Belinostat and Carboplatin in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer That Did Not Respond to Carboplatin or Cisplatin
Condition: Brenner Tumor; Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Primary Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer
MeSH terms: Adenocarcinoma; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial; Carcinoma, Endometrioid; Cystadenocarcinoma; Cystadenocarcinoma, Serous; Carcinoma; Cystadenocarcinoma, Mucinous; Brenner Tumor; Recurrence
Intervention: belinostat; carboplatin
Intervention description: Given IV; Given IV
Intervention MeSH terms: Carboplatin; Belinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving belinostat together with carboplatin works in
      treating patients with recurrent or persistent ovarian epithelial cancer, fallopian tube
      cancer, or primary peritoneal cancer that did not respond to carboplatin or cisplatin.
      Belinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell
      growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as
      carboplatin, work in different ways to stop the growth of tumor cells, either by killing the
      cells or by stopping them from dividing. Giving belinostat together with carboplatin may kill
      more tumor cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or
             primary peritoneal carcinoma; histologic documentation of the original primary tumor
             is required via the pathology report

          -  Patients with the following histologic epithelial cell types are eligible: Serous
             adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated
             carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell
             carcinoma, malignant Brenner's Tumor, or adenocarcinoma not otherwise specified
             (N.O.S.)

          -  All patients must have measurable disease as defined by RECIST 1.1; measureable
             disease is defined as at least one lesion that can be accurately measured in at least
             one dimension (longest dimension to be recorded); each lesion must be >= 10 mm when
             measured by CT, MRI or caliper measurement by clinical exam; or >= 20 mm when measured
             by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI

          -  Patients must have at least one "target lesion" to be used to assess response on this
             protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be
             designated as "non-target" lesions unless progression is documented or a biopsy is
             obtained to confirm persistence at least 90 days following completion of radiation
             therapy

          -  Patients must not be eligible for a higher priority GOG protocol, if one exists; in
             general, this would refer to any active GOG Phase III or Rare Tumor protocol for the
             same patient population

          -  Patients must have a GOG Performance Status of 0, 1, or 2

          -  Recovery from effects of recent surgery, radiotherapy, or chemotherapy

               -  Patients should be free of active infection requiring antibiotics (with the
                  exception of uncomplicated UTI)

               -  Any hormonal therapy directed at the malignant tumor must be discontinued at
                  least one week prior to registration; continuation of hormone replacement therapy
                  is permitted

               -  Any other prior therapy directed at the malignant tumor, including biological and
                  immunologic agents, must be discontinued at least three weeks prior to
                  registration

          -  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 non-cytotoxic
             therapy, intraperitoneal therapy, high-dose therapy, consolidation, or extended
             therapy administered after surgical or non-surgical assessment

          -  Patients must be considered platinum resistant or refractory according to the
             following criteria:

               -  Patients must have had progression of disease on or within 6 months of their last
                  platinum dose

               -  Progression of disease is defined according to RECIST 1.1

               -  The development of CA125 elevation on or within 6 months of last platinum
                  treatment, in the absence of radiographic progression according to RECIST 1.1, is
                  not considered platinum resistance for the purposes of this study

          -  Patients who have NOT received prior therapy with taxane-based chemotherapy MUST
             receive a second regimen that includes paclitaxel or docetaxel

          -  Patients must be considered paclitaxel-resistant, i.e., have had a treatment-free
             interval following paclitaxel of less than six months, or have progressed during
             paclitaxel-based therapy

          -  Patients must have NOT received any additional cytotoxic chemotherapy for management
             of recurrent or persistent disease, including retreatment with initial chemotherapy
             regimens except as noted above; (note: Optimal evaluation of the safety and efficacy
             of new chemotherapy regimens is best performed in patients with minimal prior therapy;
             non-investigational therapy, such as retreatment with platinum and/or paclitaxel, is
             non-curative in the setting of recurrent disease, and can generally be safely
             administered to patients following participation in a phase II trial)

          -  Patients are allowed to receive, but are not required to receive, one additional
             non-cytotoxic regimen for management of recurrent or persistent disease according to
             the following definition:

               -  Non-cytotoxic (biologic or cytostatic) agents include (but are not limited to)
                  monoclonal antibodies, cytokines, and small-molecule inhibitors of signal
                  transduction

          -  Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl, equivalent to the
             NCI Common Terminology Criteria (CTCAE v3.0) grade 1

          -  Platelets greater than or equal to 100,000/mcl

          -  Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN), per
             CTCAE v.3.0 grade 1

          -  Bilirubin less than or equal to 1.5 x ULN (CTCAE v.3.0 grade 1)

          -  SGOT (AST) less than or equal to 3 x ULN (per the CTCAE v.3.0 grade 1)

          -  Alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE v.3.0 grade 1)

          -  Neuropathy (sensory and motor) less than or equal to the CTCAE v3.0 grade 1

          -  Patients must have signed an approved informed consent and authorization permitting
             release of personal health information

          -  Patients must meet pre-entry requirements

          -  Patients of childbearing potential must have a negative serum pregnancy test prior to
             the study entry and be practicing an effective form of contraception

        Exclusion Criteria:

          -  Patients who have had prior therapy with Belinostat (PXD101) or other HDAC inhibitors

          -  Patients who have received radiation to more than 25% of marrow-bearing areas

          -  Patients with a history of other invasive malignancies, with the exception of
             non-melanoma skin cancer, and other specific malignancies as noted below, are excluded
             if there is any evidence of other malignancy being present within the last five years;
             patients are also excluded if their previous cancer treatment contraindicates this
             protocol therapy

          -  Patients who have received prior radiotherapy to any portion of the abdominal cavity
             or pelvis OTHER THAN for the treatment of ovarian cancer are excluded; prior radiation
             for localized cancer of the breast, head and neck, or skin is permitted, provided that
             it was completed more than three years prior to registration, and the patient remains
             free of recurrent or metastatic disease

          -  Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER
             THAN for the treatment of ovarian cancer are excluded; patients may have received
             prior adjuvant chemotherapy for localized breast cancer, provided that it was
             completed more than three years prior to registration, and that the patient remains
             free of recurrent or metastatic disease

          -  Patients must not use concomitant medications on PXD infusion days that may cause
             Torsade de Pointes; medications associated with this risk include:

               -  Amiodarone, Arsenic trioxide, Bepridil, Cisapride, Disopyramide, Dofetilide,
                  Droperidol, Erythromycin, Felbamate, Flecainide, Fluoxetine, Halofantrine,
                  Haloperidol, Ibutilide, Levofloxacin, Mesoridazine, Pentamidine, Procainamide,
                  Quinidine, Sotalol, Sparfloxacin, or Thioridazine

          -  Patients with significant cardiovascular disease defined as:

               -  Unstable angina pectoris, uncontrolled hypertension (blood pressure > 150/90
                  despite maximal medical therapy), congestive heart failure related to primary
                  cardiac disease, any condition requiring anti-arrhythmic therapy, ischemic or
                  severe valvular heart disease, or history of myocardial infarction within 6
                  months of trial entry

          -  Patients who are pregnant or nursing