Study of Oxaliplatin Plus Bevacizumab in Germ Cell Tumor Patients

Inclusion Criteria

• Patients must have histological or serologic proof of metastatic germ cell neoplasm (gonadal or extragonadal primary). Patients with seminoma and non-seminoma are eligible, as are women with ovarian germ cell tumors.
• Patient's disease must not be amenable to cure with either surgery or chemotherapy in the opinion of the investigator.
• Patients must have failed initial cisplatin combination chemotherapy administered with curative intent such as BEP, EP, VIP, or similar regimens.
• Patients should have failed and demonstrated progressive disease with high dose chemotherapy such as carboplatin and etoposide. (With the exception of late relapse or primary mediastinal non-seminomatous germ cell tumor.
• Patients with late relapse or primary mediastinal non-seminomatous germ cell tumors must have failed at least 1 salvage chemotherapy regimen.
• Patients must have had prior exposure to paclitaxel, gemcitabine, or the combination of paclitaxel + gemcitabine.
• Patients must have adequate hematologic function (WBC > 4,000/mm3 and platelets > 100,000/mm3) obtained 1.5 are not eligible unless the patient is on anti-coagulants with a therapeutic INR between 1.5 and 3. Patients on coumadin are not eligible unless they are on low dose coumadin to keep a vascular access device patent.
• Patients with a history of arterial thromboses, unstable angina, transient ischemic attach (TIA), cerebral vascular accident (CVA), or a myocardial infarction within the last 6 months are not eligible.
• Patients must not have known CNS metastases. A Head CT or MRI will be performed only if clinically indicated.
• Patients must not have received any radiotherapy or chemotherapy within 28 days prior to study registration, and have recovered from all toxicity from prior treatments.
• Patients must not have any prior history of hypertensive crisis or hypertensive encephalopathy.
• Patients must not have New York Heart Association (NYHA) Grade II or greater congestive heart failure.
• Patients must not have history of significant vascular disease.
• Patients must not have evidence of bleeding diathesis or coagulopathy.
• Patients must not have inadequately controlled hypertension (defined as systolic blood pressure 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications).
• Patients must not have history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study registration.
• Patients must not have serious, non-healing would, ulcer or bone fracture.
• Patients must not have proteinuria at screening as demonstrated by a urine protein: Creatinine (UPC) ratio of ≥ 1.0.
• Patients must not have a known sensitivity to any component of bevacizumab.
• Patients must not be pregnant or lactating.
• Patients must not have grade 3 or 4 neuropathy.
• Females of child bearing potential must not be pregnant. A negative pregnancy test is required within 7 days prior to beginning treatment.

NOTE THE FOLLOWING GUIDELINES FOR USE IN THIS PROTOCOL:

• Progressive metastatic disease will be documented by the appearance of metastatic lesions on PA and lateral chest x-ray, C.T. scan, or other imaging studies, or the presence of a rising serum HCG or AFP.
• If a rising serum marker is the only evidence of progressive disease, at least 2 consecutive determinations must be done exhibiting serologic progression and alternative causes for increased serum levels of these substances must not be present [cross reaction with LH (tested if necessary by testosterone suppression of LH), ingestion of marijuana, hepatitis, etc.].
• Patients will be considered to have failed a prior regimen if they fail to obtain a complete response per RECIST as outlined in section 6.
• Patients with clinical situation of growing teratoma (normal or declining markers and radiographic or clinical progression) should be considered for surgery.