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

29 de junho de 2011 atualizado por: 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.

Visão geral do estudo

Status

Concluído

Condições

Tumores cerebrais e do sistema nervoso central

Intervenção / Tratamento

Medicamento: laromustine

Descrição detalhada

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.

Tipo de estudo

Intervencional

Inscrição (Real)

Estágio

Fase 1

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

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

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

Não mais velho que 21 anos (Filho, Adulto)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

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

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

Finalidade Principal: Tratamento
Alocação: N / D
Modelo Intervencional: Atribuição de grupo único
Mascaramento: Nenhum (rótulo aberto)

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado	Prazo
Estimate the maximum tolerated dose Prazo: First 6 weeks of therapy	First 6 weeks of therapy
Number of participants with dose limiting toxicities Prazo: First 6 weeks of therapy	First 6 weeks of therapy

Medidas de resultados secundários

Medida de resultado	Descrição da medida	Prazo
Pharmacokinetics Prazo: 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 Prazo: 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

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Pediatric Brain Tumor Consortium

Colaboradores

National Cancer Institute (NCI)

Investigadores

Cadeira de estudo: Sri Gururangan, MRCP (UK), Duke University

Publicações e links úteis

A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.

Publicações Gerais

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.

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo

1 de fevereiro de 2005

Conclusão Primária (Real)

1 de outubro de 2006

Conclusão do estudo (Real)

1 de fevereiro de 2008

Datas de inscrição no estudo

Enviado pela primeira vez

8 de dezembro de 2004

Enviado pela primeira vez que atendeu aos critérios de CQ