Abraxane/Bevacizumab
Condition: Ovarian Cancer; Peritoneal Cancer
Intervention: Abraxane; Bevacizumab
Intervention description: Abraxane will be infused at a dose of 220 mg/m² in 20 mL normal saline per 100 mg vial over 30 minutes. This will follow the Bevacizumab infusion.; Bevacizumab will be infused at a dose of 10 mg/kg in 100 mL normal saline over 30 minutes ± 10 minutes. It is given first, prior to the Abraxane infusion.
Intervention MeSH terms: Bevacizumab; Albumin-Bound Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The protocol will study the effect of the combination of two drugs-Abraxane and
      Bevacizumab-on a subject's ovarian cancer, fallopian tube cancer, or primary peritoneal
      cancer. This study drug combination will be given to subjects who have already been treated
      for their cancer with other chemotherapy, and now their cancer has become worse or has come
      back again. Neither one of these study drugs has been approved by the FDA for treatment in
      these three types of cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed recurrent epithelial
             ovarian, fallopian tube or primary peritoneal carcinoma. Histologic documentation of
             the original primary tumor is required via the pathology report.

          -  All patients must have measurable disease. Measurable 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 >20mm when measured by conventional
             techniques including CT, and MRI, or >10 mm when measured by spiral CT.

          -  Patients must have at least one "target lesion" to be used to assess response as
             defined by RECIST. 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 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, high-dose therapy, consolidation, non-cytotoxic agents or extended therapy
             administered after surgical or non-surgical assessment.

          -  Patients are required to receive at least one additional cytotoxic regimen for
             management of recurrent or persistent disease. Patients are allowed to receive, but
             are not required to receive, biologic (non-cytotoxic) therapy either alone or as part
             of the cytotoxic regimens for management of recurrent or persistent disease.

          -  Age >18 years. Women all races and ethnic groups will be included.

          -  Patients with an ECOG performance status < 2. ( see APPENDIX A)

          -  Patients must have normal organ and marrow function as defined below:

          -  absolute neutrophil count >1,500/uL

          -  platelets >100,000/uL

          -  hemoglobin >9 g/dL

          -  total bilirubin within normal institutional limits

          -  AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal

          -  Alkaline Phosphatase within normal institutional limits

          -  creatinine <1.5 X institutional upper limit of normal

          -  Neurologic function: Neuropathy (sensory and motor) less than or equal to CTCAE v4.0
             grade 2. (see APPENDIX B)

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 28 days prior to entering
             the study or whose adverse events due to agents administered more than 28 days earlier
             continue to be grade 3 or greater.

          -  Patients may not have received any other investigational agents within the past 28
             days.

          -  Any hormonal therapy or immunotherapy directed at the malignant tumor must be
             discontinued at least one week prior to enrollment. Continuation of hormone
             replacement therapy is permitted. Continuation of other established medical treatments
             for a known medical condition is permitted.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to Abraxane or Bevacizumab.

          -  Patients who have had prior therapy with Abraxane.

          -  Patients who have received radiation to more than 25% of marrow-bearing areas. (see
             APPENDIX C)

          -  Patients with a history of other invasive malignancies, with the exception of
             non-melanoma skin cancer, are excluded if there is any evidence of other malignancy
             being present within the last five years.

          -  Patients who 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 five 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 five years prior to registration, and the patient remains free
             of recurrent or metastatic disease.

          -  Patients who have known active liver disease or hepatitis.

          -  Patients with active bleeding or pathologic conditions that carry high risk of
             bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major
             vessels.

          -  Patients with history or evidence upon physical examination of CNS disease, including
             primary brain tumor, seizures not controlled with standard medical therapy, any brain
             metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic
             attack (TIA) or subarachnoid hemorrhage within 6 months of the first date of treatment
             on this study.

          -  Patients with clinically significant cardiovascular disease, including:

        uncontrolled hypertension, myocardial infarction, unstable angina within 6 months of
        enrollment, NYHA Grade II or greater heart failure, serious cardiac arrhythmia requiring
        medication, grade II or greater peripheral vascular disease.

          -  Patients with clinically significant proteinuria. Patients with a urine protein of 1+
             on dipstick should undergo a 24-hour urine collection, which must demonstrate < 100 mg
             protein/24 hr to allow participation in the study.

          -  Patients with known hypersensitivity to Chinese hamster ovary cell products or other
             recombinant human or humanized antibodies.

          -  Patients who have a major surgical procedure, open biopsy, or significant traumatic
             injury within 28 days prior to enrollment on the study, or anticipation of need for
             major surgical procedure during the course of the study.

          -  Patients who have received commercial bevacizumab within 28 days prior to enrollment
             on the study.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection(with the exception of uncomplicated UTI), chronic non- healing wound, bone
             fracture, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Pregnant or lactating women are excluded from this study because of possible risk to
             the fetus or infant.

          -  Known HIV-positive patients are excluded from the study because of possible risk of
             lethal infection when treated with marrow suppressive therapy.

          -  Safety data regarding Abraxane use in patients with ascites is not available;
             therefore patients with symptomatic ascites will be excluded from participation in the
             study. Patients may have asymptomatic ascites.