D2C7-IT via Convection-Enhanced Delivery in Treating Patients with Recurrent Malignant Glioma

Inclusion Criteria

• Patients must have a recurrent supratentorial WHO grade III or IV malignant glioma based on imaging studies
• Prior histopathology consistent with a supratentorial WHO grade III or IV malignant glioma
• Following biopsy, prior to administration of D2C7-IT, the presence of recurrent tumor must be confirmed by histopathological analysis
• Karnofsky performance status (KPS) >= 70%
• Platelet count >= 125,000 cells/mm^3 prior to biopsy; platelets >= 100,000 cells/mm^3 prior to infusion
• Hemoglobin >= 10 gm/dL prior to biopsy
• Absolute neutrophil count (ANC) >= 1500 cells/mm^3 prior to biopsy
• Serum creatinine =< 1.2 x the upper limit of normal (ULN) prior to biopsy
• Total bilirubin =< 1.6 mg/dL prior to biopsy
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x the ULN prior to biopsy
• Prothrombin (PT) and activated partial thromboplastin time (aPTT) =< 1.2 x upper limit of normal (ULN) prior to biopsy; patients with prior history of thrombosis/embolism are allowed to be on anticoagulation, understanding that anticoagulation will be held in the perioperative period per the neurosurgical team’s recommendations; low molecular weight heparin (LMWH) is preferred; if a patient is on warfarin, the international normalized ratio (INR) is to be obtained and value should be below 2.0 prior to biopsy
• Ability to comply with study and follow-up procedures
• If the patient is a sexually active female of child bearing potential, whose partner is male, or if the patient is a sexually active male, whose partner is a female of child bearing potential, the patient must agree to use appropriate contraceptive measures for the duration of the treatment of the tumor and for 6 months afterwards as stated in the informed consent; female patients of child bearing potential must have a negative serum pregnancy test at the time of screening and within 48 hours of starting the D2C7-IT infusion
• Patients will sign an Institutional Review Board (IRB)-approved informed consent form prior to any study-related procedures
• Able to undergo brain magnetic resonance imaging (MRI) with and without contrast
• RETREATMENT
• Subjects must satisfy the same inclusion and exclusion criteria for initial treatment as provided above
• Subjects must have benefited from initial treatment with D2C7-IT (i.e., be alive at least 12 months following their initial D2C7-IT infusion)
• Patients must not have experienced any serious adverse events (SAEs) or dose limiting toxicities (DLTs) related to the prior study drug infusion or study procedures (e.g., catheter implantation)
• Patients must have a recurrence of their supratentorial WHO grade III or IV malignant glioma based on imaging studies
• At the time of biopsy, prior to retreatment with D2C7-IT infusion, the presence of recurrent tumor must be confirmed by histopathological analysis, unless already proven within the last 3 months via tissue sampling (biopsy or resection)
• A new signed informed consent form for retreatment approved by the Duke University Institutional Review Board (IRB) will be required for retreatment; patients must be able to read and understand the informed consent document and must sign the informed consent indicating that they are aware of the investigational nature of this study

Exclusion Criteria

• Prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
• Pregnant or breastfeeding
• Patients with contrast-enhancing tumor component crossing the midline, actively growing multi-focal tumor, infratentorial tumor or extensive tumor dissemination (subependymal or leptomeningeal)
• Patients with clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatment
• Patients with a known severe allergy to gadolinium-DTPA; patients with mild allergies (e.g., rash only) will be pretreated with acetaminophen and diphenhydramine prior to injection of the contrast agent
• Unstable systemic disease in the opinion of the treating physician, for example active infection requiring intravenous (IV) antibiotics
• Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to admission for D2C7-IT infusion
• Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups)
• Patients who have not completed standard of care treatment prior to participation in this trial, i.e. surgical procedure and radiation therapy (at least 59 Gy); Note: If tumor is unmethylated, patients are not mandated to have received chemotherapy prior to participation in this trial; however, if tumor is methylated, patients must have received at least one chemotherapy regimen prior to participation in this trial
• Less than 12 weeks from radiation therapy, unless progressive disease outside of the radiation field or 2 progressive scans at least 4 weeks apart or histopathologic confirmation
• Treated with immunotherapeutic agents within 4 weeks before enrollment, unless the patient has recovered from the expected toxic effects of such therapy
• Treated with antiangiogenic agents (like bevacizumab) within 4 weeks before biopsy
• Treated with alkylating agents within 4 weeks before enrollment (6 weeks for nitrosoureas) or treated within 1 week before enrollment with daily or metronomic chemotherapy, unless the patient has recovered from the expected toxic effects of such therapy
• Prior chemotherapy (non-alkylating agents) within 2 weeks before enrollment, unless the patient has recovered from the expected toxic effects of such therapy