Carboplatin, Nab-Paclitaxel and Pembrolizumab for Metastatic Triple-Negative Breast Cancer
Condition: Metastatic Triple Negative Breast Cancer
MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms
Intervention: Carboplatin; Nab-paclitaxel; Pembrolizumab
Intervention description: AUC 4.5 IV day 1 of 21-day cycle; 75mg/m2 IV days 1, 8 and 15 of 21-day cycle; 200 mg IV every 21 days
Intervention MeSH terms: Paclitaxel; Carboplatin; Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Carboplatin; Nab-Paclitaxel; Pembrolizumab

Summary:

      The purpose of this study is to see how effective the combination of the two chemotherapy
      drugs (carboplatin and nab-paclitaxel) are when added to a third drug, pembrolizumab.

      Pembrolizumab is an investigational (experimental) drug that works by reinvigorating the
      immune system, allowing it to target and destroy cancer cells. Pembrolizumab is experimental
      because it is not approved by the Food and Drug Administration (FDA) for this type of breast
      cancer treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must have histologically or cytologically confirmed metastatic triple
             negative breast cancer

          -  Subjects must have received no more than 2 prior therapies for this disease

          -  ECOG Performance Status 0-1

          -  Subjects must have normal organ and marrow function as defined below:

               -  Hemoglobin ≥ 10.0 g/dl

               -  Absolute neutrophil count ≥ 1,000/μL

               -  Platelet count ≥ 100,000/μL

               -  Total bilirubin within normal institutional limits

               -  AST (SGOT) ≤ 2.5 X institutional upper limit of normal

               -  ALT (SGPT) ≤ 2.5 X institutional upper limit of normal

               -  Serum creatinine ≤ 1.5 normal institutional limits

          -  Life expectancy of 12 weeks or more

          -  Subjects must have the ability to understand and the willingness to sign a written
             informed consent document

          -  Subjects must have measurable disease per RECIST v1.1

          -  Subjects must be willing to undergo a preliminary biopsy of a metastatic focus for
             research purposes. A second post-treatment biopsy will be offered but will not be
             mandated

        Exclusion Criteria:

          -  Prior treatment toxicities have not resolved to ≤ Grade 1 according to NCI CTCAE
             Version 4.0 (except for alopecia and neuropathy)

          -  Subjects receiving any other investigational agents

          -  Subjects with radiographically stable treated brain metastases are eligible but must
             not have been on steroid therapy for at least 4 weeks

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to nab-paclitaxel, carboplatin, pembrolizumab, or other agents used in
             this study

          -  Subjects with uncontrolled intercurrent illness including, but not limited to ongoing
             or active infection, symptomatic congestive heart failure, unstable angina pectoris,
             cardiac arrhythmia, or psychiatric illness/social situations that would limit
             compliance with study requirements

          -  Pregnant or breastfeeding women are excluded from this study

          -  Patients with conditions requiring immunosuppressive medications or chronic infections
             (including HIV infection, hepatitis B and C)

          -  Patients with chronic autoimmune disease

          -  Patients with prior therapy with antibodies that modulate T-cell function (e.g.,
             anti-PD-1, anti-PD-L1)

          -  Patients with evidence of active, non-infectious pneumonia

          -  Patients active infection requiring intravenous systemic therapy

          -  Patients with known psychiatric or substance abuse disorders that would interfere with
             cooperation with requirements of the trial

          -  Patients who have received a live vaccine within 30 days prior to the first dose of
             pembrolizumab

          -  Patients with a known additional malignancy that is progressing or requires active
             treatment (within the last 5 years). Exceptions: basal cell carcinoma of the skin,
             squamous cell carcinoma of the skin or in situ cervical cancer that has undergone
             potentially curative therapy

          -  Patients who have received monoclonal anti-cancer antibody within 4 weeks of first
             dose of study drugs

          -  Patients who have received chemotherapy, small molecule targeted therapy or radiation
             within the 2 weeks of first dose of study drugs

          -  Patients who have participated in MK-3475 Merck studies

          -  Patients with carcinomatous meningitis