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.
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
- Conditions the study is for
- Brain and Central Nervous System Tumors, Childhood Germ Cell Tumor, Extragonadal Germ Cell Tumor
- 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
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.
- Conditions
- Brain and Central Nervous System Tumors, Childhood Germ Cell Tumor, Extragonadal Germ Cell Tumor, Kidney Cancer, Liver Cancer, Neuroblastoma
- 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.
O6-benzylguanineDrug
temozolomideDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startJun 2000
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Investigators
- Katherine Warren, MD, Study chair, National Cancer Institute (NCI)
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 19430790Warren 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
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial and Pharmacokinetic Study of Temozolomide and O6-Benzylguanine in Childhood Solid Tumors
- ClinicalTrials.gov ID
- NCT00020150
- Acronym / sponsor ID
- CDR0000067880
- Conditions
- Brain and Central Nervous System Tumors, Childhood Germ Cell Tumor, Extragonadal Germ Cell Tumor, Kidney Cancer, Liver Cancer, Neuroblastoma
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jun 2000
- First posted
- 27 Jan 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| O6-benzylguanine | Drug | – |
| temozolomide | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2015.
- Results publication: PubMed 19430790Meany 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.
- Results publication: PubMed 16234526Warren 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.
Related trials for Brain and Central Nervous System Tumors
RecruitingPhase 2
BrAin Metastasis in tripLe Negateive Breast Cancer: IvoneScimab and Trop2 ADC
Triple-Negative Breast Cancer (TNBC), Brain Metastases
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma
Recruiting
Virtual Home-based Exercise Intervention (RISE) to Improve Cancer-Related Cognitive Impairment and Gut Microbiome in Adolescent and Young Adult Brain Tumor Survivors
Cancer-related Cognitive Dysfunction, Primary Brain Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Katherine Warren, MD study chair
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
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.