A Study of Pembrolizumab With Standard Treatment in Patients With Recurrent Platinum-resistant Ovarian Cancer
Condition: Ovarian Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Intervention: Pembrolizumab; Gemcitabine; Cisplatin
Intervention description: Pembrolizumab IV solution; Gemcitabine IV solution; Cisplatin IV solution
Intervention MeSH terms: Gemcitabine; Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: immunotherapy; platinum-resistant ovarian cancer; immune checkpoint inhibitors

Summary:

      To evaluate the efficacy and safety of anti-PD-1 antibody MK-3475 (pembrolizumab) in
      combination with gemcitabine and cisplatin chemotherapy in women with recurrent
      platinum-resistant ovarian cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Be willing and able to provide written informed consent/ for the trial.

          -  Be at least 18 years of age on day of signing informed consent.

          -  Have histologically confirmed diagnosis of recurrent epithelial ovarian, peritoneal or
             fallopian tube carcinoma that has progressed within 6 months of prior cytotoxic
             chemotherapy. Histologic confirmation of the primary tumor by review of the pathology
             report is required. Patients must have had at least one prior platinum-based
             chemotherapeutic regimen. Initial treatment may have been administered as an
             intraperitoneal, intravenous or dose-dense regimen. Progression within 6 months of a
             non-platinum containing regimen is eligible if the patient is considered
             platinum-resistant to the last platinum-containing regimen. Patients who have received
             prior cisplatin and gemcitabine treatment are eligible to participate.

          -  Have measurable disease based on RECIST 1.1

          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale.

          -  Demonstrate adequate organ function, all screening labs should be performed within 28
             days of treatment initiation.

          -  Female subject of childbearing potential should have a negative urine or serum
             pregnancy test 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. Patients who have had prior hysterectomy and/or bilateral
             oophorectomy are not required to have a pregnancy test.

          -  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.

        Exclusion Criteria:

          -  Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy or used an investigational
             device within 4 weeks of the first dose of treatment.

          -  Has diagnosis of immunodeficiency or is receiving systemic steroid therapy 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)

          -  Hypersensitivity to pembrolizumab or any of its excipients. Has had a prior
             anti-cancer monoclonal antibody (mAb) 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.

        Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify
        for the study.

        Note: If subject received major surgery including (curative or palliative surgery), they
        must have recovered adequately from the toxicity and/or complications from the intervention
        prior to starting therapy.

        Note: Patients who have hypertension as an adverse event related to prior angiogenesis
        targeted therapy may be allowed if ≤ Grade 2 and considered by investigator to be
        well-controlled on anti-hypertensive agents.

          -  Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer.

          -  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. This exception does not include
             carcinomatous meningitis which is excluded regardless of clinical stability.

          -  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 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 children within the projected
             duration of the trial, starting with screening visit through 120 days after the last
             dose of trial treatment.

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

          -  Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) or
             positive serum test for HIV as per testing at screening

          -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected) as per test at screening

          -  Has received a live vaccine within 30 days of planned start of study therapy. Note:
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
             attenuated vaccines, and are not allowed.