Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00020150
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : April 29, 2015
Information provided by:
National Cancer Institute (NCI)

July 11, 2001
January 27, 2003
April 29, 2015
June 2000
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Complete list of historical versions of study NCT00020150 on Archive Site
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Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors
Phase I Trial and Pharmacokinetic Study of Temozolomide and O6-Benzylguanine in Childhood Solid Tumors

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.


  • 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.

Phase 1
Primary Purpose: Treatment
  • Brain and Central Nervous System Tumors
  • Childhood Germ Cell Tumor
  • Extragonadal Germ Cell Tumor
  • Kidney Cancer
  • Liver Cancer
  • Neuroblastoma
  • Ovarian Cancer
  • Sarcoma
  • Unspecified Childhood Solid Tumor, Protocol Specific
  • Drug: O6-benzylguanine
  • Drug: temozolomide
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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  • 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
Sexes Eligible for Study: All
up to 21 Years   (Child, Adult)
Contact information is only displayed when the study is recruiting subjects
United States
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National Cancer Institute (NCI)
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Study Chair: Katherine Warren, MD National Cancer Institute (NCI)
National Cancer Institute (NCI)
August 2004

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP