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Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors

This study has been completed.
Information provided by:
National Cancer Institute (NCI) Identifier:
First received: July 11, 2001
Last updated: April 28, 2015
Last verified: August 2004

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 combining temozolomide and O6-benzylguanine in treating children who have solid tumors that have not responded to previous therapy.

Condition Intervention Phase
Brain and Central Nervous System Tumors
Childhood Germ Cell Tumor
Extragonadal Germ Cell Tumor
Kidney Cancer
Liver Cancer
Ovarian Cancer
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: O6-benzylguanine
Drug: temozolomide
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase I Trial and Pharmacokinetic Study of Temozolomide and O6-Benzylguanine in Childhood Solid Tumors

Resource links provided by NLM:

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

Study Start Date: June 2000
Detailed Description:


  • Determine the maximum tolerated dose of temozolomide administered with a biologically active dose of O6-benzylguanine (O6-BG) in children with refractory solid tumors.
  • Determine the dose-limiting toxicity and the toxicity profile of this combination in these patients.
  • Assess the plasma pharmacokinetics of O6-BG and its active metabolite, 8-oxo-O6-BG, in these patients.
  • Assess the plasma pharmacokinetics of this combination in these patients.
  • Correlate levels of alanine-glyoxylate aminotransferase in peripheral blood mononuclear cells with the degree of hematologic toxicity of this combination in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive O6-benzylguanine (O6-BG) IV over 1 hour followed 30 minutes later by oral temozolomide daily for 5 days. Treatment continues every 28 days for up to 12 courses in the absence of unacceptable toxicity or disease progression.

Sequential dose escalation of O6-BG is followed by sequential dose escalation of temozolomide. Cohorts of 3-6 patients receive escalating doses of O6-BG and temozolomide until the maximum tolerated dose (MTD) of each is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 6 patients experience dose-limiting toxicity.

Quality of life is assessed at baseline and prior to courses 1, 3, 6, 8, and 12.

PROJECTED ACCRUAL: A total of 21-48 patients will be accrued for this study within 1-2 years.


Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed solid tumor refractory to standard therapy and for which no potentially curative therapy exists, including, but not limited to:

    • Rhabdomyosarcoma and other soft tissue sarcomas
    • Ewing's family of tumors
    • Osteosarcoma
    • Neuroblastoma
    • Wilms' tumor
    • Hepatic tumors
    • Germ cell tumors
    • Primary brain tumor
  • Histological confirmation may be waived for brainstem or optic gliomas
  • Measurable or evaluable disease
  • Evidence of progressive disease on prior chemotherapy or radiotherapy or persistent disease after prior surgery



  • 21 and under

Performance status:

  • ECOG 0-2

Life expectancy:

  • At least 8 weeks


  • Absolute granulocyte count greater than 1,500/mm^3
  • Hemoglobin greater than 8 g/dL
  • Platelet count greater than 100,000/mm^3


  • Bilirubin normal
  • SGPT less than 2 times upper limit of normal
  • No significant hepatic dysfunction


  • Creatinine normal OR
  • Creatinine clearance at least 60 mL/min


  • No significant cardiac dysfunction


  • No significant pulmonary dysfunction


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Able to swallow capsules
  • No significant unrelated systemic illness that would preclude study (e.g., serious infections or organ dysfunction)
  • No prior hypersensitivity to dacarbazine, temozolomide, or polyethylene glycol


Biologic therapy:

  • At least 1 week since prior colony-stimulating factors (e.g., filgrastim [G- CSF], sargramostim [GM-CSF], or epoetin alfa)
  • At least 4 months since prior myeloablative therapy requiring bone marrow or stem cell transplantation
  • No concurrent anticancer immunotherapy


  • See Disease Characteristics
  • At least 3 weeks since prior chemotherapy (4 weeks for nitrosoureas) and recovered
  • Prior temozolomide allowed provided not administered within past 3 months, no severe toxicities experienced during prior course, and not given in combination with other agents designed to inactivate alanine-glyoxylate aminotransferase
  • No other concurrent investigational or standard anticancer chemotherapy

Endocrine therapy:

  • Concurrent corticosteroids for control of brain tumor-associated edema allowed provided on stable or decreasing dose for at least 1 week prior to study


  • See Disease Characteristics
  • At least 4 weeks since prior limited-field radiotherapy
  • At least 4 months since prior craniospinal irradiation, total body irradiation, or radiotherapy to more than half of the pelvis
  • Recovered from prior radiotherapy
  • No concurrent anticancer radiotherapy


  • See Disease Characteristics


  • At least 4 weeks since other prior investigational therapy and recovered
  • No other concurrent anticancer 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 identifier: NCT00020150

United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
National Cancer Institute (NCI)
Study Chair: Katherine Warren, MD National Cancer Institute (NCI)
  More Information

Publications: Identifier: NCT00020150     History of Changes
Obsolete Identifiers: NCT00005019
Other Study ID Numbers: CDR0000067880
Study First Received: July 11, 2001
Last Updated: April 28, 2015

Keywords provided by National Cancer Institute (NCI):
recurrent childhood rhabdomyosarcoma
childhood craniopharyngioma
recurrent childhood brain tumor
recurrent neuroblastoma
recurrent childhood liver cancer
recurrent Wilms tumor and other childhood kidney tumors
childhood central nervous system germ cell tumor
recurrent osteosarcoma
unspecified childhood solid tumor, protocol specific
childhood germ cell tumor
recurrent childhood soft tissue sarcoma
childhood oligodendroglioma
childhood choroid plexus tumor
childhood grade I meningioma
childhood grade II meningioma
childhood grade III meningioma
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
recurrent childhood medulloblastoma
recurrent childhood visual pathway and hypothalamic glioma
previously treated childhood rhabdomyosarcoma
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
recurrent childhood ependymoma
childhood teratoma
childhood malignant testicular germ cell tumor
childhood extragonadal germ cell tumor
childhood malignant ovarian germ cell tumor
recurrent childhood malignant germ cell tumor

Additional relevant MeSH terms:
Liver Neoplasms
Neoplasms, Germ Cell and Embryonal
Kidney Neoplasms
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Nervous System Diseases
Antineoplastic Agents, Alkylating
Alkylating Agents processed this record on April 28, 2017