Clinical trial NCT00650923 (phase 1, status: completed)
Conditions: adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult giant cell glioblastoma, adult glioblastoma, adult gliosarcoma, adult mixed glioma, recurrent adult brain tumor
ICD codes: C84.67, C84.77, C84.7A, C84.60, C84.70, C84.62, C84.66, C84.67, C84.77, C84.7A, C84.60, C84.70, C84.62, C84.66, G47.13, J01.41, K11.22, K12.0, N96, F33.8, G03.2
Drugs: ziv-aflibercept, temozolomide
SMILES: CSCC[C@H](N)C(O)=O
Eligibility criteria:

        Criteria:

          -  Creatinine < = 1.5 mg/dL or creatinine clearance = > 60 mL/min

          -  At least 28 days since prior major surgery or open biopsy

          -  INR < = 1.5

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Karnofsky performance status 60-100%

          -  SGOT and SGPT < 2 times upper limit of normal (ULN)

          -  Bilirubin < 2 times ULN

          -  Life expectancy = > 12 weeks

          -  WBC = > 3,000/μL

          -  ANC= > 1,500/mm³

          -  Platelet count = > 100,000/mm³

          -  Hemoglobin = > 10 g/dL (transfusion allowed)

          -  At least 21 days since prior radiotherapy (groups 2 and 3)

          -  No prior Gliadel® wafers

          -  No concurrent major surgery

          -  Fertile patients must use effective contraception prior to, during, and for at least 6
             months after completion of study treatment

          -  At least 28 days since prior significant traumatic injury No evidence of bleeding
             diathesis or coagulopathy

          -  No serious or nonhealing wound, ulcer, or bone fracture

          -  No history of other cancer (except nonmelanoma skin cancer or carcinoma in situ of the
             cervix), unless in complete remission and off of all therapy for that disease for a
             minimum of 3 years

          -  No history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess
             gastrointestinal bleeding or diverticulitis within the past 6 months

          -  No prior cranial radiotherapy (group 1 only)

          -  No prior aflibercept

          -  No prior treatment for brain tumors, except concurrent radiotherapy and temozolomide
             or 2 or fewer 28-day courses of adjuvant temozolomide (groups 2 and 3)

          -  No prior or concurrent cytotoxic drug therapy, non-cytotoxic drug therapy, or
             experimental drug therapy for brain tumors (group 1 only)

          -  No concurrent major surgery

          -  No known hypersensitivity to CHO cell products or other recombinant human antibodies

          -  No history of hypersensitivity to a recombinant protein whereby reaction occurs during
             or immediately after infusion

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biological composition to other study agents

          -  No uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection or psychiatric illness or social situation that would limit compliance with
             study requirements

          -  No clinically significant cardiovascular disease within the past 6 months, including
             any of the following:

        History of ischemic or hemorrhagic stroke

          -  Myocardial infarction, coronary artery bypass graft, or unstable angina

          -  New York Heart Association class III-IV congestive heart failure, serious cardiac
             arrhythmia requiring medication, or unstable angina pectoris

          -  Clinically significant peripheral vascular disease

          -  Pulmonary embolism, deep vein thrombosis, or other thromboembolic event

          -  No disease that will obscure toxicity or dangerously alter drug metabolism

          -  Recovered from all prior therapy

          -  More than 28 days since prior and no concurrent investigational agents

          -  More than 7 days since prior core biopsy

          -  At least 23 days since prior temozolomide (groups 2 and 3)

          -  No concurrent combination antiretroviral therapy for HIV-positive patients

          -  No concurrent full-dose anticoagulants (e.g., warfarin or low molecular-weight
             heparin)

          -  Prophylactic doses allowed

          -  No concurrent routine prophylactic use of filgrastim (G-CSF)

          -  No other concurrent anticancer therapy (including chemotherapy, radiotherapy, hormonal
             treatment, or immunotherapy)

          -  Concurrent enzyme-inducing antiepileptic drugs (EIAED) or non-EIAED allowed

          -  Urine protein:creatinine ratio < = 1 or 24-hour urine protein < = 500 mg

          -  No significant medical illnesses that in the investigator's opinion cannot be
             adequately controlled with appropriate therapy or would compromise the patient's
             ability to tolerate therapy