Brain and Central Nervous System TumorsPhase 1NCT00003765
O6-benzylguanine and Carmustine in Treating Children With Refractory CNS Tumors
A Phase 1 study testing O6-benzylguanine and carmustine in people with Brain and Central Nervous System Tumors, run by National Cancer Institute (NCI) at 56 sites in 3 countries.
Trial summary
Phase I trial to study the effectiveness of O6-benzylguanine and carmustine in treating children who have refractory CNS tumors. 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. 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
- What is being tested?
- O6-benzylguanine and carmustine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 56 sitesin 3 countries
- Study dates
- May 1999to Mar 2006
- 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 or cytologically proven CNS tumor that is refractory to conventional therapy or for which no effective therapy is known
- Histological requirement may be waived for brainstem and optic gliomas
- Stratum 2: No bone marrow involvement
PATIENT CHARACTERISTICS:
- Age: 21 and under
- Performance status: Karnofsky 50-100% OR Lansky 50-100%
- Life expectancy: At least 8 weeks
- Absolute neutrophil count at least 1500/mm3
- Platelet count at least 100,000/mm3 (stratum 2: at least 125,000/mm3)
- Hemoglobin at least 8 g/dL
- Bilirubin less than 1.5 mg/dL
- SGOT/SGPT no greater than 2.5 times normal
- Creatinine or GFR normal for age
- If required, DLCO must be 80% of normal and patient old enough to cooperate for DLCO test
- Neurologic deficits must be stable for at least 2 weeks prior to study
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 6 months after study
PRIOR CONCURRENT THERAPY:
- At least 7 days since prior biologic therapy or immunotherapy and recovered
- At least 6 months since prior bone marrow transplant (stratum 1 only)
- At least 7 days since prior growth factors
- No concurrent filgrastim (G-CSF) prophylaxis
- Stratum 2: No prior bone marrow transplantation
- At least 2 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea) and recovered
- Stratum 2: No greater than 2 prior chemotherapy regimens
- No prior nitrosourea therapy
- If receiving dexamethasone, must be on stable or decreasing dose for at least 2 weeks prior to study
- At least 2 weeks since prior local palliative radiotherapy (small port)
- At least 6 months since prior substantial bone marrow radiation, total body irradiation, hemipelvic radiotherapy, or total abdominal/pelvic/chest or mantle/Y ports radiotherapy
- Recovered from prior radiotherapy
- Stratum 2: No prior central axis radiation
- No other concurrent anticancer or investigational agents
Trial locations and contacts
56 sites in 3 countries.
56 sites in 3 countries
United States51 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109-0752
Graham Children's Health Center
Asheville, North Carolina, 28801
Emory University Hospital - Atlanta
Atlanta, Georgia, 30322
Johns Hopkins Oncology Center
Baltimore, Maryland, 21231
Boston Floating Hospital Infants and Children
Boston, Massachusetts, 02111
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Roswell Park Cancer Institute
Buffalo, New York, 14263-0001
Medical University of South Carolina
Charleston, South Carolina, 29425-0721
Robert H. Lurie Comprehensive Cancer Center, Northwestern University
Chicago, Illinois, 60611
Children's Memorial Hospital, Chicago
Chicago, Illinois, 60614
Children's Hospital Medical Center - Cincinnati
Cincinnati, Ohio, 45229-3039
Children's Hospital of Columbus
Columbus, Ohio, 43205-2696
Simmons Cancer Center - Dallas
Dallas, Texas, 75235-9154
Children's Hospital of Michigan
Detroit, Michigan, 48201
Duke Comprehensive Cancer Center
Durham, North Carolina, 27710
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, 76104
University of Florida Health Science Center
Gainesville, Florida, 32610-0296
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Texas Children's Cancer Center
Houston, Texas, 77030-2399
University of Texas - MD Anderson Cancer Center
Houston, Texas, 77030-4009
Indiana University Cancer Center
Indianapolis, Indiana, 46202-5265
University of Mississippi Medical Center
Jackson, Mississippi, 39216-4505
University of Kansas Medical Center
Kansas City, Kansas, 66160-7357
Children's Mercy Hospital
Kansas City, Missouri, 64108
University of California San Diego Cancer Center
La Jolla, California, 92093-0658
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Children's Hospital Los Angeles
Los Angeles, California, 90027-0700
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, 90095-1781
City of Hope National Medical Center
Los Angeles, California, 91010
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, 53792
Midwest Children's Cancer Center
Milwaukee, Wisconsin, 53226
University of Minnesota Cancer Center
Minneapolis, Minnesota, 55455
Vanderbilt Cancer Center
Nashville, Tennessee, 37232-6838
Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901
NYU School of Medicine's Kaplan Comprehensive Cancer Center
New York, New York, 10016
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
Columbia Presbyterian Hospital
New York, New York, 10032
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73190
Children's Hospital of Orange County
Orange, California, 92868
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905
Primary Children's Medical Center
Salt Lake City, Utah, 84113
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78284-7811
UCSF Cancer Center and Cancer Research Institute
San Francisco, California, 94115-0128
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, 98105
Cardinal Glennon Children's Hospital
St Louis, Missouri, 63104
Washington University School of Medicine
St Louis, Missouri, 63110
Stanford University Medical Center
Stanford, California, 94305-5408
State University of New York - Upstate Medical University
Syracuse, New York, 13210
Children's National Medical Center
Washington D.C., District of Columbia, 20010-2970
Canada3 sites
Montreal Children's Hospital
Montreal, Quebec, H3H 1P3
Hopital Sainte Justine
Montreal, Quebec, H3T 1C5
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
Australia2 sites
Royal Children's Hospital
Parkville, Victoria, 3052
Princess Margaret Hospital for Children
Perth, Western Australia, 6001
About this study
Official title: A Trial of 06-BG and BCNU in Children With CNS Tumors
Phase I trial to study the effectiveness of O6-benzylguanine and carmustine in treating children who have refractory CNS tumors. 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.
Read the detailed description
OBJECTIVES:
- Determine the maximum tolerated dose and the dose limiting toxicity of carmustine administered after O6-benzylguanine in children with refractory primary CNS tumors.
II. Determine a safe and tolerable dose of carmustine administered after O6-benzylguanine to be used in phase II studies.
III. Determine the pharmacokinetics of O6-benzylguanine and its metabolite, O6-benzyl-8-oxoguanine, in these patients.
IV. Seek preliminary evidence of antitumor activity of this regimen in these patients.
- Evaluate the acute and chronic toxicities, and describe cumulative toxicity, in patients treated with multiple courses of this regimen.
OUTLINE: This is a dose escalation study of carmustine.
Patients receive O6-benzylguanine IV over 1 hour, then, 1 hour later, carmustine IV is administered over 1 hour. Treatment is repeated every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients each receive escalating doses of carmustine until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose level at which fewer than 2 of 6 patients experience dose limiting toxicity (DLT). If myelosuppression is the DLT, stratum 1 is closed and patients are accrued to stratum 2. If neutropenia is the DLT in stratum 2, patients receive filgrastim (G-CSF) subcutaneously beginning on day 2 and continuing until blood counts recover. Patients are followed every 6 months for 4 years, then annually thereafter.
- Conditions
- Brain and Central Nervous System Tumors
- Being tested
- O6-benzylguanine, carmustine
- Keywords
- childhood craniopharyngioma, childhood central nervous system germ cell tumor, childhood oligodendroglioma, childhood choroid plexus tumor, recurrent childhood brain stem glioma, recurrent childhood supratentorial primitive neuroectodermal tumor, recurrent childhood visual pathway glioma, recurrent childhood cerebellar astrocytoma, recurrent childhood cerebral astrocytoma, recurrent childhood medulloblastoma, recurrent childhood ependymoma
- Medical subject headings
- Central Nervous System Neoplasms, Oligodendroglioma, Choroid Plexus Neoplasms, Optic Nerve Glioma, Astrocytoma, Medulloblastoma, Familial ependymoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
O6-benzylguanineDrug
carmustineDrug
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients receive O6-benzylguanine IV over 1 hour, then, 1 hour later, carmustine IV is administered over 1 hour. Treatment is repeated every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients each receive escalating doses of carmustine until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose level at which fewer than 2 of 6 patients experience dose limiting toxicity (DLT). If myelosuppression is the DLT, stratum 1 is closed and patients are accrued to stratum 2. If neutropenia is the DLT in stratum 2, patients receive filgrastim (G-CSF) subcutaneously beginning on day 2 and continuing until blood counts recover. Receives: Drug: O6-benzylguanine; Drug: carmustine |
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2004 (estimated)
- Study startMay 1999
- Primary completionMar 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Denise Adams, MD, Study chair, University of Vermont
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00003765
- Sponsor's protocol ID
- NCI-2012-01842
- Other IDs
- POG-9870, CDR0000066891
- Status last verified
- Oct 2007
- First submitted
- 1 Nov 1999
- Last updated
- 5 Feb 2013
- Results posted
- No
Publications
Adams DM, Zhou T, Berg SL, Bernstein M, Neville K, Blaney SM; Children's Oncology Group. Phase 1 trial of O6-benzylguanine and BCNU in children with CNS tumors: a Children's Oncology Group study. Pediatr Blood Cancer. 2008 Mar;50(3):549-53. doi: 10.1002/pbc.21362.
PubMed 17941066
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Trial of 06-BG and BCNU in Children With CNS Tumors
- ClinicalTrials.gov ID
- NCT00003765
- Acronym / sponsor ID
- NCI-2012-01842
- Conditions
- Brain and Central Nervous System Tumors
- Keywords
- childhood craniopharyngioma, childhood central nervous system germ cell tumor, childhood oligodendroglioma, childhood choroid plexus tumor, recurrent childhood brain stem glioma, recurrent childhood supratentorial primitive neuroectodermal tumor, recurrent childhood visual pathway glioma, recurrent childhood cerebellar astrocytoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- May 1999
- Primary completion
- Mar 2006 (actual)
- First posted
- 27 Apr 2004 (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.
Phase I trial to study the effectiveness of O6-benzylguanine and carmustine in treating children who have refractory CNS tumors. 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.
Detailed description
OBJECTIVES:
- Determine the maximum tolerated dose and the dose limiting toxicity of carmustine administered after O6-benzylguanine in children with refractory primary CNS tumors.
II. Determine a safe and tolerable dose of carmustine administered after O6-benzylguanine to be used in phase II studies.
III. Determine the pharmacokinetics of O6-benzylguanine and its metabolite, O6-benzyl-8-oxoguanine, in these patients.
IV. Seek preliminary evidence of antitumor activity of this regimen in these patients.
- Evaluate the acute and chronic toxicities, and describe cumulative toxicity, in patients treated with multiple courses of this regimen.
OUTLINE: This is a dose escalation study of carmustine.
Patients receive O6-benzylguanine IV over 1 hour, then, 1 hour later, carmustine IV is administered over 1 hour. Treatment is repeated every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients each receive escalating doses of carmustine until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose level at which fewer than 2 of 6 patients experience dose limiting toxicity (DLT). If myelosuppression is the DLT, stratum 1 is closed and patients are accrued to stratum 2. If neutropenia is the DLT in stratum 2, patients receive filgrastim (G-CSF) subcutaneously beginning on day 2 and continuing until blood counts recover. Patients are followed every 6 months for 4 years, then annually thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: O6-benzylguanine, Drug: carmustinePatients receive O6-benzylguanine IV over 1 hour, then, 1 hour later, carmustine IV is administered over 1 hour. Treatment is repeated every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients each receive escalating doses of carmustine until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose level at which fewer than 2 of 6 patients experience dose limiting toxicity (DLT). If myelosuppression is the DLT, stratum 1 is closed and patients are accrued to stratum 2. If neutropenia is the DLT in stratum 2, patients receive filgrastim (G-CSF) subcutaneously beginning on day 2 and continuing until blood counts recover. |
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 | Arm I |
| carmustine | Drug | Arm I |
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 5 Feb 2013.
- Results publication: PubMed 17941066Adams DM, Zhou T, Berg SL, Bernstein M, Neville K, Blaney SM; Children's Oncology Group. Phase 1 trial of O6-benzylguanine and BCNU in children with CNS tumors: a Children's Oncology Group study. Pediatr Blood Cancer. 2008 Mar;50(3):549-53. doi: 10.1002/pbc.21362.
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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.
Denise Adams, MD study chair
University of Vermont
56 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing O6-benzylguanine and carmustine in people with Brain and Central Nervous System Tumors, run by National Cancer Institute (NCI) at 56 sites in 3 countries.
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 5 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 56 sites in United States, Canada, Australia. 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 NCT00003765, which also lists 1 linked publication.
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 5 Feb 2013.