- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00030108
Ixabepilone in Treating Young Patients With Solid Tumors or Leukemia That Haven't Responded to Therapy
Phase I Trial and Pharmacokinetic Study of BMS-247550 (NSC 710428, Ixabepilone), an Epothilone B Analog, in Pediatric Patients With Refractory Solid Tumors and Leukemias
RATIONALE: Drugs used in chemotherapy use 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 ixabepilone in treating young patients with relapsed or refractory solid tumors or leukemia.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
OBJECTIVES:
Primary
- Determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of ixabepilone in young patients with refractory solid tumors (closed to accrual as of 10/4/2007) or relapsed or refractory leukemia.
- Determine the toxicity spectrum of this drug in these patients.
- Determine the plasma pharmacokinetics of this drug in these patients.
- Determine the pharmacodynamics of this drug in these patients.
- Assess the nerve growth factor levels, before and after the initiation of this drug, as a potential surrogate marker for the development of peripheral neuropathy in these patients.
Secondary
- Determine the response of patients treated with this drug.
- Compare the tolerability, toxicity profile, MTD, DLT, pharmacokinetics, and pharmacodynamics of this drug in young patients treated on this study vs adults with solid tumors (closed to accrual as of 10/4/2007) treated on the ongoing Medicine Branch, NCI, phase I study.
- Assess the safety and tolerability of ixabepilone at the solid tumor MTD (expanded leukemia cohort).
- Evaluate the plasma pharmacokinetics of in young patients with refractory or relapsed leukemia.
- Evaluate the extent of tubulin polymerization in leukemic blasts at baseline after treatment with ixabepilone ex-vivo.
- Compare the effects of tubulin polymerization in leukemic blasts with ixabepilone versus paclitaxel ex-vivo with an without the presence of a potent P-glycoprotein inhibitor.
- Evaluate the activity known drug transporters in drug-resistant leukemias in leukemic blasts.
OUTLINE: This is a multicenter, dose-escalation study.
Patients receive ixabepilone IV over 1 hour on days 1-5. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of ixabepilone until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 or more of 6 patients experience dose-limiting toxicity. Intrapatient dose escalation to one dose level above the enrollment dose level is allowed in patients who have stable or responding disease or are experiencing other benefits from therapy (e.g., decrease in tumor-related pain symptoms) and who have no grade 2 or greater non-hematologic toxicity and no grade 3 or greater hematologic toxicity. Additional patients are treated at the MTD. Patients treated at the MTD may not undergo intrapatient dose escalation.
PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study within 1-2 years.
Tipo de estudio
Inscripción (Anticipado)
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
District of Columbia
-
Washington, District of Columbia, Estados Unidos, 20010-2970
- Children's National Medical Center
-
-
Maryland
-
Bethesda, Maryland, Estados Unidos, 20892-1182
- Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
DISEASE CHARACTERISTICS:
Meets 1 of the following criteria:
Histologically confirmed solid tumor (closed to accrual as of 10/4/2007) that relapsed after or failed to respond to front-line curative therapy and for which no other potentially curative treatment options exist
- Curative therapy may include surgery, radiotherapy, chemotherapy, or any combination of these modalities
Eligible tumor types include, but are not limited to, the following:
- Rhabdomyosarcoma
- Other soft tissue sarcomas
- Ewing's sarcoma family of tumors
- Osteosarcoma
- Neuroblastoma
- Wilms' tumor
- Hepatic tumors
- Germ cell tumors
Primary brain tumors
- Histologic confirmation may be waived for brain stem or optic glioma
Diagnosis of relapsed or refractory leukemia
- Patients with refractory or second or greater relapsed leukemia must have > 25% blasts in the bone marrow (M3 bone marrow) with or without active extramedullary disease (except for leptomeningeal disease)
- Relapsed after or failed to respond to frontline curative therapy and no other potentially curative therapy (e.g., radiotherapy, chemotherapy, or any combination of these modalities) exists
- Patients with acute promyelocytic leukemia must be refractory to treatment with retinoic acid and arsenic trioxide
- Patients with Philadelphia chromosome positive chronic myelogenous leukemia must be refractory to imatinib
- No active CNS leukemia (CNS3)
PATIENT CHARACTERISTICS:
Age:
- 2 to 18 (solid tumor patients [closed to accrual as of 10/4/2007])
- 1 to 21 (leukemia patients)
Performance status:
For patients age 11 to 21:
- Karnofsky 50-100%
For patients age 1 to 10:
- Lansky 50-100%
Life expectancy:
- Not specified
Hematopoietic:
- Platelet count at least 100,000/mm^3 (20,000/mm^3 for leukemia patients)
- Hemoglobin ≥ 8.0 g/dL
Hepatic:
- Bilirubin less than 1.5 times upper limit of normal (ULN)
- SGOT and SGPT less than 2.5 times ULN
- No hepatic dysfunction that would preclude study
Renal:
- Creatinine normal for age OR
- Creatinine clearance at least 60 mL/min
- No renal dysfunction that would preclude study
Other:
- No known severe prior hypersensitivity reaction to agents containing Cremophor EL
- No clinically significant unrelated systemic illness (e.g., serious infections or other organ dysfunction) that would preclude study
- No grade 2 or greater preexisting sensory neuropathy
- More than 2 month since prior and no concurrent evidence of graft vs host disease
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Recovered from all therapy-related acute toxic effects (leukemia patients only)
- Prior epoetin alfa allowed
- At least 3 days since other prior colony-stimulating factors (e.g., filgrastim (G-CSF), sargramostim (GM-CSF), or interleukin-11 (IL-11))
- At least 6 months since prior bone marrow transplantation
- At least 2 months since prior stem cell transplantation or rescue (leukemia patients)
- At least 7 days since prior therapy with a biological agent and hematopoietic growth factor with the exception of erythropoietin
- More than 3 weeks since prior monoclonal antibody therapy (leukemia patients only)
- No concurrent GM-CSF or IL-11
- No concurrent immunotherapy
Chemotherapy:
- See Disease Characteristics
- Recovered from all therapy-related acute toxic effects (leukemia patients only)
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
- No other concurrent anticancer chemotherapy
Endocrine therapy:
- Concurrent corticosteroids allowed for the control of symptoms related to tumor-associated edema in patients with brain tumors
- Patients with brain tumors must be on a stable or tapering dose of corticosteroids for 7 days before baseline scan is performed for the purpose of assessing response to study therapy
- Must be on a stable or tapering dose of corticosteroids for 7 days prior to study entry (leukemia patients only)
Radiotherapy:
- See Disease Characteristics
- Recovered from all therapy-related acute toxic effects (leukemia patients only)
- At least 4 weeks since prior radiotherapy
- More than 2 weeks since prior local palliative radiotherapy (leukemia patients only)
- More than 3 months since prior total-body irradiation, craniospinal radiotherapy, or radiotherapy to ≥50% of the pelvis (leukemia patients only)
- More than 6 weeks since prior other substantial bone marrow radiotherapy (leukemia patients only)
- No prior extensive radiotherapy (e.g., craniospinal irradiation, total body irradiation, or radiotherapy to more than half of the pelvis)
- No concurrent anticancer radiotherapy
Surgery:
- See Disease Characteristics
Other:
- Recovered from prior therapy
- At least 30 days since any prior investigational anticancer therapy
At least 1 week since prior known inhibitors of CYP3A4, including any of the following:
- Antibiotics (i.e., clarithromycin, erythromycin, or troleandomycin)
- Anti-HIV agents (i.e, delaviridine, nelfinavir, amprenavir, ritonavir, idinavir, saquinavir, or lopinavir)
- Anti-fungals (i.e., itraconazole, ketoconazole, fluconazole [doses > 3mg/kg/day], or voriconazole)
- Anti-depressants (i.e., nefaxodone or fluovoxamine)
- Calcium channel blockers (i.e., verapamil or diltiazem)
- Anti-emetics (i.e., aprepitant [Emend®])
- Miscellaneous agents (i.e., amiodarone)
- Grapefruit juice
- No other concurrent investigational agents
- No concurrent St. John's Wort
- No concurrent known inhibitors of CYP3A4, including grapefruit juice
- Concurrent other agents inducing CYP3A4 allowed
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
---|
Maximum tolerated dose and dose-limiting toxicity of ixabepilone
|
Toxicity spectrum
|
Plasma pharmacokinetics
|
Farmacodinamia
|
Nerve growth factor levels before and after drug administration
|
Medidas de resultado secundarias
Medida de resultado |
---|
Respuesta tumoral objetiva
|
Tubulin polymerization in PBMCs prior to the start of the infusion, just before the end of the infusion, 5 hours after the end of the infusion and before the start of the infusion on day 2 of the ixabepilone on course 1
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Silla de estudio: AeRang Kim, MD, National Cancer Institute (NCI)
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
- tumor sólido infantil no especificado, protocolo específico
- Leucemia linfoblástica aguda infantil L3
- Leucemia linfoblástica aguda infantil de células B
- leucemia mieloide aguda infantil en remisión
- leucemia mieloide cronica infantil
- leucemia mielógena crónica, BCR-ABL1 positivo
- rabdomiosarcoma infantil previamente tratado
- Rabdomiosarcoma infantil recurrente
- neuroblastoma recurrente
- leucemia linfoblástica aguda infantil recurrente
- Leucemia linfoblástica aguda infantil L1
- Leucemia linfoblástica aguda infantil L2
- leucemia mieloide aguda infantil recurrente
- sarcoma de Ewing recurrente/tumor neuroectodérmico primitivo periférico
- osteosarcoma recurrente
- Tumor de Wilms recurrente y otros tumores renales infantiles
- leucemia promielocítica aguda infantil (M3)
- oligodendroglioma infantil
- astrocitoma cerebeloso infantil recurrente
- astrocitoma cerebral infantil recurrente
- ependimoma infantil recurrente
- cáncer de hígado infantil recurrente
- sarcoma de tejido blando infantil recurrente
- meduloblastoma infantil recurrente
- vía visual infantil recurrente y glioma hipotalámico
- craneofaringioma infantil
- tumor de células germinales del sistema nervioso central infantil
- tumor de células germinales infantil
- tumor del plexo coroideo infantil
- meningioma infantil grado I
- meningioma infantil grado II
- meningioma infantil grado III
- teratoma infantil
- tumor testicular maligno de células germinativas infantil
- tumor maligno de células germinales de ovario infantil
- tumor extragonadal de células germinales infantil
- Tumor maligno de células germinativas infantil recidivante
- leucemia basófila aguda infantil
- leucemia eosinofílica aguda infantil
- leucemia linfoblástica aguda infantil
- leucemia linfoblástica aguda infantil no T, no B, cALLa negativa
- Leucemia linfoblástica aguda infantil no T, no B, cALLa positiva
- leucemia linfoblástica aguda infantil no T, no B, cALLa positiva, pre-B
- Leucemia linfoblástica aguda infantil TdT negativa
- Leucemia linfoblástica aguda infantil TdT positiva
Términos MeSH relevantes adicionales
- Enfermedades del Sistema Digestivo
- Enfermedades del Sistema Nervioso
- Neoplasias De Tejidos Conectivos Y Blandos
- Neoplasias por tipo histológico
- Neoplasias por sitio
- Neoplasias Glandulares y Epiteliales
- Neoplasias del Sistema Digestivo
- Enfermedades del HIGADO
- Neoplasias Neuroepiteliales
- Tumores neuroectodérmicos
- Neoplasias De Tejido Nervioso
- Tumores Neuroectodérmicos Primitivos
- Tumores Neuroectodérmicos Primitivos Periféricos
- Neoplasias
- Sarcoma
- Neoplasias De Células Germinales Y Embrionarias
- Leucemia
- Neoplasias del Sistema Nervioso
- Neoplasias del Sistema Nervioso Central
- Neoplasias Hepaticas
- Neuroblastoma
Otros números de identificación del estudio
- 020031
- 02-C-0031
- NCI-5425
- CDR0000069133
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .