Clinical trial NCT00393861: Study of Oxaliplatin Plus Bevacizumab in Germ Cell Tumor Patients
Official title: Phase II Study of Oxaliplatin Plus Bevacizumab Salvage Chemotherapy in Patients With Germ Cell Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neoplasms, Germ Cell and Embryonal
Keywords: Germ Cell Tumor
Germ Cell Cancer
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2006-10-29
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: 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.

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.

Primary outcomes:
measure: Twelve Month Disease-free Survival Rate
timeFrame: 12 month post completion of treatment
Secondary outcomes:
measure: Objective Response Rate (Complete and Partial Response)
timeFrame: completion of study, up to 5 years
measure: Duration of Remission (CR + PR)
timeFrame: completion of study, up to 5 years
measure: Overall Survival
timeFrame: completion of study, up to 5 years
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana Univeristy Cancer Center
state: Indiana
city: Philadelphia
country: United States
facility: University of Pennsylvania:Abramson Cancer Center
state: Pennsylvania
Study officials:
affiliation: Indiana Univeristy School of Medicine
name: Lawrence Einhorn, MD
role: PRINCIPAL_INVESTIGATOR
References: