Study of Oxaliplatin Plus Bevacizumab in Germ Cell Tumor Patients
Condition: Neoplasms, Germ Cell and Embryonal
MeSH terms: Neoplasms, Germ Cell and Embryonal
Intervention: Bevacizumab and Oxaliplatin
Intervention description: Oxaliplatin 85 mg/M2 IV over 2 hours plus Bevacizumab 10 mg/kg IV over 90 minutes
Intervention MeSH terms: Bevacizumab; Oxaliplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Germ Cell Tumor; Germ Cell Cancer

Summary:

      The purpose of this study is to evaluate the effectiveness of oxaliplatin and bevacizumab in
      patients with refractory or relapsed germ cell tumors.
    

Eligibility criteria:

        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 < 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.

        Exclusion Criteria:

          -  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
             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.