Trastuzumab and Erlotinib as First-Line Therapy in Treating Women With Metastatic Breast Cancer Associated With HER2/Neu Overexpression
Phase I/II Study Of Herceptin Combined With OSI-774 In The First-Line Treatment Of Metastatic Breast Cancer Associated With HER2/Neu Overexpression
RATIONALE: Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Biological therapies such as erlotinib may interfere with the growth of tumor cells and slow the growth of the tumor. Combining trastuzumab with erlotinib may kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of combining trastuzumab with erlotinib as first-line therapy in treating women who have metastatic breast cancer associated with HER2/neu overexpression.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
OBJECTIVES:
- Determine the maximum tolerated dose and recommended phase II dose of erlotinib when combined with trastuzumab (Herceptin) as first-line therapy in women with metastatic breast cancer associated with HER2/neu overexpression. (Phase I closed to accrual as of 01/2004)
- Determine the safety profile of this regimen in these patients.
- Determine the rate and duration of objective response in patients treated with this regimen.
- Determine the pharmacologic behavior of this regimen in these patients.
- Determine time to disease progression and duration of survival in patients treated with this regimen.
- Correlate the antitumor activity of this regimen with epidermal growth factor receptor expression in these patients.
OUTLINE: This is a dose-escalation study of erlotinib. (Phase I closed to accrual as of 01/2004).
Patients receive oral erlotinib once daily beginning on day 2 and trastuzumab (Herceptin) IV over 30-90 minutes (1-4 hours after erlotinib) once weekly beginning on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are treated at the recommended phase II dose.
Patients are followed every 2 months.
PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for the phase I portion (closed to accrual as of 01/2004) and 27-81 patients will be accrued for the phase II portion of this study.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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California
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Los Angeles, California, Estados Unidos, 90095-1781
- Jonsson Comprehensive Cancer Center at UCLA
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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:
- Women aged > 18 years
- Histologically documents metastatic breast cancer
- HER2 positive using Fluorescence In Situ Hybridization (FISH)
- For phase I, patients who have previously received treatment for their metastatic disease are allowed to participate.
- For the phase II portion of the study, patients must have measureable disease (> 2 cm; > 1 cm on spiral CT scan)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- A life expectancy of > 3 months
- Use of effective means of contraception
Exclusion Criteria:
- For Phase II, prior cytotoxic chemotherapy and/or prior Herceptin for their metastatic disease. Prior treatment in the adjuvant setting is allowed.
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
please see intervention description
|
Day 1 4mg/kg IV 2 mg/kg IV weekly.
Otros nombres:
100 mg daily on Course 1 Day 2. After three weeks patients who have not experienced specific adverse events, dose will be escalated to 150 mg daily.
Patients who have experienced specific adverse events dose will remain 100 mg daily or dose reduced as necessary per protocol.
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
The Objective Response Rate as Defined as Stable Disease or the Rate of Complete and Partial Responses Determined on Two Consecutive Occasions Greater Than or Equal to 4 Weeks Apart.
Periodo de tiempo: 5 years
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Complete Response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. Also called complete remission. Partial Response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. Also called partial remission. |
5 years
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Recommended Dose for Phase II
Periodo de tiempo: treatment period
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treatment period
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Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
|---|---|
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Duration of Objective Response
Periodo de tiempo: 5 years
|
5 years
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Incidence of Adverse Events
Periodo de tiempo: 5 years
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5 years
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Serum Concentration of Herceptin at Specified Time-points.
Periodo de tiempo: 4 months
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4 months
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Colaboradores e Investigadores
Patrocinador
Colaboradores
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 (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades de la piel
- Neoplasias
- Neoplasias por sitio
- Enfermedades de los senos
- Neoplasias de mama
- Mecanismos moleculares de acción farmacológica
- Inhibidores de enzimas
- Agentes antineoplásicos
- Agentes antineoplásicos inmunológicos
- Inhibidores de la proteína quinasa
- Trastuzumab
- Clorhidrato de erlotinib
Otros números de identificación del estudio
- 01-06-020
- CDR0000069295
- GENENTECH-OSI2365s
- NCI-G02-2057
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