Pembrolizumab Combined With PLD For Recurrent Platinum Resistant Ovarian, Fallopian Tube Or Peritoneal Cancer
Condition: Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer
MeSH terms: Ovarian Neoplasms; Fallopian Tube Neoplasms; Peritoneal Neoplasms
Intervention: Pembrolizumab; Pegylated Liposomal Doxorubicin (PLD)
Intervention description: Please see "Arms" for description.; Please see "Arms" for description.
Intervention MeSH terms: Doxorubicin; Liposomal doxorubicin; Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Ovarian Cancer

Summary:

      This research study is studying the combination of Pegylated Liposomal Doxorubicin (PLD) and
      Pembrolizumab as a possible treatment for Recurrent Ovarian, Fallopian Tube or Peritoneal
      Cancer that is resistant to platinum therapy.

      The following interventions will be used in this study:

        -  Pegylated liposomal doxorubicin (PLD)

        -  Pembrolizumab
    

Eligibility criteria:

        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.

          -  Have measurable disease based on RECIST 1.1 criteria.

          -  Have a histologically confirmed diagnosis of epithelial ovarian cancer, fallopian tube
             or peritoneal cancer. All histologies of epithelial ovarian cancer are eligible except
             for carcinosarcomas.

          -  Patients must have had one prior platinum-based chemotherapeutic regimen for
             management of primary disease containing carboplatin, cisplatin, or another
             organoplatinum compound. This initial treatment may have included intraperitoneal
             therapy, consolidation, biologic/targeted (non-cytotoxic) agents (e.g., bevacizumab)
             or extended therapy administered after surgical or non-surgical assessment.

          -  Patients must have platinum resistant cancer with a platinum free interval of < 6
             months. Progression after last platinum is based on investigator assessment.

          -  Patients are allowed to receive, but are not required to receive, up to two additional
             cytotoxic regimens for management of recurrent or persistent disease, with no more
             than 1 non-platinum, non-taxane regimen.

          -  Patients are allowed to receive, but are not required to receive, biologic/targeted
             (non-cytotoxic) therapy as part of their primary treatment regimen. For the purposes
             of this study, Poly (ADP-ribose) polymerase (PARP) inhibitors will be considered
             "cytotoxic." Patients are allowed to receive, but are not required to receive, PARP
             inhibitors for management of primary or recurrent/persistent disease (either alone or
             in combination with cytotoxic chemotherapy). Single agent hormonal therapies will not
             be counted as a line of treatment.

          -  Have adequate tissue from an archived specimen of ovarian cancer (between 10 to 15
             slides of unstained tumor).

          -  Have a performance status of 0 or 1 on the ECOG Performance Scale (Appendix A).

          -  Demonstrate adequate organ function as defined in Table 1, all screening labs must be
             performed within 10 days of treatment initiation.

        Table 1 Adequate Organ Function Laboratory Values

        System Laboratory Value

          -  Hematological

               -  Absolute neutrophil count (ANC) ≥1,500 /mcL

               -  Platelets ≥100,000 / mcL

               -  Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7
                  days of assessment)

          -  Renal

               -  Serum creatinine OR

               -  Measured or calculated creatinine clearance (GFR can also be used in place of
                  creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for
                  participant with creatinine levels > 1.5 X institutional ULN

          -  Hepatic

               -  Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for participants with
                  total bilirubin levels > 1.5 ULN

               -  AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for participants with liver
                  metastases

               -  Albumin >2.5 mg/dL

          -  Coagulation

               -  International Normalized Ratio (INR) or Prothrombin Time (PT)

               -  Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless participant is
                  receiving anticoagulant therapy as long as PT or PTT is within therapeutic range
                  of intended use of anticoagulants ≤1.5 X ULN unless participant is receiving
                  anticoagulant therapy as long as PT or PTT is within therapeutic range of
                  intended use of anticoagulants aCreatinine clearance should be calculated per
                  institutional standard.

          -  Female participants of childbearing potential must have a negative serum pregnancy
             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 participants 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.
             Participants 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 a 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.

          -  Patients cannot have primary platinum refractory cancer, i.e. documented cancer
             progression while receiving platinum or within one month of receipt of a platinum
             based regimen.

          -  Has received a prior anthracycline chemotherapy either for ovarian cancer treatment or
             another previous malignancy.

          -  Left ventricular ejection fraction (LVEF) defined by multigated acquisition (MUGA) or
             echocardiogram which is below the institutional lower limit of normal prior to
             starting study treatment.

          -  Has a known history of active TB (Bacillus Tuberculosis)

          -  Hypersensitivity to pembrolizumab or any of its excipients and/or liposomal
             doxorubicin.

          -  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: Participants with < Grade 2 neuropathy are an exception to this criterion
                  and may qualify for the study.

               -  Note: If participant underwent major surgery, they must have recovered adequately
                  from the toxicity and/or complications from the intervention prior to starting
                  therapy.

          -  Has a known additional malignancy that is progressing or requires active treatment. In
             addition, patients cannot have been diagnosed with another malignancy within 3 years
             of starting 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. Participants 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 clinically active and significant 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 (eg., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

          -  Has known history of, or any evidence of active, non-infectious 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 participant's
             participation for the full duration of the trial, or is not in the best interest of
             the participant 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 within the projected duration
             of the trial, starting with the pre-screening or 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).

          -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

          -  Has received a live vaccine within 30 days of planned start of study therapy.

          -  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.