drug: Gemcitabine
    IV infusion of 800 mg/m^2 given on days one and eight of each 21 day treatment cycle.
    Other names:
    • Gemzar

Recruiting Locations

Montefiore Medical Center
Bronx, New York 10467
Contact:
Sun Young, MD
suyoung@montefiore.org

More Details

NCT ID
NCT02755272
Status
Recruiting
Sponsor
Fox Chase Cancer Center

Study Contact

Elias Obeid, MD
215-728-2792
Elias.Obeid@fccc.edu

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.