Trial of Pemetrexed and Bevacizumab for Recurrent Ovarian Primary Peritoneal Carcinoma

Inclusion Criteria

• Recurrent epithelial ovarian or primary peritoneal carcinoma. Histologic confirmation of the primary tumor is required. Patients with borderline tumors are not eligible.
• Patients must have measurable disease. Measurable disease is defined as at least one lesion that can be accurately measured in one dimension (longest dimension to be recorded). Each lesion must by > 20 mm when measured by conventional imaging techniques, including plain radiography, computed tomography and MRI or > 10 mm when measured by spiral CT.
• Patients must have at least one "target lesion" to assess response by RECIST criteria. Lesions within a previously irradiated field will be considered "non-target" lesions.
• Patients must have a GOG performance status of 0 or 1.
• Patients must have the ability to interrupt non-steroidal anti-inflammatory (NSAID) treatment 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of pemetrexed.
• Patients must have the ability to take folic acid, vitamin B12 and dexamethasone as described per protocol.
• Recovery from effects of recent surgery, radiotherapy or chemotherapy.
• Patients should be free of active infection requiring antibiotics.
• Any hormonal therapy directed at the tumor must be discontinued at least one week prior to registration. Continuation of hormone replacement therapy (HRT) is permitted.
• Any other prior therapy directed at the malignant tumor, including immunologic agents and cytotoxic 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 high-dose therapy, consolidation, or extended therapy administered after surgical or non-surgical assessment.
• Patients must have had one prior regimen containing a taxane compound. Patient may have received first-line treatment either intravenously or intraperitoneally.
• Patients must NOT have received prior therapy with pemetrexed or bevacizumab.
• Patients may have received a total of 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
• Any prior history of hypertensive crisis or hypertensive encephalopathy.
• Unstable angina within 6 months prior to study enrollment.
• New York Heart Association (NYHA) grade II or greater congestive heart failure.
• Serious cardiac arrhythmia requiring medication.
• Grade II or greater peripheral vascular disease. Patients with claudication within 6 months.
• History of myocardial infarction within 6 months.
• 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 the presence of ascites or other third space fluid which cannot be controlled by drainage.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 1 of study or anticipation of need for major surgical procedure during the course of the study.
• Patients with history or evidence upon physical examination of central nervous system disease, including primary brain tumor, brain metastases, seizure not controlled with standard medical therapy, history of cerebrovascular accident (CVA, stroke), or transient ischemic attack (TIA) or subarachnoid hemorrhage within 6 months of the first date of treatment on this study.
• Minor surgical procedures, other than central venous access placement, such as fine needle aspiration or core biopsy within 7 days prior to day 1 of study.
• Patients with proteinuria. At baseline patients will undergo a urine protein-creatinine ratio (UPCR) (Appendix IV). Patients with a UPCR > 1.0 at screening should be excluded. Urine dipstick for proteinuria may also be used. Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ pro