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Brain and Central Nervous System TumorsPhase 1NCT00020150

Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors

A Phase 1 study testing O6-benzylguanine and temozolomide in people with Brain and Central Nervous System Tumors and Childhood Germ Cell Tumor, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages Up to 21 years
What is being tested?
O6-benzylguanine and temozolomide
How many people
Not given
Where
1 siteUnited States
Study dates
Jun 2000to not given
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age:

  • 21 and under

Performance status:

  • ECOG 0-2

Life expectancy:

  • At least 8 weeks

Hematopoietic:

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

Hepatic:

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

Renal:

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

Cardiovascular:

  • No significant cardiac dysfunction

Pulmonary:

  • No significant pulmonary dysfunction

Other:

  • 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

PRIOR CONCURRENT THERAPY:

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

Chemotherapy:

  • 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

Radiotherapy:

  • 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

Surgery:

  • See Disease Characteristics

Other:

  • At least 4 weeks since other prior investigational therapy and recovered
  • No other concurrent anticancer investigational agents

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

    Bethesda, Maryland, 20892-1182

Other trials in United States

About this study

Official title: 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.

Read the detailed description

OBJECTIVES:

  • 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.

Being tested
O6-benzylguanine, temozolomide
Keywords
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
Medical subject headings
Central Nervous System Neoplasms, Kidney Neoplasms, Liver Neoplasms, Neuroblastoma, Ovarian Neoplasms, Sarcoma, Wilms Tumor, Osteosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startJun 2000

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
IDs, dates and publications
ClinicalTrials.gov ID
NCT00020150
Sponsor's protocol ID
CDR0000067880
Other IDs
NCI-00-C-0105I, NCI-237
Status last verified
Aug 2004
First submitted
11 Jul 2001
Last updated
29 Apr 2015
Results posted
No

Publications

  • Meany HJ, Warren KE, Fox E, Cole DE, Aikin AA, Balis FM. Pharmacokinetics of temozolomide administered in combination with O6-benzylguanine in children and adolescents with refractory solid tumors. Cancer Chemother Pharmacol. 2009 Dec;65(1):137-42. doi: 10.1007/s00280-009-1015-8. Epub 2009 May 9.

    PubMed 19430790
  • Warren KE, Aikin AA, Libucha M, Widemann BC, Fox E, Packer RJ, Balis FM. Phase I study of O6-benzylguanine and temozolomide administered daily for 5 days to pediatric patients with solid tumors. J Clin Oncol. 2005 Oct 20;23(30):7646-53. doi: 10.1200/JCO.2005.02.0024.

    PubMed 16234526

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing O6-benzylguanine and temozolomide in people with Brain and Central Nervous System Tumors and Childhood Germ Cell Tumor, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00020150, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2015.

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