Vorinostat and Alvocidib in Treating Patients With Advanced Solid Tumors
A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Flavopiridol in Advanced Solid Tumors
Descripción general del estudio
Estado
Intervención / Tratamiento
Descripción detallada
OBJECTIVES:
I. Determine the maximum tolerated dose of vorinostat (SAHA) when given in combination with flavopiridol (alvocidib) in patients with advanced solid tumors.
II. Obtain preliminary data on the therapeutic activity of SAHA and flavopiridol in these patients.
III. Evaluate the role of p21, p53, and apoptotic markers relative to treatment response in patients treated with this regimen.
OUTLINE: This is a multicenter, open label, non-randomized, dose-escalation study of vorinostat (SAHA).
Before beginning course 1 of study therapy, patients receive oral SAHA on days 1-3 in order to ensure tolerability of the drug. Beginning 1 week later, patients receive oral SAHA once daily on days 1-3 and 8-10 and fixed-dose alvocidib intravenously (IV) over 1 hour on days 2 and 9. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. An additional 10 patients are treated at the MTD of SAHA in combination with fixed-dose alvocidib. Once the MTD of SAHA in combination with fixed-dose alvocidib is determined, patients receive oral SAHA at one dose level below the MTD once daily on days 1-3 and 8-10 and divided-dose alvocidib IV over 30 minutes followed by alvocidib IV over 4 hours on days 2 and 9. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. If this schedule is well-tolerated, the MTD of SAHA in combination with divided-dose flavopiridol is determined as above. An additional 10 patients are treated at the MTD of SAHA in combination with divided-dose alvocidib. Patients undergo blood draws on days 1 and 9 of course 1 for pharmacokinetic analysis.
After completion of study treatment, patients are followed for 4 weeks.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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New York
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New York, New York, Estados Unidos, 10065
- Memorial Sloan-Kettering Cancer Center
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
Histologically confirmed solid tumor
- Metastatic or unresectable disease
- Standard curative or palliative measures do not exist or are no longer effective
- No hematologic malignancies
- No known brain metastases
- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Bilirubin ≤ 1.5 mg/dL
- AST and ALT ≤ 2.5 times upper limit of normal
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs
No uncontrolled intercurrent illness, including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situations that would preclude study compliance
- Recovered from prior therapy
- At least 2 weeks since prior histone acetylase inhibitors, including valproic acid
- At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- At least 2 weeks since prior investigational therapy
- At least 2 weeks since prior radiotherapy
- No concurrent combination antiretroviral therapy for HIV-positive patients
No concurrent commonly used vitamins, antioxidants, or herbal preparations and supplements
- A single tablet multivitamin is allowed
- No other concurrent anticancer agents or therapies for this mailgnancy
- No other concurrent investigational agents
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Treatment (chemotherapy, enzyme inhibitor)
Before beginning course 1 of study therapy, patients receive oral SAHA on days 1-3 in order to ensure tolerability of the drug.
Beginning 1 week later, patients receive oral SAHA once daily on days 1-3 and 8-10 and fixed-dose alvocidib IV over 1 hour on days 2 and 9. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
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Dado IV
Otros nombres:
Estudios correlativos
Otros nombres:
Administrado oralmente
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Maximum tolerated dose of vorinostat when administered in combination with a fixed dose of weekly flavopiridol
Periodo de tiempo: Course 1
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Defined as the dose one level below the dose at which two or more of the patients in the initial cohort experience dose limiting toxicities (DLT) during the first treatment course.
Graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 Term.
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Course 1
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Clinical pharmacokinetics of vorinostat (SAHA)
Periodo de tiempo: Week 1 of course 1
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Week 1 of course 1
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Therapeutic activity of SAHA and flavopiridol
Periodo de tiempo: Not Provided
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Not Provided
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Expression of p21, p53, and apoptotic markers relative to treatment response
Periodo de tiempo: Baseline to 2 weeks after completion of study treatment
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Evaluated using immunohistochemistry.
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Baseline to 2 weeks after completion of study treatment
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Gary Schwartz, Memorial Sloan Kettering Cancer Center
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (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
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- NCI-2009-00090 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
- U01CA069856 (Subvención/contrato del NIH de EE. UU.)
- P30CA008748 (Subvención/contrato del NIH de EE. UU.)
- 6858 (Otro identificador: CTEP)
- 05-109 (Otro identificador: Memorial Sloan-Kettering Cancer Center)
- MSKCC-05109
- CDR0000472411
- NCI-6858
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