Phase I Trial of GLIADEL and O(6)-Benzylguanine in Pediatric Patients With Recurrent Malignant Gliomas
Carmustine Implants and O(6)-Benzylguanine in Treating Children With Recurrent Malignant Glioma
Sponsors
Source
Pediatric Brain Tumor Consortium
Oversight Info
Has Dmc
Yes
Brief 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. 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.
Overall Status
Terminated
Start Date
2003-03-01
Completion Date
2004-07-01
Primary Completion Date
2004-07-01
Phase
Phase 1
Study Type
Interventional
Primary Outcome
Measure |
|
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 Outcome
Measure |
|
Tumor response |
Enrollment
3
Condition
Intervention
Eligibility
Criteria
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
Gender
All
Minimum Age
3 Years
Maximum Age
21 Years
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
|
Ian F. Pollack, MD |
Study Chair |
University of Pittsburgh |
Location
Facility |
|
UCSF Comprehensive Cancer Center San Francisco California 94143-0372 United States |
|
Children's National Medical Center Washington District of Columbia 20010-2970 United States |
|
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Boston Massachusetts 02115 United States |
|
Duke Comprehensive Cancer Center Durham North Carolina 27710 United States |
|
Children's Hospital of Philadelphia Philadelphia Pennsylvania 19104-4318 United States |
|
Children's Hospital of Pittsburgh Pittsburgh Pennsylvania 15213 United States |
|
St. Jude Children's Research Hospital Memphis Tennessee 38105-2794 United States |
|
Texas Children's Cancer Center Houston Texas 77030-2399 United States |
|
Children's Hospital and Regional Medical Center - Seattle Seattle Washington 98105 United States |
Location Countries
Country
United States
Verification Date
2009-10-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Name Title
James M. Boyett/PBTC Operations and Biostatistics Center Executive Director
Organization
Pediatric Brain Tumor Consortium
Keyword
Has Expanded Access
No
Condition Browse
Secondary Id
PBTC-009
Intervention Browse
Mesh Term
Carmustine
O(6)-benzylguanine
Firstreceived Results Date
N/A
Why Stopped
Poor accrual
Firstreceived Results Disposition Date
N/A
Study Design Info
Primary Purpose
Treatment
Study First Submitted
September 6, 2002
Study First Submitted Qc
January 26, 2003
Study First Posted
January 27, 2003
Last Update Submitted
October 15, 2009
Last Update Submitted Qc
October 15, 2009
Last Update Posted
October 16, 2009
ClinicalTrials.gov processed this data on December 12, 2019
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.