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| Sponsors and Collaborators: |
Pediatric Oncology Group National Cancer Institute (NCI) |
|---|---|
| Information provided by: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00003765 |
Purpose
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of O6-benzylguanine and carmustine in treating children who have refractory CNS tumors.
| Condition | Intervention | Phase |
|---|---|---|
|
Brain and Central Nervous System Tumors |
Drug: O6-benzylguanine Drug: carmustine |
Phase I |
| Study Type: | Interventional |
| Study Design: | Treatment |
| Official Title: | A Trial of 06-BG and BCNU in Children With CNS Tumors |
| Estimated Enrollment: | 36 |
| Study Start Date: | May 1999 |
OBJECTIVES: I. Determine the maximum tolerated dose and the dose limiting toxicity of carmustine administered after O6-benzylguanine in children with refractory primary CNS tumors. II. Determine a safe and tolerable dose of carmustine administered after O6-benzylguanine to be used in phase II studies. III. Determine the pharmacokinetics of O6-benzylguanine and its metabolite, O6-benzyl-8-oxoguanine, in these patients. IV. Seek preliminary evidence of antitumor activity of this regimen in these patients. V. Evaluate the acute and chronic toxicities, and describe cumulative toxicity, in patients treated with multiple courses of this regimen.
OUTLINE: This is a dose escalation study of carmustine. Patients receive O6-benzylguanine IV over 1 hour, then, 1 hour later, carmustine IV is administered over 1 hour. Treatment is repeated every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients each receive escalating doses of carmustine until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose level at which fewer than 2 of 6 patients experience dose limiting toxicity (DLT). If myelosuppression is the DLT, stratum
1 is closed and patients are accrued to stratum 2. If neutropenia is the DLT in stratum 2, patients receive filgrastim (G-CSF) subcutaneously beginning on day 2 and continuing until blood counts recover. Patients are followed every 6 months for 4 years, then annually thereafter.
PROJECTED ACCRUAL: Approximately 3-36 patients will be accrued for this study within 3 years.
Eligibility| Ages Eligible for Study: | up to 21 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS: Histologically or cytologically proven CNS tumor that is refractory to conventional therapy or for which no effective therapy is known Histological requirement may be waived for brainstem and optic gliomas Stratum 2: No bone marrow involvement
PATIENT CHARACTERISTICS: Age: 21 and under Performance status: Karnofsky 50-100% OR Lansky 50-100% Life expectancy: At least 8 weeks Hematopoietic: Absolute neutrophil count at least 1500/mm3 Platelet count at least 100,000/mm3 (stratum 2: at least 125,000/mm3) Hemoglobin at least 8 g/dL Hepatic: Bilirubin less than 1.5 mg/dL SGOT/SGPT no greater than 2.5 times normal Renal: Creatinine or GFR normal for age Pulmonary: If required, DLCO must be 80% of normal and patient old enough to cooperate for DLCO test Other: Neurologic deficits must be stable for at least 2 weeks prior to study Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 6 months after study
PRIOR CONCURRENT THERAPY: Biologic therapy: At least 7 days since prior biologic therapy or immunotherapy and recovered At least 6 months since prior bone marrow transplant (stratum 1 only) At least 7 days since prior growth factors No concurrent filgrastim (G-CSF) prophylaxis Stratum 2: No prior bone marrow transplantation Chemotherapy: At least 2 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea) and recovered Stratum 2: No greater than 2 prior chemotherapy regimens No prior nitrosourea therapy Endocrine therapy: If receiving dexamethasone, must be on stable or decreasing dose for at least 2 weeks prior to study Radiotherapy: At least 2 weeks since prior local palliative radiotherapy (small port) At least 6 months since prior substantial bone marrow radiation, total body irradiation, hemipelvic radiotherapy, or total abdominal/pelvic/chest or mantle/Y ports radiotherapy Recovered from prior radiotherapy Stratum 2: No prior central axis radiation Surgery: Not specified Other: No other concurrent anticancer or investigational agents
Contacts and Locations
Show 56 Study Locations| Study Chair: | Denise Adams, MD | University of Vermont |
More Information
| Study ID Numbers: | CDR0000066891, POG-9870 |
| Study First Received: | November 1, 1999 |
| Last Updated: | July 23, 2008 |
| ClinicalTrials.gov Identifier: | NCT00003765 History of Changes |
| Health Authority: | United States: Federal Government |
|
childhood craniopharyngioma childhood central nervous system germ cell tumor childhood oligodendroglioma childhood choroid plexus tumor recurrent childhood brain stem glioma recurrent childhood supratentorial primitive neuroectodermal tumor |
recurrent childhood visual pathway glioma recurrent childhood cerebellar astrocytoma recurrent childhood cerebral astrocytoma recurrent childhood medulloblastoma recurrent childhood ependymoma |
|
Choroid Plexus Neoplasms Neuroectodermal Tumors, Primitive Astrocytoma Carmustine Central Nervous System Neoplasms Ependymoma Recurrence Neuroectodermal Tumors Brain Stem Glioma, Childhood |
Medulloblastoma Craniopharyngioma Neuroepithelioma O(6)-benzylguanine Oligodendroglioma Antineoplastic Agents, Alkylating Glioma Alkylating Agents Nervous System Neoplasms |
|
Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Nervous System Diseases Carmustine Enzyme Inhibitors Central Nervous System Neoplasms Pharmacologic Actions |
Neoplasms Neoplasms by Site Therapeutic Uses O(6)-benzylguanine Antineoplastic Agents, Alkylating Alkylating Agents Nervous System Neoplasms |
