O6-Benzylguanine and Temozolomide in Treating Young Patients With Recurrent or Progressive Gliomas or Brain Stem Tumors
Condition: Brain and Central Nervous System Tumors
MeSH terms: Glioma; Nervous System Neoplasms; Central Nervous System Neoplasms; Recurrence
Intervention: O6-benzylguanine; temozolomide
Intervention description: Dosing is based on the body surface area (BSA) calculated at the beginning of each course of therapy. O6-Benzylguanine, 120 mg/m^2, will be administered as a one-hour intravenous (IV) infusion, daily for 5 days. Four consecutive weeks will constitute one course. Courses will be repeated every 4 weeks for up to 12 courses of therapy.; Dosing is based on the body surface area (BSA) calculated at the beginning of each course of therapy. Temozolomide, 75 mg/m^2 (rounded to the nearest 5 mg, the size of the smallest capsule) will be given orally, 30 minutes following the completion of each infusion of O6-Benzylguanine. Four consecutive weeks will constitute one course. Courses will be repeated every 4 weeks for up to 12 courses.
Intervention MeSH terms: Temozolomide; O(6)-benzylguanine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Maximum age: 21 Years
Healthy volunteers: No
Keywords: recurrent childhood brain stem glioma; recurrent childhood brain tumor

Summary:

      This phase II trial is studying how well giving O6-benzylguanine together with temozolomide
      works in treating young patients with recurrent or progressive gliomas or brain stem tumors.
      Drugs used in chemotherapy, such as O6-benzylguanine and temozolomide , work in different
      ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. O6-benzylguanine may help temozolomide work better by making tumor cells more
      sensitive to the drug. Giving more than one drug (combination chemotherapy) may kill more
      tumor cells.
    

Eligibility criteria:

        INCLUSION CRITERIA

          -  Tumor: Participants must have a high-grade glioma (including e.g. histologically
             confirmed anaplastic astrocytoma, glioblastoma multiforme, anaplastic
             oligodendroglioma, anaplastic ganglioma, gliosarcoma) or a brainstem tumor (histologic
             confirmation waived) with documentation of disease recurrence or progression after
             treatment with standard therapy. Participants must have bi-dimensionally measurable
             disease, defined as at least 1 lesion that can be measured in ≥ 2 dimensions

          -  Age: 21 years of age or less

          -  Performance status: Karnofsky 60-100% (for patients > 16 years of age) or Lansky
             60-100% (for patients ≤ 16 years of age)

          -  Life expectancy: Not specified

          -  Hematopoietic: Must have adequate bone marrow function defined as absolute neutrophil
             count > 1,500/mm^3, platelet count > 100,000/mm^3 (unsupported), hemoglobin > 8 g/dL
             (may be supported), and absolute lymphocyte count ≥ 500/mm^3

          -  Hepatic: Must have SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN), bilirubin ≤
             1.5 times ULN, and no overt hepatic disease

          -  Renal: Participants must have creatinine clearance ≥ 60 mL/min or creatinine based on
             age as follows: no greater than 0.8 mg/dL (for patients ≤ 5 years of age), no greater
             than 1.0 mg/dL (for patients 6 to 10 years of age), no greater than 1.2 mg/dL (for
             patients 11 to 15 years of age), or no greater than 1.5 mg/dL (for patients > 15 years
             of age). There must be no overt renal disease

          -  Cardiovascular: Must have no overt cardiac disease

          -  Pulmonary: Must have no overt pulmonary disease

          -  Other: Female participants of childbearing potential must have a negative pregnancy
             test prior to study registration, and must avoid breast-feeding. Female and male
             participants of childbearing or child-fathering potential must use effective
             contraception

          -  Bone Marrow Transplant: Must be at least 6 months since prior allogeneic bone marrow
             transplantation and at least 3 months since prior autologous bone marrow or stem cell
             transplantation

          -  Growth Factors: Must be at least 2 weeks since prior colony-stimulating factors (e.g.,
             filgrastim [G-CSF], sargramostim [GM-CSF], or erythropoietin)

          -  Prior Chemotherapy: Must have received last dose of myelosuppressive anticancer
             chemotherapy ≥ 3 weeks prior to study registration and ≥ 6 weeks for nitrosoureas.
             Must have received last dose of nonmyelosuppressive investigational agents or
             anticancer drugs ≥ 7 days prior to study registration. Participants who have received
             prior temozolomide are eligible

          -  Concurrent Endocrine Therapy: Concurrent corticosteroid therapy is allowed

          -  Prior Radiotherapy: Must have received last fraction of craniospinal irradiation and
             local irradiation to the primary tumor ≥ 12 weeks prior to study registration

          -  Prior Therapy-Other: Must have recovered from all prior therapy

        EXCLUSION CRITERIA

          -  Must not have history of severe toxicity (≥ grade 3) associated with temozolomide

          -  Must not be receiving other concurrent anticancer or investigational therapy

          -  Must not have history of hypersensitivity to dacarbazine, temozolomide, or
             polyethylene glycol (PEG)

          -  Must not have uncontrolled significant systemic illness including infection, or overt
             renal, hepatic, cardiac, or pulmonary disease

          -  Must not be HIV positive