A Phase II Randomized Trial Comparing the Efficacy of Heat Shock Protein-Peptide Complex-96 (HSPPC-96) (NSC #725085, ALLIANCE IND # 15380) Vaccine Given With Bevacizumab Versus Bevacizumab Alone in the Treatment of Surgically Resectable Recurrent Glioblastoma Multiforme (GBM)

Date de début de l'étude : 19 juin 2013

Pre-registration (Pre-Surgery) Eligibility Criteria Histologic documentation: Prior histologic diagnosis of GBM at first occurrence Stage: First or second recurrence of GBM or gliosarcoma considered to be surgically resectable Prior Treatment: No radiotherapy within 90 days prior to pre-registration No prior treatment with any anti-angiogenic agent targeting the VEGF pathway including but not limited to bevacizumab, cediranib, vandetanib, sunitinib, pazopanib, aflibercept, or sorafenib No prior treatment with HSPPC-96 or other investigational immunotherapy Must have received prior treatment with radiotherapy and temozolomide for histologically confirmed GBM at initial diagnosis No tumor directed therapy for most recent progression No prior Gliadel® wafers No clinically significant cardiovascular disease: Patients with a history of hypertension must be well controlled (<150/90) on a regimen of antihypertensive therapy. History of arterial thrombotic events within the past 6 months, including transient ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus, unstable angina or angina requiring surgical or medial intervention in the past 6 months, or myocardial infarction (MI). Patients with clinically significant peripheral artery disease (i.e., claudication on less than one block), significant vascular disease (i.e., aortic aneurysm, history of aortic dissection) are not eligible. Patients who have had a deep vein thrombosis or pulmonary embolus within the past 6 months are eligible if they are on stable therapeutic anticoagulation No current New York Heart Association classification II, III or IV congestive heart failure No significant bleeding within the past 6 months; no bleeding diathesis or coagulopathy No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within past 12 months No evidence of any systemic autoimmune disease (e.g. Hashimoto's thyroiditis) and/or any history of primary or secondary immunodeficiency, and no immunosuppressant therapy (with the exception of dexamethasone as noted below) for any reason Age ≥ 18 years of age Karnofsky functional status rating ≥70 No more than 16 mg dexamethasone (or equivalent) per day Non-pregnant and non-nursing Registration (Post-Surgery) Eligibility Criteria Pre-registration eligibility criteria continue to be met Histologic documentation: confirmed histological diagnosis of recurrent GBM or gliosarcoma ≥ 90% surgical resection of recurrent GBM confirmed by central radiology review by MRI with or without gadolinium per institutional guidelines. A CT scan is allowable in place of MRI only in situations where an MRI is contraindicated (e.g., patient has a heart pacemaker, metallic devices in the eye, brain or spine, severe claustrophobia). ≥ 7 grams of resected tumor available for vaccine manufacture as determined by institutional pathologist Availability of ≥ 6 clinical vials of HSPPC-96 Required Initial Laboratory Values: Granulocytes ≥1,500/µL Platelet count ≥100,000/µL Total Bilirubin ≤ 2.0 x ULN UPC ratio <1 or Urine protein ≤ 1+ Calculated creatinine clearance ≥ 45 ml/min SGOT/SGPT(AST/ALT) ≤ 2.5 x ULN No serious, non-healing wounds or ulcers At least 7 days since any minor surgery such as port placement No major surgical procedures, open biopsy or significant traumatic injury ≤ 28 days prior to registration or anticipation of need for elective or planned major surgical procedure during the study. Core biopsy or other minor surgical procedures ≤7 days prior to registration. No active or recent hemoptysis (≥½ teaspoon of bright red blood per episode) ≤ 30 days prior to registration No new bleeding on D28 (+/-3) MRI (or CT if MRI is contraindicated) No clinical deterioration at the time of registration/randomization If a second surgery is needed for completion of resection, this should be within 30 days from the first surgery