Sequential Angiogenic Blockade for the Treatment of Recurrent Mullerian Malignancies
Condition: Ovarian Cancer; Peritoneal Cancer; Fallopian Tube Cancer
MeSH terms: Neoplasms; Fallopian Tube Neoplasms
Intervention: Bevacizumab; Cyclophosphamide
Intervention MeSH terms: Cyclophosphamide; Bevacizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: avastin; bevacizumab; cyclophosphamide; cytoxan; mullerian malignancies

Summary:

      The goals of this study were to evaluate the efficacy and safety of sequentially blocking the
      angiogenesis pathway via known antiangiogenic mechanisms, first with bevacizumab and then
      addition of oral cyclophosphamide upon progression of cancer through bevacizumab. The drugs
      used in this study were chosen because of their known antiangiogenic properties,
      tolerability, and anti-ovarian cancer effects.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of epithelial ovarian cancer, primary peritoneal
             cancer, or fallopian tube cancer.

          -  Recurrent cancer and have received and failed a previous platinum-based chemotherapy
             regimen.

          -  Up to 2 prior lines of chemotherapy in the recurrent setting (either platinum-based or
             non-platinum regimens). Biologic therapies count as a prior line but hormonal
             therapies do not count.

          -  Platinum-resistant or platinum-sensitive recurrence.

          -  Must be able to take oral medications and have no evidence of bowel obstruction or
             partial bowel obstruction

          -  Measurable disease by either RECIST or Rustin criteria

          -  No chemotherapy, radiation therapy, nor biologic therapy within the last three weeks
             prior to initiating therapy

          -  ECOG score of 0 or 1

          -  Life expectancy of 12 weeks or greater

          -  18 years of age or older

          -  Laboratory values as outlined in the protocol

          -  Patients with treated limited stage basal cell or squamous cell carcinoma of the skin
             or carcinoma in situ of the breast or cervix are eligible. Subjects with stage I or II
             cancer treated with curative intent and no evidence of recurrent disease are also
             eligible.

          -  No evidence of preexisting hypertension. If patient has hypertension, it must be
             controlled medically (less than 150/90) prior to starting bevacizumab

          -  Normal blood coagulation parameters

          -  No prior treatment with any other antiangiogenic agents or cyclophosphamide

          -  For patients who have received prior doxorubicin or pegylated doxorubicin, LVEF must
             be 50% or greater.

        Exclusion Criteria:

          -  Current, recent (within 4 weeks of the first study infusion), or planned participation
             in an experimental drug study other than a Genentech-sponsored bevacizumab cancer
             study

          -  Active malignancy, other than superficial basal cell and superficial squamous (skin)
             cell, or carcinoma in situ of the cervix within last five years

          -  Uncontrolled diarrhea

          -  Prior history of hypertensive crisis or hypertensive encephalopathy

          -  NYHA Grade II or greater congestive heart failure

          -  History of myocardial infarction or unstable angina within 6 months prior to Day 1

          -  History of stroke or transient ischemic attack within 6 months prior to day 1

          -  Known CNS disease, except for treated brain metastasis

          -  Treated brain metastases are defined as having no evidence of progression or
             hemorrhage after treatment and no ongoing requirement for dexamethasone, as
             ascertained by clinical examination and brain imaging (MRI or CT) during the screening
             period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may
             include whole brain radiotherapy (WBRT), radiosurgery (RS: Gamma Knife, LINAC, or
             equivalent) or a combination as deemed appropriate by the treating physician. Patients
             with CNS metastases treated by neurosurgical resection or brain biopsy performed
             within 3 months prior to day 1 will be excluded.

          -  Significant vascular disease within 6 months prior to day 1

          -  History of hemoptysis within 1 month prior to day 1

          -  Evidence of bleeding diathesis or significant coagulopathy (in the absence of
             therapeutic anticoagulation)

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to day 1 or anticipation of need for major surgical procedure during the course
             of the study

          -  Core biopsy or other minor surgical procedure, excluding placement of a vascular
             access device, within 7 days prior to Day 1

          -  History of abdominal fistula or gastrointestinal perforation within 6 months prior to
             Day 1

          -  Serious, non-healing wound, active ulcer, or untreated bone fracture

          -  Proteinuria as demonstrated by a UPC ratio of 1.0 or greater at screening

          -  Known hypersensitivity to any component of bevacizumab

          -  Pregnancy (positive pregnancy test) or lactation. Use of effective means of
             contraception (men and women) in subjects of child-bearing potential