- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00003288
Tirapazamine Plus Cyclophosphamide in Treating Children With Refractory Solid Tumors
A Trial of Tirapazamine and Cyclophosphamide in Children With Refractory Solid Tumors
Study Overview
Status
Intervention / Treatment
Detailed Description
OBJECTIVES:
I. Determine the maximum tolerated dose and the dose limiting toxicity of tirapazamine when administered with cyclophosphamide as intravenous infusions to children with refractory solid tumors.
II. Determine the incidence and severity of other toxicities of tirapazamine and cyclophosphamide in these patients.
III. Determine a safe and tolerable dose of tirapazamine administered with cyclophosphamide for a phase II study for the same indications.
IV. Determine the pharmacokinetics of tirapazamine in children and adolescents receiving the combination of tirapazamine and cyclophosphamide.
V. Determine the preliminary evidence of antitumor activity of tirapazamine and cyclophosphamide.
OUTLINE: This is a dose escalation study.
Patients receive tirapazamine by 2 hour intravenous infusion (hours 0-2) followed 2 hours later by a 30 minute intravenous infusion of cyclophosphamide. This course is repeated every 3 weeks in patients with partial/complete response or stable disease for a maximum of 1 year. Cohorts of 3-6 patients each are treated at each dose level of tirapazamine. Dose escalation of tirapazamine occurs when 0 of 3 patients or 1 of 6 patients has experienced dose limiting toxicity (DLT). If DLT is experienced in 1 of 3 patients at a given dose level, up to 3 additional patients are treated at that same dose level. If none of the 3 additional patients at that dose level experiences DLT, the dose is escalated. If DLT is experienced in 1 or more of the additional 3 patients, the maximum tolerated dose (MTD) has been exceeded and 3 patients are treated at the next lower dose level (defined as the MTD). A total of six patients are treated at the MTD. If DLT is proved to be neutropenia, patients must then also meet the additional eligibility criteria listed for stratum 2. If neutropenia continues to be the DLT in stratum 2, then additional patients receive subcutaneous filgrastim (granulocyte colony-stimulating factor; G-CSF) beginning 24 hours after cyclophosphamide. A second MTD may be determined for chemotherapy with G-CSF. Patients are followed every 6 months for 4 years, and then annually thereafter.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Ontario
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Toronto, Ontario, Canada, M5G 1X8
- Hospital for Sick Children
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Quebec
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Montreal, Quebec, Canada, H3H 1P3
- Montreal Children's Hospital
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Montreal, Quebec, Canada, H3T 1C5
- Hopital Sainte Justine
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Alabama
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Birmingham, Alabama, United States, 35294
- University of Alabama Comprehensive Cancer Center
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Arkansas
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Little Rock, Arkansas, United States, 72205
- University of Arkansas for Medical Sciences
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California
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La Jolla, California, United States, 92093-0658
- University of California San Diego Cancer Center
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Palo Alto, California, United States, 94304
- Lucile Packard Children's Hospital at Stanford
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Florida
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Miami, Florida, United States, 33136
- Sylvester Cancer Center, University of Miami
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Georgia
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Atlanta, Georgia, United States, 30322
- Emory University Hospital - Atlanta
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Illinois
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Chicago, Illinois, United States, 60614
- Children's Memorial Hospital, Chicago
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Kansas
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Kansas City, Kansas, United States, 66160-7357
- University of Kansas Medical Center
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Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins Oncology Center
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Dana-Farber Cancer Institute
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Boston, Massachusetts, United States, 02111
- Floating Hospital for Children
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Michigan
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Detroit, Michigan, United States, 48201
- Children's Hospital of Michigan
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Mississippi
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Jackson, Mississippi, United States, 39216-4505
- University of Mississippi Medical Center
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
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Saint Louis, Missouri, United States, 63104
- Cardinal Glennon Children's Hospital
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New Jersey
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Hackensack, New Jersey, United States, 07601
- Hackensack University Medical Center
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New York
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Buffalo, New York, United States, 14263-0001
- Roswell Park Cancer Institute
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Syracuse, New York, United States, 13210
- State University of New York - Upstate Medical University
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North Carolina
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Durham, North Carolina, United States, 27710
- Duke Comprehensive Cancer Center
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Tennessee
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Memphis, Tennessee, United States, 38105-2794
- Saint Jude Children's Research Hospital
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Texas
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Dallas, Texas, United States, 75235-9154
- Simmons Cancer Center - Dallas
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Fort Worth, Texas, United States, 76104
- Cook Children's Medical Center - Fort Worth
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Houston, Texas, United States, 77030
- Baylor College of Medicine
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San Antonio, Texas, United States, 78284
- University of Texas Health Science Center at San Antonio
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Wisconsin
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Milwaukee, Wisconsin, United States, 53226
- Midwest Children's Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
DISEASE CHARACTERISTICS:
- Histologically confirmed solid tumor that is refractory to conventional therapy or for which no effective therapy is known
- Brain tumors eligible Brainstem gliomas may waive histological verification requirement
- Neurologic deficits associated with CNS malignancies must be stable for a minimum of 4 weeks prior to study
- No leukemia Stratum 2
- No marrow involvement
PATIENT CHARACTERISTICS:
- Age: 21 and under
- Performance status: Karnofsky or Lansky 50-100%
- Life expectancy: At least 8 weeks
- Absolute neutrophil count at least 1,000/mm3
- Platelet count at least 75,000/mm3
- Hemoglobin at least 9 g/dL
- Bilirubin less than 1.5 mg/dL
- SGPT less than 5 times normal
- Creatinine normal for age OR creatinine clearance at least 70 mL/min
- Shortening fraction at least 27% of normal OR ejection fraction greater than 50% of normal
- Not pregnant or nursing
- Negative pregnancy test required
PRIOR CONCURRENT THERAPY:
- No concurrent anticancer therapy
- At least 6 months since bone marrow transplant and no evidence of graft versus host disease
- At least 1 week since growth factors
- No concurrent granulocyte colony-stimulating factor
- Recovered from prior immunotherapy
- Stratum 2: No prior bone marrow transplantation (with or without total body irradiation)
- At least 6 weeks since prior nitrosourea
- At least 2 weeks since other prior myelosuppressive chemotherapy
- Dexamethasone must be a stable or decreasing dose for 2 weeks prior to study
- Recovered from prior chemotherapy
- Stratum 2: No more than 2 prior chemotherapy regimens
- At least 2 weeks since local palliative radiotherapy (small port)
- At least 6 months since prior substantial bone marrow radiation (e.g., cross- sectional radiotherapy [greater than 24 Gy], total body irradiation, hemi- pelvic radiotherapy)
- Recovered from prior radiotherapy
- Stratum 2: No prior central axis radiation
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm I
See arm description.
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Victor Aquino, MD, Simmons Cancer Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NCI-2012-01837
- POG-9675
- CDR0000066219 (Registry Identifier: PDQ (Physician Data Query))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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