Tirapazamine Plus Cyclophosphamide in Treating Children With Refractory Solid Tumors

NCT ID: NCT00003288

Last Updated: 2013-02-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

1998-08-31

Brief Summary

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Phase I trial to study the effectiveness of tirapazamine plus cyclophosphamide in treating children who have refractory solid 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

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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.

Conditions

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Unspecified Childhood Solid Tumor, Protocol Specific

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm I

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Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

cyclophosphamide

Intervention Type DRUG

tirapazamine

Intervention Type DRUG

Interventions

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filgrastim

Intervention Type BIOLOGICAL

cyclophosphamide

Intervention Type DRUG

tirapazamine

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Victor Aquino, MD

Role: STUDY_CHAIR

Simmons Cancer Center

Locations

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University of Alabama Comprehensive Cancer Center

Birmingham, Alabama, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

University of California San Diego Cancer Center

La Jolla, California, United States

Site Status

Lucile Packard Children's Hospital at Stanford

Palo Alto, California, United States

Site Status

Sylvester Cancer Center, University of Miami

Miami, Florida, United States

Site Status

Emory University Hospital - Atlanta

Atlanta, Georgia, United States

Site Status

Children's Memorial Hospital, Chicago

Chicago, Illinois, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Johns Hopkins Oncology Center

Baltimore, Maryland, United States

Site Status

Floating Hospital for Children

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Children's Hospital of Michigan

Detroit, Michigan, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Cardinal Glennon Children's Hospital

St Louis, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

State University of New York - Upstate Medical University

Syracuse, New York, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

Saint Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Simmons Cancer Center - Dallas

Dallas, Texas, United States

Site Status

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Midwest Children's Cancer Center

Milwaukee, Wisconsin, United States

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Montreal Children's Hospital

Montreal, Quebec, Canada

Site Status

Hopital Sainte Justine

Montreal, Quebec, Canada

Site Status

Countries

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United States Canada

Other Identifiers

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POG-9675

Identifier Type: -

Identifier Source: secondary_id

CDR0000066219

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-01837

Identifier Type: -

Identifier Source: org_study_id

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