- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00068484
A Dose Finding Phase I Trial of the Combination of Topotecan and PS-341, a Novel Proteasome Inhibitor, in Advanced Malignancies
Descripción general del estudio
Estado
Descripción detallada
PRIMARY OBJECTIVES:
I. Determine the safety of the combination of PS-341 and topotecan. II. Determine the dose limiting toxicities and maximum tolerated dose as well as the recommended phase II doses of the combination.
III. Assess the pharmacokinetics of topotecan alone and in combination with PS-341.
SECONDARY OBJECTIVES:
I. Estimate the objective response rate of a combination of PS-341 and topotecan delivered on days 1-5 every three weeks as defined by the RECIST criteria.
II. Assess the pharmacodynamics of topo I levels. III. Determine the expression of the DNA repair enzyme XRCC1 in tumor biopsies.
OUTLINE: This is a dose-escalation study.
Patients receive topotecan IV over 30 minutes on days 1-5. Beginning with course 2, patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of topotecan and bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experience dose-limiting toxicity.
PROJECTED ACCRUAL: A total of 20-25 patients will be accrued for this study.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Connecticut
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New Haven, Connecticut, Estados Unidos, 06520-8032
- Yale University
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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:
- Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
- Tumor accessible to core needle biopsy and willingness to undergo this procedure prior to the start of treatment
- Evaluable disease as defined in the RECIST criteria
- ECOG performance status =< 2
- Life expectancy of greater than 3 months
- Absolute neutrophil count > 1,500/ul
- Platelets > 100,000/ul
- Total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal
- Creatinine < 2.0 mg/ml
- Ability to understand and the willingness to sign a written informed consent document
- Metastatic brain or meningeal tumors are allowed if the patient is > 1 month from surgery and/or radiation and is clinically stable with respect to the tumor at the time of the study entry and currently off corticosteroids
- Pregnancy test for pre-menopausal women
- The effects of PS-341 and topotecan on the developing human fetus are unknown; for this reason women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Exclusion Criteria:
- Creatinine clearance < 40 mL/min
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
- Those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to topotecan, PS-341 or other agents used in this study
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study because topotecan is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with topotecan and PS-341, breastfeeding should be discontinued; these potential risks may also apply to other agents used in this study
- Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with topotecan and PS-341 or other agents administered during the study.; appropriate studies will be undertaken for patients receiving combination anti-retroviral therapy when indicated
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 |
---|---|
Experimental: Treatment (topotecan hydrochloride, bortezomib)
Patients receive topotecan IV over 30 minutes on days 1-5.
Beginning with course 2, patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11.
Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
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Estudios correlativos
Dado IV
Otros nombres:
Estudios correlativos
Otros nombres:
Dado IV
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
---|---|
Dose limiting toxicities
Periodo de tiempo: Up to 3 years
|
Up to 3 years
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Maximum tolerated dose (MTD)
Periodo de tiempo: 21 days
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21 days
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Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
---|---|
Pharmacokinetics of topotecan hydrochloride
Periodo de tiempo: 5 minutes immediately after sample collection
|
5 minutes immediately after sample collection
|
Levels of topoisomerase I
Periodo de tiempo: Up to 3 years
|
Up to 3 years
|
DNA repair enzymes
Periodo de tiempo: Up to 3 years
|
Up to 3 years
|
Objective response according to the RECIST criteria
Periodo de tiempo: Up to 3 years
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Up to 3 years
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: John Murren, Yale University
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-2013-00044
- HIC #12760
- R21CA097750 (Subvención/contrato del NIH de EE. UU.)
- CDR0000322889 (Identificador de registro: PDQ (Physician Data Query))
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. .
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