Brain and Central Nervous System TumorsPhase 1NCT00045721
Carmustine Implants and O(6)-Benzylguanine in Treating Children With Recurrent Malignant Glioma
A Phase 1 study testing O6-benzylguanine, polifeprosan 20 with carmustine implant and adjuvant therapy in people with Brain and Central Nervous System Tumors, run by Pediatric Brain Tumor Consortium at 9 sites 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. Chemotherapy placed into the surrounding tissue after surgery to remove the tumor may kill any remaining tumor cells. Read more about this study
- Who is it for?
- Ages 3 to 21 years
- Conditions the study is for
- Brain and Central Nervous System Tumors
- What is being tested?
- O6-benzylguanine, polifeprosan 20 with carmustine implant and adjuvant therapy
- Type of treatment
- Surgery or procedure
- How many people
- 3 participants
- Where
- 9 sitesUnited States
- Study dates
- Mar 2003to Jul 2004
- 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 3 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
DISEASE CHARACTERISTICS:
- Histologically confirmed progressive supratentorial anaplastic astrocytoma or glioblastoma multiforme
- No multifocal disease or leptomeningeal dissemination of tumor
- No evidence of tumor crossing midline
- Limited intraventricular involvement
- Measurable unilateral mass at least 10 mm by contrast-enhanced MRI
- Received prior involved-field radiotherapy as a component of prior therapy
- Amenable to and in need of significant debulking
PATIENT CHARACTERISTICS:
Age
- 3 to 21
Performance status
- Karnofsky 60-100% OR
- Lansky 60-100%
Life expectancy
- More than 8 weeks
Hematopoietic
- Absolute neutrophil count greater than 1,000/mm3*
- Platelet count greater than 100,000/mm3*
- Hemoglobin greater than 8 g/dL (transfusions allowed) NOTE: * Transfusion independent
Hepatic
- Bilirubin no greater than 1.5 times normal
- AST and ALT less than 3 times normal
- Albumin at least 2 g/dL
- No overt hepatic disease
Renal
- Creatinine clearance no greater than 1.5 times normal OR
- Glomerular filtration rate greater than 70 mL/min
- No overt renal disease
Cardiovascular
- No overt cardiac disease
Pulmonary
- No overt pulmonary disease
Other
- Neurological deficits must be stable for at least the past week
- No uncontrolled infection
- No known hypersensitivity to nitrosoureas or polyethylene glycol
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
- At least 6 months since prior bone marrow transplantation
- More than 2 weeks since prior colony-stimulating growth factors (e.g., filgrastim (G-CSF), sargramostim (GM-CSF), or epoetin alfa)
Chemotherapy
- No more than 2 prior cytotoxic chemotherapy regimens
- No more than 3 prior chemotherapy regimens total
- More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered
- Prior systemic carmustine (or other nitrosourea) allowed provided patient did not experience non-hematopoietic grade III/IV toxicity
Endocrine therapy
- Concurrent dexamethasone allowed if on a stable dose for at least the past week
Radiotherapy
- See Disease Characteristics
- At least 3 months since prior radiotherapy
- No prior craniospinal irradiation for metastatic disease
Surgery
- See Disease Characteristics
- Prior biopsy or cytoreductive surgery allowed
Other
- Concurrent anticonvulsants allowed
- No other concurrent anticancer or investigational drugs
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Duke Comprehensive Cancer Center
Durham, North Carolina, 27710
Texas Children's Cancer Center
Houston, Texas, 77030-2399
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105-2794
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104-4318
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15213
UCSF Comprehensive Cancer Center
San Francisco, California, 94143-0372
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, 98105
Children's National Medical Center
Washington D.C., District of Columbia, 20010-2970
About this study
Official title: Phase I Trial of GLIADEL and O(6)-Benzylguanine in Pediatric Patients With Recurrent Malignant Gliomas
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Chemotherapy placed into the surrounding tissue after surgery to remove the tumor may kill any remaining tumor cells. O(6)-benzylguanine may increase the effectiveness of carmustine by making tumor cells more sensitive to the drug.
PURPOSE: Phase I trial to study the safety of combining O(6)-benzylguanine with carmustine implants in treating children who have recurrent malignant glioma.
Read the detailed description
OBJECTIVES:
- Determine the dose of O(6)-benzylguanine that reliably inhibits alkylguanine-DNA alkyltransferase activity in pediatric patients with recurrent malignant glioma.
- Describe the toxic effects of O(6)-benzylguanine with carmustine implant (Gliadel) in these patients.
- Investigate antitumor response in patients treated with this regimen.
- Characterize the pharmacokinetics of O(6)-benzylguanine when administered continuously over a 9-day period.
OUTLINE: This is a multicenter, dose-escalation study of O(6)-benzylguanine.
Patients receive O(6)-benzylguanine (O6-BG) IV over 1 hour immediately followed by O6-BG IV continuously for 9 days. Two days after initiation of continuous infusion of O6-BG, patients undergo maximal tumor debulking. At the time of surgery, patients receive up to 8 polifeprosan 20 wafers with carmustine (Gliadel) implanted into the resection cavity.
Cohorts of up to 14 patients receive escalating doses of continuous infusion O6-BG until the optimally biologically effective dose (BED) is determined. The BED is defined as the dose at which at least 11 of 14 patients meet the target of complete suppression of alkylguanine-DNA alkyltransferase levels.
Patients are followed at day 11, at weeks 2, 4, 6, 8, and 12, at months 6, 9, and 12, every 6 months for 4 years, and then annually for 5 years.
PROJECTED ACCRUAL: Approximately 20 patients will be accrued for this study within 2 years.
- Conditions
- Brain and Central Nervous System Tumors
- Being tested
- O6-benzylguanine, polifeprosan 20 with carmustine implant, adjuvant therapy, conventional surgery, neoadjuvant therapy
- Keywords
- recurrent childhood cerebral astrocytoma
- Medical subject headings
- Central Nervous System Neoplasms, Astrocytoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
O6-benzylguanineDrug
polifeprosan 20 with carmustine implantDrug
adjuvant therapyProcedure or surgery
conventional surgeryProcedure or surgery
neoadjuvant therapyProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Biologically effective dose of O(6)-benzylguanine administered continuously in pediatric patients with recurrent malignant glioma
Toxicities associated with the administration of O(6)-benzylguanine and carmustine implants.
Secondary outcomes (1)
Tumor response
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 startMar 2003
- Primary completionJul 2004
- Study completionJul 2004
Why it stopped: Poor accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- 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
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pediatric Brain Tumor Consortium
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Investigators
- Ian F. Pollack, MD, Study chair, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00045721
- Sponsor's protocol ID
- CDR0000257268
- Other IDs
- PBTC-009
- Status last verified
- Oct 2009
- First submitted
- 6 Sep 2002
- Last updated
- 16 Oct 2009
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of GLIADEL and O(6)-Benzylguanine in Pediatric Patients With Recurrent Malignant Gliomas
- ClinicalTrials.gov ID
- NCT00045721
- Acronym / sponsor ID
- CDR0000257268
- Conditions
- Brain and Central Nervous System Tumors
- Keywords
- recurrent childhood cerebral astrocytoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor accrual
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Pediatric Brain Tumor ConsortiumResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Mar 2003
- Primary completion
- Jul 2004 (actual)
- Study completion
- Jul 2004 (actual)
- 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. Chemotherapy placed into the surrounding tissue after surgery to remove the tumor may kill any remaining tumor cells. O(6)-benzylguanine may increase the effectiveness of carmustine by making tumor cells more sensitive to the drug.
PURPOSE: Phase I trial to study the safety of combining O(6)-benzylguanine with carmustine implants in treating children who have recurrent malignant glioma.
Detailed description
OBJECTIVES:
- Determine the dose of O(6)-benzylguanine that reliably inhibits alkylguanine-DNA alkyltransferase activity in pediatric patients with recurrent malignant glioma.
- Describe the toxic effects of O(6)-benzylguanine with carmustine implant (Gliadel) in these patients.
- Investigate antitumor response in patients treated with this regimen.
- Characterize the pharmacokinetics of O(6)-benzylguanine when administered continuously over a 9-day period.
OUTLINE: This is a multicenter, dose-escalation study of O(6)-benzylguanine.
Patients receive O(6)-benzylguanine (O6-BG) IV over 1 hour immediately followed by O6-BG IV continuously for 9 days. Two days after initiation of continuous infusion of O6-BG, patients undergo maximal tumor debulking. At the time of surgery, patients receive up to 8 polifeprosan 20 wafers with carmustine (Gliadel) implanted into the resection cavity.
Cohorts of up to 14 patients receive escalating doses of continuous infusion O6-BG until the optimally biologically effective dose (BED) is determined. The BED is defined as the dose at which at least 11 of 14 patients meet the target of complete suppression of alkylguanine-DNA alkyltransferase levels.
Patients are followed at day 11, at weeks 2, 4, 6, 8, and 12, at months 6, 9, and 12, every 6 months for 4 years, and then annually for 5 years.
PROJECTED ACCRUAL: Approximately 20 patients will be accrued for this study within 2 years.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 3 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 | – |
| polifeprosan 20 with carmustine implant | Drug | – |
| adjuvant therapy | Procedure or surgery | – |
| conventional surgery | Procedure or surgery | – |
| neoadjuvant therapy | Procedure or surgery | – |
Primary outcome
Biologically effective dose of O(6)-benzylguanine administered continuously in pediatric patients with recurrent malignant glioma
Toxicities associated with the administration of O(6)-benzylguanine and carmustine implants.
1 secondary outcome
Tumor response
Results and safety
The study was stopped early (reason given: Poor accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2009.
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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.
Ian F. Pollack, MD study chair
University of Pittsburgh
9 sites 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, polifeprosan 20 with carmustine implant and adjuvant therapy in people with Brain and Central Nervous System Tumors, run by Pediatric Brain Tumor Consortium at 9 sites 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: stopped early, as of the sponsor's last update on 16 Oct 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites 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 was stopped early (reason given: Poor accrual). Results are not available in the source record.
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.
What does the primary outcome measure?
Biologically effective dose of O(6)-benzylguanine administered continuously in pediatric patients with recurrent malignant glioma. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Oct 2009.