O6-benzylguanine and Carmustine in Treating Children With Refractory CNS Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003765
First received: November 1, 1999
Last updated: February 4, 2013
Last verified: October 2007
  Purpose

Phase I trial to study the effectiveness of O6-benzylguanine and carmustine in treating children who have refractory CNS tumors. 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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: O6-benzylguanine
Drug: carmustine
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Trial of 06-BG and BCNU in Children With CNS Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Enrollment: 36
Study Start Date: May 1999
Primary Completion Date: March 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
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.
Drug: O6-benzylguanine Drug: carmustine

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  • 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
  • Bilirubin less than 1.5 mg/dL
  • SGOT/SGPT no greater than 2.5 times normal
  • Creatinine or GFR normal for age
  • If required, DLCO must be 80% of normal and patient old enough to cooperate for DLCO test
  • 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:

  • 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
  • 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
  • If receiving dexamethasone, must be on stable or decreasing dose for at least 2 weeks prior to study
  • 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
  • No other concurrent anticancer or investigational agents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003765

  Show 56 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Denise Adams, MD University of Vermont
  More Information

Additional Information:
Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003765     History of Changes
Other Study ID Numbers: NCI-2012-01842, POG-9870, CDR0000066891
Study First Received: November 1, 1999
Last Updated: February 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
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

Additional relevant MeSH terms:
Neoplasms
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Carmustine
O(6)-benzylguanine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 29, 2014