Phase II Study of Oxaliplatin Plus Bevacizumab Salvage Chemotherapy in Patients With Germ Cell Tumors
- 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 < 4 weeks prior to registration.
- Patients must have adequate hepatocellular function (SGOT < 4 x normal and Bilirubin
<2.0 mg/dl) obtained < 4 weeks from protocol registration.
- Serum Creatinine must be < 2.0 mg/dl obtained < 4 weeks from protocol registration.
- Patients must have an ECOG performance status of 0, 1, or 2.
- Patients must be at least 28 days post major surgery, open biopsy, or significant
traumatic injury at time of study registration.
- Patients must be at least 7 days post any minor surgical procedure, excluding
placement of a vascular access device at the time of study registration.
- Patients must be at least 18 years old at time of consent.
- Patients who have an active, unresolved infection and/or are receiving concurrent
treatment with parenteral antibiotics are ineligible. Patients are eligible after
antibiotics have been discontinued for at least 7 days.
- Patients may not have any significant bleeding.
- Patients with INR > 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
- 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
- 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.