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- Klinische proef NCT00098761
VNP40101M in Treating Young Patients With Recurrent, Progressive, or Refractory Primary Brain Tumors
Phase I Study Of Cloretazine (VNP40101M) In Children With Recurrent, Progressive Or Refractory Primary Brain Tumors
RATIONALE: Drugs used in chemotherapy, such as VNP40101M, work in different ways to stop tumor cells from dividing so they stop growing or die.
PURPOSE: This phase I trial is studying the side effects and best dose of VNP40101M in treating young patients with recurrent, progressive, or refractory primary brain tumors.
Studie Overzicht
Toestand
Interventie / Behandeling
Gedetailleerde beschrijving
OBJECTIVES:
Primary
- Determine the maximum tolerated dose and dose-limiting toxicity of VNP40101M in pediatric patients with recurrent, progressive, or refractory primary brain tumors.
Secondary
- Determine the pharmacokinetics of this drug and its active metabolite VNP4090CE in these patients.
- Determine the efficacy of this drug in these patients.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to receiving ≥ 1 of the following prior therapies: craniospinal irradiation (yes vs no), autologous bone marrow transplant (yes vs no), and > 2 myelosuppressive chemotherapy or myelosuppressive biologic therapy regimens (yes vs no).
Patients receive VNP40101M IV over 30 minutes on days 1-5. Treatment repeats every 42 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 2-6 patients per stratum receive escalating doses of VNP40101M until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 25% of patients experience dose-limiting toxicity. A total of 12 patients are treated at the MTD.
Patients are followed for 3 months.
PROJECTED ACCRUAL: A total of 4-60 patients (2-30 per stratum) will be accrued for this study within 18 months.
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 1
Contacten en locaties
Studie Locaties
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California
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San Francisco, California, Verenigde Staten, 94115
- UCSF Comprehensive Cancer Center
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District of Columbia
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Washington, District of Columbia, Verenigde Staten, 20010-2970
- Children's National Medical Center
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Illinois
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Chicago, Illinois, Verenigde Staten, 60614
- Children's Memorial Hospital - Chicago
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Massachusetts
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Boston, Massachusetts, Verenigde Staten, 02115
- Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
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North Carolina
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Durham, North Carolina, Verenigde Staten, 27710
- Duke Comprehensive Cancer Center
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Pennsylvania
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Philadelphia, Pennsylvania, Verenigde Staten, 19104-4318
- Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, Verenigde Staten, 15213
- Children's Hospital of Pittsburgh
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Tennessee
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Memphis, Tennessee, Verenigde Staten, 38105
- St. Jude Children's Research Hospital
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Texas
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Houston, Texas, Verenigde Staten, 77030-2399
- Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
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Washington
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Seattle, Washington, Verenigde Staten, 98105
- Children's Hospital and Regional Medical Center - Seattle
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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* primary brain tumor, including benign brain tumors (e.g., low-grade glioma)
- Recurrent or progressive disease OR refractory to standard therapy NOTE: *Patients with intrinsic brain stem or diffuse optic pathway tumors do not require histological confirmation, but must have clinical and/or radiographic evidence of disease progression
- No bone marrow disease
PATIENT CHARACTERISTICS:
Age
- 21 and under
Performance status
- Karnofsky 50-100% (for patients > 16 years of age) OR
- Lansky 50-100% (for patients ≤ 16 years of age)
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count ≥ 1,000/mm^3*
- Platelet count ≥ 100,000/mm^3*
- Hemoglobin ≥ 8 g/dL* NOTE: *Unsupported
Hepatic
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- ALT and AST ≤ 2.5 times ULN
- No overt hepatic disease
Renal
- BUN < 25 mg/dL
- Creatinine ≤ 1.5 times ULN for age OR
- Glomerular filtration rate > 70 mL/min
- No overt renal disease
Cardiovascular
- Shortening fraction ≥ 30% by echocardiogram OR
- Ejection fraction ≥ 50% by gated radionucleotide study
- No clinically significant cardiac arrhythmia by EKG
- No overt cardiac disease
Pulmonary
- DLCO ≥ 60% of predicted
- Chest X-ray normal (defined as absence of pulmonary infiltrates, pneumonitis, pleural effusion, pulmonary hemorrhage, or fibrosis) AND a resting pulse oximetry reading of > 94% in room air (for patients who cannot perform the DLCO)
- No overt pulmonary disease
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Neurologic deficits allowed provided there has been no deficit progression for ≥ 1 week before study entry
- No uncontrolled infection
- No known hypersensitivity to polyethylene glycol
PRIOR CONCURRENT THERAPY:
Biologic therapy
- At least 6 months since prior allogeneic bone marrow or stem cell transplantation
- At least 3 months since prior autologous bone marrow or stem cell transplantation
- More than 1 week since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or epoetin alfa)
- At least 3 weeks since prior myelosuppressive anticancer biologic therapy
- No concurrent routine colony-stimulating factors
Chemotherapy
- At least 3 weeks since prior myelosuppressive anticancer chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
Endocrine therapy
- Concurrent corticosteroids allowed provided dose is stable or decreasing for ≥ 1 week before study entry
Radiotherapy
- At least 3 months since prior craniospinal irradiation ≥ 18 Gy
- At least 2 weeks since prior focal irradiation to the primary tumor and/or symptomatic metastatic sites
Surgery
- Not specified
Other
- At least 7 days since prior nonmyelosuppressive anticancer therapy
- At least 7 days since prior investigational agents
- Concurrent enzyme-inducing anticonvulsant drugs allowed
- No other concurrent anticancer or experimental agents or therapies
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
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Estimate the maximum tolerated dose
Tijdsspanne: First 6 weeks of therapy
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First 6 weeks of therapy
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Number of participants with dose limiting toxicities
Tijdsspanne: First 6 weeks of therapy
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First 6 weeks of therapy
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Pharmacokinetics
Tijdsspanne: Day 1 of therapy
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Plasma samples for pharmacokinetic studies will be collected with the first dose of the study drug pre-infusion, and 5, 15, and 30 minutes, 1 hour, 2 hours, and 4 hours after the end of infusion.
VNP40101M plasma concentration-time data will be modeled and the individual pharmacokinetic pararmeters volume of the central compartment, elimination rate constant, and half-life will be estimated.
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Day 1 of therapy
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Tumor response to VNP40101M
Tijdsspanne: Prior to course 3, 5, and 7 and end of therapy
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MRI of the brain will be obtained prior to couses 3, 5, and 7 and at the end of therapy
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Prior to course 3, 5, and 7 and end of therapy
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Medewerkers en onderzoekers
Sponsor
Medewerkers
Onderzoekers
- Studie stoel: Sri Gururangan, MRCP (UK), Duke University
Publicaties en nuttige links
Studie record data
Bestudeer belangrijke data
Studie start
Primaire voltooiing (Werkelijk)
Studie 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
Trefwoorden
- hooggradig cerebraal astrocytoom bij kinderen
- infratentoriaal ependymoom bij kinderen
- terugkerende kinder supratentoriale primitieve neuroectodermale tumor
- recidiverend cerebellair astrocytoom bij kinderen
- recidiverend cerebraal astrocytoom bij kinderen
- recidiverend ependymoom bij kinderen
- recidiverend hersenstamglioom bij kinderen
- recidiverend medulloblastoom bij kinderen
- terugkerende visuele route in de kindertijd en hypothalamisch glioom
- craniofaryngioom bij kinderen
- kiemceltumor van het centrale zenuwstelsel in de kindertijd
- choroïde plexustumor bij kinderen
- meningeoom van graad I bij kinderen
- meningeoom graad II bij kinderen
- meningeoom graad III bij kinderen
- laaggradig cerebraal astrocytoom bij kinderen
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- CDR0000396779
- PBTC-017
- VION-VNP40101M
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