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VNP40101M in Treating Young Patients With Recurrent, Progressive, or Refractory Primary Brain Tumors

29. juni 2011 oppdatert av: Pediatric Brain Tumor Consortium

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.

Studieoversikt

Status

Fullført

Forhold

Svulster i hjernen og sentralnervesystemet

Intervensjon / Behandling

Legemiddel: laromustine

Detaljert beskrivelse

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

Intervensjonell

Registrering (Faktiske)

Fase

Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

Forente stater
- California
  - San Francisco, California, Forente stater, 94115
    - UCSF Comprehensive Cancer Center
- District of Columbia
  - Washington, District of Columbia, Forente stater, 20010-2970
    - Children's National Medical Center
- Illinois
  - Chicago, Illinois, Forente stater, 60614
    - Children's Memorial Hospital - Chicago
- Massachusetts
  - Boston, Massachusetts, Forente stater, 02115
    - Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
- North Carolina
  - Durham, North Carolina, Forente stater, 27710
    - Duke Comprehensive Cancer Center
- Pennsylvania
  - Philadelphia, Pennsylvania, Forente stater, 19104-4318
    - Children's Hospital of Philadelphia
  - Pittsburgh, Pennsylvania, Forente stater, 15213
    - Children's Hospital of Pittsburgh
- Tennessee
  - Memphis, Tennessee, Forente stater, 38105
    - St. Jude Children's Research Hospital
- Texas
  - Houston, Texas, Forente stater, 77030-2399
    - Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
- Washington
  - Seattle, Washington, Forente stater, 98105
    - Children's Hospital and Regional Medical Center - Seattle

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

Ikke eldre enn 21 år (Barn, Voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

Primært formål: Behandling
Tildeling: N/A
Intervensjonsmodell: Enkeltgruppeoppdrag
Masking: Ingen (Open Label)

Hva måler studien?

Primære resultatmål

Resultatmål	Tidsramme
Estimate the maximum tolerated dose Tidsramme: First 6 weeks of therapy	First 6 weeks of therapy
Number of participants with dose limiting toxicities Tidsramme: First 6 weeks of therapy	First 6 weeks of therapy

Sekundære resultatmål

Resultatmål	Tiltaksbeskrivelse	Tidsramme
Pharmacokinetics Tidsramme: Day 1 of therapy	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.	Day 1 of therapy
Tumor response to VNP40101M Tidsramme: Prior to course 3, 5, and 7 and end of therapy	MRI of the brain will be obtained prior to couses 3, 5, and 7 and at the end of therapy	Prior to course 3, 5, and 7 and end of therapy

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Pediatric Brain Tumor Consortium

Samarbeidspartnere

National Cancer Institute (NCI)

Etterforskere

Studiestol: Sri Gururangan, MRCP (UK), Duke University

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Gururangan S, Turner CD, Stewart CF, O'Shaughnessy M, Kocak M, Poussaint TY, Phillips PC, Goldman S, Packer R, Pollack IF, Blaney SM, Karsten V, Gerson SL, Boyett JM, Friedman HS, Kun LE. Phase I trial of VNP40101M (Cloretazine) in children with recurrent brain tumors: a pediatric brain tumor consortium study. Clin Cancer Res. 2008 Feb 15;14(4):1124-30. doi: 10.1158/1078-0432.CCR-07-4242.

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. februar 2005

Primær fullføring (Faktiske)

1. oktober 2006

Studiet fullført (Faktiske)

1. februar 2008

Datoer for studieregistrering

Først innsendt

8. desember 2004

Først innsendt som oppfylte QC-kriteriene