Belinostat in Treating Patients With Advanced Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer or Ovarian Low Malignant Potential Tumors
Condition: Fallopian Tube Carcinoma; Primary Peritoneal Carcinoma; Recurrent Borderline Ovarian Surface Epithelial-Stromal Tumor; Recurrent Ovarian Carcinoma; Stage III Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage III Ovarian Cancer; Stage IV Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage IV Ovarian Cancer
MeSH terms: Carcinoma; Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Brenner Tumor; Recurrence
Intervention: Belinostat; Laboratory Biomarker Analysis
Intervention description: Given IV; Correlative studies
Intervention MeSH terms: Belinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well belinostat works in treating patients with ovarian
      epithelial cancer, primary peritoneal cancer, or fallopian tube cancer that have spread to
      other places in the body or ovarian low malignant potential tumors. Belinostat may stop the
      growth of tumor cells by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically/cytologically confirmed ovarian epithelial cancer, primary peritoneal
             carcinoma or fallopian tube cancer that recurred despite initial platinumbased therapy
             OR micropapillary/borderline (Low Malignant Potential) tumors of ovary

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded) as >=
             20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT)
             scan

          -  Patients in the platinum resistant (progression within 6 months of platinum based
             therapy) group: must have had no more than a total of 3 prior chemotherapy regimens;
             at least one prior regimen will have contained a platinum agent (carboplatin or
             cisplatin)

          -  Patients with micropapillary or borderline (LMP) tumors: must have had no more than a
             total of 3 prior chemotherapy regimens

          -  Patients must have completed any prior chemotherapy, radiotherapy or surgery at least
             4 weeks (at least 6 weeks for nitrosureas and mitomycin C) before study entry and
             patients must have recovered from the toxic effects from any prior therapy; patients
             must not have had more than 40% of their bone marrow radiated and must have either
             measurable disease outside the field or progression post radiation therapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

          -  Leukocytes >= 3.0 x 10^9/L

          -  Absolute neutrophil count >= 1.5 x 10^9/L

          -  Platelets >= 100 x 10^9/L

          -  Total bilirubin =< institutional upper limit of normal

          -  Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/
             alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X
             institutional upper limit of normal

          -  Creatinine =< institutional upper limit of normal OR creatinine clearance >= 60
             mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

          -  Biopsies are not mandatory but patients will be asked to undergo tumor biopsy once
             before and once during experimental therapy if considered medically safe for them to
             do so; patients must be willing to have the peripheral blood mononuclear cell (PBMC)
             procured prior to and during the treatment

          -  Eligibility of patients receiving any medications or substances known to affect or
             with the potential to affect the activity or pharmacokinetics of PXD101 will be
             determined following review of their case by the Principal Investigator; efforts
             should be made to switch patients who are taking enzyme-inducing anticonvulsant agents
             to other medications

          -  Women of child-bearing potential and their partners must agree to use adequate
             contraception (hormonal or barrier method of birth control; abstinence) prior to study
             entry and for the duration of study participation; should a woman become pregnant or
             suspect she is pregnant while participating in this study, she should inform her
             treating physician immediately

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier

          -  A marked baseline prolongation of QT/corrected QT (QTc) interval, e.g., repeated
             demonstration of a QTc interval > 500msec; long QT syndrome; the required use of
             concomitant medication on PXD101 infusion days that may cause Torsade de Pointes
             (disopyramide, dofetilide, ibutilide, procainamide, quinidine, sotalol, bepridil,
             amiodarone, arsenic trioxide, cisapride, lidoflazine, clarithromycin, erythromycin,
             halofantrine, pentamidine, sparfloxacin, domperidone, droperidol, chlorpromazine,
             haloperidol, mesoridazine, thioridazine, pimozide & methadone)

          -  Significant cardiovascular disease including unstable angina pectoris, uncontrolled
             hypertension, congestive heart failure related to primary cardiac disease, a condition
             requiring anti-arrythmic therapy, ischemic or severe valvular heart disease, or a
             myocardial infarction within 6 months prior to the trial entry

          -  Patients may not be receiving any other investigational agents

          -  Patients with known brain metastases should be excluded from this clinical trial

          -  History of allergic reactions attributed to sulfonamides, arginine and compounds of
             similar chemical or biologic composition to PXD101

          -  Patients should not have taken valproic acid, another histone deacytelase inhibitor,
             for at least 2 weeks prior to enrollment

          -  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

          -  Patients with bowel obstruction would not be eligible because of compromised
             functional status unless they are on parenteral support

          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if
             the mother is treated with PXD101

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible