Tirapazamine Plus Cyclophosphamide in Treating Children With Refractory Solid Tumors
A Trial of Tirapazamine and Cyclophosphamide in Children With Refractory Solid Tumors
Studie Overzicht
Toestand
Interventie / Behandeling
Gedetailleerde beschrijving
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.
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 1
Contacten en locaties
Studie Locaties
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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, Verenigde Staten, 35294
- University of Alabama Comprehensive Cancer Center
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Arkansas
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Little Rock, Arkansas, Verenigde Staten, 72205
- University of Arkansas for Medical Sciences
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California
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La Jolla, California, Verenigde Staten, 92093-0658
- University of California San Diego Cancer Center
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Palo Alto, California, Verenigde Staten, 94304
- Lucile Packard Children's Hospital at Stanford
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Florida
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Miami, Florida, Verenigde Staten, 33136
- Sylvester Cancer Center, University of Miami
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Georgia
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Atlanta, Georgia, Verenigde Staten, 30322
- Emory University Hospital - Atlanta
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Illinois
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Chicago, Illinois, Verenigde Staten, 60614
- Children's Memorial Hospital, Chicago
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Kansas
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Kansas City, Kansas, Verenigde Staten, 66160-7357
- University of Kansas Medical Center
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Maryland
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Baltimore, Maryland, Verenigde Staten, 21287
- Johns Hopkins Oncology Center
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Massachusetts
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Boston, Massachusetts, Verenigde Staten, 02115
- Dana-Farber Cancer Institute
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Boston, Massachusetts, Verenigde Staten, 02111
- Floating Hospital for Children
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Michigan
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Detroit, Michigan, Verenigde Staten, 48201
- Children's Hospital of Michigan
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Mississippi
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Jackson, Mississippi, Verenigde Staten, 39216-4505
- University of Mississippi Medical Center
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Missouri
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Saint Louis, Missouri, Verenigde Staten, 63110
- Washington University School of Medicine
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Saint Louis, Missouri, Verenigde Staten, 63104
- Cardinal Glennon Children's Hospital
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New Jersey
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Hackensack, New Jersey, Verenigde Staten, 07601
- Hackensack University Medical Center
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New York
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Buffalo, New York, Verenigde Staten, 14263-0001
- Roswell Park Cancer Institute
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Syracuse, New York, Verenigde Staten, 13210
- State University of New York - Upstate Medical University
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North Carolina
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Durham, North Carolina, Verenigde Staten, 27710
- Duke Comprehensive Cancer Center
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Tennessee
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Memphis, Tennessee, Verenigde Staten, 38105-2794
- Saint Jude Children's Research Hospital
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Texas
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Dallas, Texas, Verenigde Staten, 75235-9154
- Simmons Cancer Center - Dallas
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Fort Worth, Texas, Verenigde Staten, 76104
- Cook Children's Medical Center - Fort Worth
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Houston, Texas, Verenigde Staten, 77030
- Baylor College of Medicine
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San Antonio, Texas, Verenigde Staten, 78284
- University of Texas Health Science Center at San Antonio
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Wisconsin
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Milwaukee, Wisconsin, Verenigde Staten, 53226
- Midwest Children's Cancer Center
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
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Experimenteel: Arm I
See arm description.
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Medewerkers en onderzoekers
Sponsor
Onderzoekers
- Studie stoel: Victor Aquino, MD, Simmons Cancer Center
Studie record data
Bestudeer belangrijke data
Studie start
Primaire voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Schatting)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Neoplasmata
- Fysiologische effecten van medicijnen
- Moleculaire mechanismen van farmacologische werking
- Antireumatische middelen
- Antineoplastische middelen
- Immunosuppressieve middelen
- Immunologische factoren
- Antineoplastische middelen, alkylering
- Alkyleringsmiddelen
- Myeloablatieve agonisten
- Cyclofosfamide
- Tirapazamine
Andere studie-ID-nummers
- NCI-2012-01837
- POG-9675
- CDR0000066219 (Register-ID: PDQ (Physician Data Query))
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