Dose Dense Paclitaxel With Pembrolizumab (MK-3475) in Platinum Resistant Ovarian Cancer
Condition: Ovarian Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Intervention: Pembrolizumab; Paclitaxel
Intervention description: Pembrolizumab: 200 mg, every (Q) 3 weeks, via intravenous (IV) infusion, until progression or toxicity (or up to 24 months). The first cycle will begin on day 8.; Paclitaxel: 80 mg/m^2, Q week for 3 weeks, via IV infusion, until progression or toxicity (or complete response if at least 6 cycles, at the discretion of the investigator and participant). Cycle 1 will have an extra lead in week (4 weeks total) with Paclitaxel only on week 1.
Intervention MeSH terms: Paclitaxel; Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: platinum resistant; recurrent; persistent; epithelial; ovarian; fallopian tube; primary peritoneal; carcinoma

Summary:

      The purpose of this study is to find out if the combination of Paclitaxel once per week with
      Pembrolizumab once every 3 weeks will help participants with this disease. Researchers want
      to find out the effectiveness of the drug combination to improve the delay of cancer
      progression or death and compare it to historical data for weekly paclitaxel alone, and
      assess safety.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Must have confirmation of the histologic diagnosis of high-grade (grade 2-3)
             epithelial, non-mucinous, non-borderline, ovarian, fallopian tube, or primary
             peritoneal carcinoma. May be based on original pathology report or review of original
             slides.

          -  Willing and able to provide written informed consent/assent and authorization

          -  ≥ 18 years of age on day of signing informed consent

          -  Disease must have been persistent or have recurred within 6 months of prior platinum
             therapy. Disease may not have progressed during prior platinum therapy (i.e.,
             refractory).

          -  Have measurable disease or detectable (non-measureable) disease

          -  Measurable disease: must have at least one "target lesion" to be used to assess
             response on this protocol.

          -  Prior Therapy:

               -  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, non-cytotoxic agents (biologic/ targeted) or extended therapy
                  administered after surgical or non-surgical assessment. If patients were treated
                  initially with paclitaxel for their primary disease, this can have been given
                  weekly or every 3 weeks. The most recent therapy and any therapies subsequent to
                  initial therapy, however, cannot have contained weekly paclitaxel. If the
                  immediate prior (most recent therapy) is the initial therapy, it may not have
                  been with weekly paclitaxel.

               -  Allowed to receive (not required to receive), 2 additional cytotoxic regimens for
                  management of recurrent or persistent disease, with no more than 1 non-platinum
                  regimen. Treatment with weekly paclitaxel for recurrent or persistent disease is
                  NOT allowed.

               -  Allowed to receive(not required to receive), non-cytotoxic (biologic/targeted)
                  therapy as part of their primary treatment regimen. Allowed to receive (not
                  required to receive), non-cytotoxic (biologic/targeted) therapy as part of their
                  treatment for recurrent or persistent disease and/or as treatment for recurrent
                  or persistent disease. If non-cytotoxic (biologic/targeted) therapy is given
                  alone (i.e., not in combination with cytotoxic chemotherapy) it will NOT count as
                  a prior regimen.

          -  Have tissue from an archival tissue sample that has been identified and confirmed as
             available for study, or newly obtained core or excisional biopsy of a tumor lesion

          -  Have received 1 prior regimen must have an Eastern Cooperative Oncology Group (ECOG)
             Performance Status of 0, 1, or 2. If have received 2 or 3 prior regimens, must have an
             ECOG Performance Status of 0 or 1.

          -  Adequate organ function as defined in the protocol

          -  Recovery from effects of recent surgery, radiotherapy, or chemotherapy: Should be free
             of active infection requiring antibiotics (with exception of uncomplicated UTI); Any
             hormonal therapy directed at the malignant tumor must be discontinued at least 2 weeks
             prior to registration (continuation of hormone replacement therapy is permitted); Any
             other prior therapy directed at the malignant tumor, including chemotherapy,
             biologic/targeted and immunologic agents, must be discontinued at least 2 weeks prior
             to registration and at least 3 weeks before day 1 on trial.

          -  Women of Childbearing Potential (WOCBP): Negative urine or 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.

          -  WOCBP 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:

          -  Have low-grade or non-epithelial cancers, mucinous cancers, and/or borderline
             low-malignant potential cancers

          -  Currently participating in/have participated in a study of an investigational agent or
             is or has been using an investigational device within 4 weeks of the first dose of
             treatment

          -  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

          -  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 prior therapies

          -  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. - Note: If received major
             surgery, must have recovered adequately from the toxicity and/or complications from
             the intervention prior to starting therapy.

          -  History of other invasive malignancies (with exception of non-melanoma skin cancer and
             or in situ cancers that have undergone potentially curative therapy) are excluded if
             there is any evidence of other malignancy being present within the last 3 years.
             Patients are also excluded if their previous cancer treatment contraindicates this
             protocol therapy.

          -  Have received prior radiotherapy to any portion of the abdominal cavity or pelvis
             OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer
             within the last 3 years are excluded. Prior radiation for localized cancer of the
             breast, head and neck, or skin is permitted, provided that it was completed more than
             3 years prior to registration, and the patient remains free of recurrent or metastatic
             disease.

          -  Have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the
             treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last 3
             year. May have received prior adjuvant chemotherapy for localized breast cancer,
             provided that it was completed more than 3 years prior to registration, and the
             patient remains free of recurrent or metastatic disease.

          -  History of synchronous endometrial cancer unless all of the following conditions are
             met: Stage not greater than I-A (FIGO 2010 staging criteria); no more than superficial
             myometrial invasion (<50%), without vascular or lymphatic invasion; no poorly
             differentiated subtypes, including papillary serous, clear cell or other FIGO Grade 3
             lesions and it has been greater than 3 years since diagnosis and there have been no
             recurrences.

          -  Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
             Patients with previously treated brain metastases may participate provided they are
             stable (without evidence of progression by imaging for at least 4 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.

          -  Active autoimmune disease that has required systemic treatment in 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..

          -  Evidence of interstitial lung disease, any active, non-infectious pneumonitis, or
             known active tuberculosis

          -  An active infection requiring systemic therapy

          -  History or current evidence of any condition, therapy, or laboratory abnormality that
             might confound the results of the trial, interfere with participation for the full
             duration of the trial, or is not in the best interest of the participant, in the
             opinion of the treating physician or the principal or study investigator.

          -  Known psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the trial

          -  Pregnant or breastfeeding, or expecting to conceive children 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.

          -  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

          -  Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)

          -  Known active Hepatitis B or Hepatitis C

          -  Received a live vaccine within 30 days prior to the first dose of trial treatment

          -  Peripheral neuropathy Common Terminology Criteria for Adverse Events (CTCAE) grade 2
             or higher

          -  Known hypersensitivity to pembrolizumab or any of its excipients

          -  Known hypersensitivity to paclitaxel

          -  Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis.