Colony-Stimulating Factors in Treating Children With Recurrent or Refractory Solid Tumors
A Phase I Study of Thrombopoietin (rhTPO) Plus G-CSF in Children Receiving Ifosfamide, Carboplatin, and Etoposide (I.C.E.) Chemotherapy for Recurrent or Refractory Solid Tumors
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as thrombopoietin and G-CSF may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy.
PURPOSE: Phase I trial to study the effectiveness of colony-stimulating factors in treating children who have recurrent or refractory solid tumors and who are receiving chemotherapy.
Visão geral do estudo
Status
Condições
Descrição detalhada
OBJECTIVES:
- Determine the pharmacokinetics and toxicities associated with the administration of recombinant human thrombopoietin in children with solid tumors receiving myelosuppressive chemotherapy with ifosfamide, carboplatin, and etoposide (ICE).
- Determine a safe dose of recombinant human thrombopoietin with filgrastim (G-CSF) in this patient population.
- Evaluate the time to platelet count recovery following chemotherapy in this patient population.
- Evaluate the depth and duration of neutropenia and thrombocytopenia and the number of platelet transfusion events in this patient population.
OUTLINE: This is a dose escalation study of recombinant human thrombopoietin.
All patients receive chemotherapy consisting of carboplatin IV over 60 minutes on days 0 and 1 and etoposide and ifosfamide IV over 60 minutes on days 0-4. Chemotherapy is continued in the absence of disease progression or unacceptable toxicity for a maximum of 6 courses every 21 days.
Cohorts of 3-6 patients each receive escalating doses of recombinant human thrombopoietin IV on days 4, 6, 8, 10, and 12 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which fewer than 2 patients experience dose limiting toxicity. After the MTD is determined an additional cohort of patients are treated at this dose level every other day on days 4-20. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 5 and continuing until absolute neutrophil count is greater than 1000/mm3 for 2 consecutive days or day 33.
PROJECTED ACCRUAL: A total of 24 evaluable patients will be accrued for this study.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 1
Contactos e Locais
Locais de estudo
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Western Australia
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Perth, Western Australia, Austrália, 6001
- Princess Margaret Hospital for Children
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California
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Long Beach, California, Estados Unidos, 90806
- Long Beach Memorial Medical Center
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Los Angeles, California, Estados Unidos, 90095-1781
- Jonsson Comprehensive Cancer Center, UCLA
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Los Angeles, California, Estados Unidos, 91010
- Beckman Research Institute, City of Hope
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Los Angeles, California, Estados Unidos, 90027-0700
- Children's Hospital Los Angeles
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Orange, California, Estados Unidos, 92668
- Children's Hospital of Orange County
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San Francisco, California, Estados Unidos, 94115-0128
- UCSF Cancer Center and Cancer Research Institute
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District of Columbia
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Washington, District of Columbia, Estados Unidos, 20010-2970
- Children's National Medical Center
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Indiana
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Indianapolis, Indiana, Estados Unidos, 46202-5265
- Indiana University Cancer Center
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Michigan
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Ann Arbor, Michigan, Estados Unidos, 48109-0752
- University of Michigan Comprehensive Cancer Center
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Minnesota
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Minneapolis, Minnesota, Estados Unidos, 55455
- University of Minnesota Cancer Center
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Rochester, Minnesota, Estados Unidos, 55905
- Mayo Clinic Cancer Center
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Missouri
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Kansas City, Missouri, Estados Unidos, 64108
- Children's Mercy Hospital - Kansas City
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New York
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New York, New York, Estados Unidos, 10021
- Memorial Sloan-Kettering Cancer Center
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New York, New York, Estados Unidos, 10016
- Kaplan Cancer Center
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New York, New York, Estados Unidos, 10032
- Herbert Irving Comprehensive Cancer Center
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Ohio
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Cincinnati, Ohio, Estados Unidos, 45229-3039
- Children's Hospital Medical Center - Cincinnati
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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos, 19104
- Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, Estados Unidos, 15213
- Children's Hospital of Pittsburgh
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Tennessee
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Nashville, Tennessee, Estados Unidos, 37232-6838
- Vanderbilt Cancer Center
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Texas
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Houston, Texas, Estados Unidos, 77030
- University of Texas - MD Anderson Cancer Center
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Utah
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Salt Lake City, Utah, Estados Unidos, 84132
- Huntsman Cancer Institute
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Washington
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Seattle, Washington, Estados Unidos, 98105
- Children's Hospital and Regional Medical Center - Seattle
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Wisconsin
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Madison, Wisconsin, Estados Unidos, 53792
- University of Wisconsin Comprehensive Cancer Center
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
DISEASE CHARACTERISTICS: Histologically proven (except for brain stem tumors) malignancy that has
failed or relapsed after standard first-line antineoplastic therapy
- Sarcoma (soft tissue and bone)
- Kidney tumors
- Brain tumors
- Other solid tumors (gonadal and germ cell tumors, malignant melanoma,
- retinoblastoma, liver tumors, and miscellaneous tumors) Must have had recurrence within the past 4 weeks
No bone marrow involvement
No prior or concurrent myelogenous leukemia
PATIENT CHARACTERISTICS:
Age:
- 1 to 21
Performance status:
- Lansky or Karnofsky 60-100%
Life expectancy:
- At least 12 weeks
Hematopoietic:
- Absolute neutrophil count greater than 1000/mm3
- Platelet count greater than 100,000/mm3
- No grade III or IV thrombosis
Hepatic:
- Bilirubin less than 1.5 times upper limit of normal (ULN)
- SGOT or SGPT less than 2.5 times ULN
Renal:
- Creatinine clearance or glomerular filtration rate at least 70 mL/min
Cardiovascular:
- Ejection fraction normal
- No evidence of arrhythmias requiring therapy
- Fractional shortening greater than 28%
Other:
- Not pregnant or nursing
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- At least 10 days since prior colony-stimulating factor therapy and recovered
- At least 30 days since prior epoetin alfa
- No other concurrent cytokines, including epoetin alfa
Chemotherapy:
- At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) and
- recovered
- At least 3 months since therapy with etoposide, carboplatin, or ifosfamide
- that is identical to study treatment
Endocrine therapy:
- Not specified
Radiotherapy:
- Concurrent radiotherapy allowed after third course of therapy
- No prior cranial/spinal radiotherapy
- No prior radiotherapy to greater than 50% of bone marrow
Surgery:
- Concurrent surgery allowed after the second course of therapy
Other:
- No concurrent investigational agents
- No concurrent lithium, aspirin, coumadin, or heparin
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Cuidados de suporte
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: Cohort 1
Chemotherapy days 0-4, G-CSF (5 μg/kg/d) as a daily subcutaneous injection beginning on Day 5.
All patients receive recombinant human thrombopoietin (rhTPO).
rhTPO began on the last day of ICE (Ifosfamide, Carboplatin and Etoposide) chemotherapy (Day 4) and subsequent doses will be administered on Days 6, 8, 10 and 12 (5 doses total).
The initial dose of rhTPO was 1.2 μg/kg/dose and was subsequently escalated to 2.4 and 3.6 μg/kg/dose as tolerated.
Therapy will continue for maximum six courses.
Pharmacokinetic data will be obtained (during course one only).
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Experimental: Cohort 2
Chemotherapy days 0-4, G-CSF (5 μg/kg/d) as a daily subcutaneous injection beginning on Day 5. All patients receive recombinant human thrombopoietin (rhTPO). The dose of rhTPO 1.2 μg/kg/dose and subsequently escalated to 2.4 and 3.6 μg/kg/dose as tolerated. Patients assigned to Cohort II will receive pre-chemotherapy rhTPO at 3.6 μg/kg/dose on Days -5, -3, -1, and post-chemotherapy rhTPO on Days +4, +6, and +8 (6 doses total. Subsequent courses of chemotherapy will begin as soon as the ANC recovers to ≥ 1,000/μL and the platelet count to ≥ 100,000/μL between days 21 and 35. Therapy will continue for maximum six courses. Pharmacokinetic data will be obtained (during course one nly). For the second cohort, full data collection will occur for cycles one and two and limited data collection for cycles 3, 4, 5, and 6. |
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Determine the pharmacokinetics and toxicities associated with the administration of recombinant human thrombopoietin (rhTPO)
Prazo: length of study
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To determine the pharmacokinetics and toxicities associated with the administration of recombinant human thrombopoietin (rhTPO) in children receiving I.C.E.
myelosuppressive chemotherapy.
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length of study
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Evaluate the time for patients to demonstrate platelet recovery
Prazo: Length of study
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To evaluate the time for patients to demonstrate platelet recovery following I.C.E.
chemotherapy with rhTPO + G-CSF.
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Length of study
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Cadeira de estudo: Mitchell S. Cairo, MD, Herbert Irving Comprehensive Cancer Center
Publicações e links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
- câncer de células renais recorrente
- tumor sólido infantil não especificado, protocolo específico
- neutropenia
- melanoma recorrente
- melanoma intraocular recorrente
- trombocitopenia
- rabdomiossarcoma infantil recorrente
- neuroblastoma recorrente
- sarcoma uterino recorrente
- tumor de células germinativas de ovário recorrente
- tumor de células germinativas testiculares maligno recorrente
- sarcoma de Ewing recorrente/tumor neuroectodérmico primitivo periférico
- osteossarcoma recorrente
- tumor de Wilms recorrente e outros tumores renais da infância
- Tumor neuroectodérmico primitivo supratentorial recorrente da infância
- astrocitoma cerebelar infantil recorrente
- astrocitoma cerebral infantil recorrente
- tumor extragonadal de células germinativas
- câncer de fígado infantil recorrente
- sarcoma recorrente de tecidos moles na infância
- glioma do tronco cerebral recorrente na infância
- meduloblastoma infantil recorrente
- tumor de células germinativas do sistema nervoso central na infância
- tumor de células germinativas na infância
- retinoblastoma recorrente
- tumor trofoblástico gestacional recorrente
- glioma recorrente da via visual na infância
Termos MeSH relevantes adicionais
- Processos Patológicos
- Atributos da doença
- Recorrência
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Inibidores Enzimáticos
- Agentes Antineoplásicos
- Fatores imunológicos
- Agentes Antineoplásicos Alquilantes
- Agentes Alquilantes
- Agentes Antineoplásicos Fitogênicos
- Inibidores da Topoisomerase II
- Inibidores da Topoisomerase
- Adjuvantes Imunológicos
- Carboplatina
- Etoposídeo
- Ifosfamida
- Lenograstim
Outros números de identificação do estudo
- 09717
- CCG-09717
- CDR0000066668
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