Know Cancer

forgot password

Phase I Trial and Pharmacokinetic Study of Temozolomide and O6-Benzylguanine in Childhood Solid Tumors

Phase 1
21 Years
Not Enrolling
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

Thank you

Trial Information

Phase I Trial and Pharmacokinetic Study of Temozolomide and O6-Benzylguanine in Childhood Solid Tumors


- 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

Inclusion Criteria


- 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

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Katherine Warren, MD

Investigator Role:

Study Chair

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

June 2000

Completion Date:

Related Keywords:

  • 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
  • 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
  • Carcinoma, Renal Cell
  • Kidney Neoplasms
  • Liver Neoplasms
  • Nervous System Neoplasms
  • Neuroblastoma
  • Ovarian Neoplasms
  • Central Nervous System Neoplasms
  • Neoplasms, Germ Cell and Embryonal
  • Neoplasms
  • Sarcoma



Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support Bethesda, Maryland  20892-1182