Sequential Angiogenic Blockade for the Treatment of Recurrent Mullerian Malignancies

• Status: Completed
• Trial end date: 2014-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Dana-Farber Cancer Institute
• Collaborators: Brigham and Women's Hospital; Genentech, Inc.; Massachusetts General Hospital
• Treatments: Bevacizumab; Cyclophosphamide

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