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O6-benzylguanine and Carmustine in Treating Children With Refractory CNS Tumors

Primary Purpose

Brain and Central Nervous System Tumors

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
O6-benzylguanine
carmustine
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring 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

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Arkansas for Medical Sciences
  • University of California San Diego Cancer Center
  • Children's Hospital Los Angeles
  • Jonsson Comprehensive Cancer Center, UCLA
  • City of Hope National Medical Center
  • Children's Hospital of Orange County
  • UCSF Cancer Center and Cancer Research Institute
  • Stanford University Medical Center
  • Children's National Medical Center
  • University of Florida Health Science Center
  • Emory University Hospital - Atlanta
  • Robert H. Lurie Comprehensive Cancer Center, Northwestern University
  • Children's Memorial Hospital, Chicago
  • Indiana University Cancer Center
  • University of Kansas Medical Center
  • Johns Hopkins Oncology Center
  • Boston Floating Hospital Infants and Children
  • Dana-Farber Cancer Institute
  • University of Michigan Comprehensive Cancer Center
  • Children's Hospital of Michigan
  • University of Minnesota Cancer Center
  • Mayo Clinic Cancer Center
  • University of Mississippi Medical Center
  • Children's Mercy Hospital
  • Cardinal Glennon Children's Hospital
  • Washington University School of Medicine
  • Hackensack University Medical Center
  • Cancer Institute of New Jersey
  • Roswell Park Cancer Institute
  • NYU School of Medicine's Kaplan Comprehensive Cancer Center
  • Memorial Sloan-Kettering Cancer Center
  • Columbia Presbyterian Hospital
  • State University of New York - Upstate Medical University
  • Graham Children's Health Center
  • Duke Comprehensive Cancer Center
  • Children's Hospital Medical Center - Cincinnati
  • Children's Hospital of Columbus
  • University of Oklahoma Health Sciences Center
  • Children's Hospital of Philadelphia
  • Children's Hospital of Pittsburgh
  • Medical University of South Carolina
  • Vanderbilt Cancer Center
  • Simmons Cancer Center - Dallas
  • Cook Children's Medical Center - Fort Worth
  • Texas Children's Cancer Center
  • University of Texas - MD Anderson Cancer Center
  • University of Texas Health Science Center at San Antonio
  • Primary Children's Medical Center
  • Children's Hospital and Regional Medical Center - Seattle
  • University of Wisconsin Comprehensive Cancer Center
  • Midwest Children's Cancer Center
  • Royal Children's Hospital
  • Princess Margaret Hospital for Children
  • Hospital for Sick Children
  • Montreal Children's Hospital
  • Hopital Sainte Justine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm I

Arm Description

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.

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
February 4, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00003765
Brief Title
O6-benzylguanine and Carmustine in Treating Children With Refractory CNS Tumors
Official Title
A Trial of 06-BG and BCNU in Children With CNS Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
October 2007
Overall Recruitment Status
Completed
Study Start Date
May 1999 (undefined)
Primary Completion Date
March 2006 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief 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.
Detailed Description
OBJECTIVES: I. 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. V. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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, recurrent childhood cerebral astrocytoma, recurrent childhood medulloblastoma, recurrent childhood ependymoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
O6-benzylguanine
Intervention Type
Drug
Intervention Name(s)
carmustine

10. Eligibility

Sex
All
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Denise Adams, MD
Organizational Affiliation
University of Vermont
Official's Role
Study Chair
Facility Information:
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
University of California San Diego Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093-0658
Country
United States
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027-0700
Country
United States
Facility Name
Jonsson Comprehensive Cancer Center, UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1781
Country
United States
Facility Name
City of Hope National Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Children's Hospital of Orange County
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
UCSF Cancer Center and Cancer Research Institute
City
San Francisco
State/Province
California
ZIP/Postal Code
94115-0128
Country
United States
Facility Name
Stanford University Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305-5408
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010-2970
Country
United States
Facility Name
University of Florida Health Science Center
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610-0296
Country
United States
Facility Name
Emory University Hospital - Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Robert H. Lurie Comprehensive Cancer Center, Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Children's Memorial Hospital, Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60614
Country
United States
Facility Name
Indiana University Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202-5265
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160-7357
Country
United States
Facility Name
Johns Hopkins Oncology Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Boston Floating Hospital Infants and Children
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-0752
Country
United States
Facility Name
Children's Hospital of Michigan
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
University of Minnesota Cancer Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Mayo Clinic Cancer Center
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216-4505
Country
United States
Facility Name
Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Cardinal Glennon Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Cancer Institute of New Jersey
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263-0001
Country
United States
Facility Name
NYU School of Medicine's Kaplan Comprehensive Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Columbia Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
State University of New York - Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Graham Children's Health Center
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28801
Country
United States
Facility Name
Duke Comprehensive Cancer Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Children's Hospital Medical Center - Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229-3039
Country
United States
Facility Name
Children's Hospital of Columbus
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205-2696
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73190
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425-0721
Country
United States
Facility Name
Vanderbilt Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-6838
Country
United States
Facility Name
Simmons Cancer Center - Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235-9154
Country
United States
Facility Name
Cook Children's Medical Center - Fort Worth
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Texas Children's Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-2399
Country
United States
Facility Name
University of Texas - MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78284-7811
Country
United States
Facility Name
Primary Children's Medical Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States
Facility Name
Children's Hospital and Regional Medical Center - Seattle
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
University of Wisconsin Comprehensive Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Midwest Children's Cancer Center
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Royal Children's Hospital
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
Princess Margaret Hospital for Children
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6001
Country
Australia
Facility Name
Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
Montreal Children's Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3H 1P3
Country
Canada
Facility Name
Hopital Sainte Justine
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1C5
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
17941066
Citation
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.
Results Reference
result

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O6-benzylguanine and Carmustine in Treating Children With Refractory CNS Tumors

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