a phase ii study of gliadel, concomitant temozolomide and radiation, followed by dose dense therapy with temozolomide plus bevacizumab for newly diagnosed malignant high grade glioma

Conditions: Glioma

Summary: to determine the safety and efficacy of surgical resection with gliadel® 3.85% wafer implantation, followed by concomitant limited field radiation therapy and temozolomide, followed by dose dense temozolomide and bevacizumab in subjects undergoing initial surgery for newly-diagnosed high grade glioma.


Eligibility criteria:
inclusion criteria: * subjects, men and women, must be between ages 18 and 75 years. * subjects must have radiographic evidence on cranial magnetic resonance imaging (mri) of a single, contrast-enhancing unilateral supratentorial cerebral tumor. * surgery is recommended within 4 weeks of the baseline mri scan. * subjects must have a karnofsky performance score of 60 or higher. * subjects must have signed an institutional review board (irb)-approved informed consent prior to any non-standard of care study procedure or no later than the start of dose dense temozolomide and bevacizumab.. * subjects must have a pathological diagnosis of a high grade (iv) malignant glioma. * subjects, both men and women, must be willing to avoid pregnancy for up to 2 years after wafer implantation surgery and be counseled regarding the unknown, and potentially harmful, risks to the embryo or fetus from participation in this study. exclusion criteria: * subjects who have had prior cytoreductive surgery for high-grade glioma. subjects who have had a diagnostic stereotactic biopsy are eligible. * subjects with more than one focus of tumor or tumor crossing the midline as assessed by coronal cranial mri scan. * concomitant significant life-threatening disease from which the subject could reasonably be expected to die within the first 12 months of the study. * known hypersensitivity reactions to temozolomide, nitrosoureas or any other components of the gliadel® wafer. * prior cns radiotherapy. * subjects who have received any prior chemotherapy for this malignant glioma prior to the baseline evaluation or subjects who are currently being treated with chemotherapeutic agents. * subjects with fewer than 100,000 platelets per mm3 or fewer than 3.500 leukocytes per mm3. * liver function tests greater than or equal to 2.5 times the upper limit of normal (transaminases (sgot, sgpt), total bilirubin, alkaline phosphatase). * serum creatinine equal to or greater than 1.5 times the upper limit of normal, blood urea nitrogen (bun) equal to or greater than 2.5 times the upper limit of normal. * pregnancy, or lactating females or females of childbearing potential not using adequate contraception. * participation in any other investigational protocol in the prior twelve months for any type of malignancy. * psychological, familial, sociological or geographical conditions which do not permit adequate medical follow-up and compliance with the study protocol. * inadequately controlled hypertension (blood pressure systolic \> 150 mmhg or diastolic \> 100 mmhg). * unstable angina or history of myocardial infarction within six months prior to enrollment. * evidence of bleeding, diathesis, or coagulopathy. chronic full-dose anticoagulation with warfarin is not permitted though subjects may be on low molecular weight heparin or fondaparinux. * serious non-healing wound, ulcer, or bone fracture.

Keywords: high grade malignant gbm