Medpedia

• Neoplasms, Germ Cell and Embryonal

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.

This study proposes to look at the established combination of oxaliplatin and bevacizumab as
used in colorectal cancer in refractory germ cell tumor patients.  Oxaliplatin is a drug of
known activity.  Although bevacizumab has no single agent data, it combines dramatically
well with numerous chemotherapy drugs, such as oxaliplatin increasing response rates and
improving survival.  Furthermore, VEG-F appears to be an important target in germ cell
tumors as it does in so many other types of solid tumors.  We will be using the identical
dosages of oxaliplatin + bevacizumab as has been utilized in previously treated colorectal
cancer, without the addition of 5-FU + leucovorin.  This dose and schedule has been proven
to be safe and effective.

• Drug: Bevacizumab and Oxaliplatin
  Oxaliplatin 85 mg/M2 IV over 2 hours plus Bevacizumab 10 mg/kg IV over 90 minutes

• The primary objective is to determine the 12 month continuous disease-free survival rate of oxaliplatin and bevacizumab in refractory germ cell tumors.
  12 month post completion of treatment
  Safety Issue: No
• The secondary objective is to determine the partial and complete response rates and duration of remission
  completion of study
  Safety Issue: No

• Lawrence Einhorn, MD
  Principal Investigator, Indiana Univeristy School of Medicine

• University of Pennsylvania:Abramson Cancer Center
  Philadelphia, Pennsylvania, 19104, United States
  Recruiting
  Janelle Robinson

  (215) 662-7398

  Janelle.Robinson@uphs.upenn.edu

  Investigators

  • David Vaughn, MD
    Principal Investigator
• Indiana Univeristy Cancer Center
  Indianapolis, Indiana, 46202, United States
  Recruiting
  Jackie Brames, RN

  (317) 274-7929

  mjbrames@iupui.edu

  Investigators

  • Lawrence Einhorn, MD
    Principal Investigator

• Indiana University School of Medicine
  Lead Sponsor
• United States: Institutional Review Board

• Indiana University Cancer Center Clinical Trials website
  http://cancer.iu.edu/sip/SIPControlServlet