- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00380029
Erlotinib Before and After Surgery in Treating Patients With Muscle-Invasive Bladder Cancer
A Phase II Study of Erlotinib (Tarceva®) in Patients With Muscle-Invasive Bladder Cancer Undergoing Radical Cystectomy
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving erlotinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving erlotinib after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This phase II trial is studying how well erlotinib works when given before and after surgery in treating patients with muscle-invasive bladder cancer.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
OBJECTIVES:
Primary
- Determine the effect of neoadjuvant erlotinib hydrochloride on histopathological, molecular, and genetic correlates in patients undergoing radical cystectomy for muscle-invasive bladder cancer.
Secondary
- Determine the pathological complete response rate in surgical specimens from patients treated with this drug.
- Determine recurrence and progression rates after cystectomy (up to 2 years after surgery) in patients treated with neoadjuvant and adjuvant erlotinib hydrochloride.
- Determine 2- and 5-year disease-free, disease-specific, and overall survival rates in patients treated with this drug.
- Determine the safety of this drug in these patients.
OUTLINE: This is an open-label study.
Patients receive oral erlotinib hydrochloride once daily for 4 weeks. Patients then undergo radical cystectomy with curative intent. Within 12 weeks after surgery, patients resume oral erlotinib hydrochloride* once daily for up to 2 years in the absence of disease progression or unacceptable toxicity.
Note: *Patients who are candidates for adjuvant chemotherapy (e.g., found to have pathologic stage T3 (pT3), Node positive (N+) disease) do not receive erlotinib hydrochloride after surgery.
Tumor tissue is obtained at baseline (at the original or confirmatory transurethral resection of the bladder tumor) and at the time of cystectomy for analysis of drug-specific and tissue-based biomarkers by western blot, immunohistochemistry, and gene array techniques. Histopathological, molecular, and genetic correlates are analyzed to better understand the potential effects of the epidermal growth factor receptor (EGFR) inhibition in transitional cell carcinoma and to determine the effect of neoadjuvant erlotinib on gene expression. Tumor tissue is also evaluated by real-time polymerase chain reaction to confirm drug effects on expected targets and on EGFR expression, activity, and affected signaling pathways in the disease state and by microarray analysis to define expression phenotypes correlating with outcome, distinguish responders from nonresponders, and determine effects of drug treatment on gene expression in disease.
Patients are followed periodically for up to 5 years after surgery.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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North Carolina
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Chapel Hill, North Carolina, Estados Unidos, 27599-7295
- Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
DISEASE CHARACTERISTICS:
Histologically confirmed muscle-invasive bladder cancer, meeting the following criteria:
- Clinical stage T2 disease
- No locally-extensive clinical stage T3 or T4 disease
- No metastatic disease (N+, M+) by physical exam or radiologic evaluation
- Must have undergone prior initial or confirmatory transurethral resection of the bladder tumor (TURBT)
- Candidate for and has agreed to undergo radical cystectomy with curative intent
- No non-transitional cell carcinoma histologies
PATIENT CHARACTERISTICS:
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Granulocyte count > 1,500/mm³
- Platelet count > 100,000/mm³
- Bilirubin normal
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 times upper limit of normal
- Creatinine normal
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No contraindication to erlotinib hydrochloride or other tyrosine kinase inhibitors
PRIOR CONCURRENT THERAPY:
No prior radiotherapy or systemic chemotherapy for bladder cancer
- Prior single-dose mitomycin C allowed at the time of TURBT
- Prior 6- or 12-week course of adjuvant intravesical Bacillus Calmette-Guerin (BCG) therapy with or without recombinant interferon alfa-2a allowed
- At least 4 weeks since other prior or concurrent radiotherapy, chemotherapy, or hormonal therapy
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: Erlotinib
erlotinib given before and after transurethral resection of a bladder tumor, TURBT
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Erlotinib will be given at a dose of 150 mg per day for 4 weeks before undergoing planned radical cystectomy.
In addition, patients will continue on erlotinib daily at a dose of 150 mg per day (qd dosing) for up to 2 years after surgery (beginning within 12 weeks of surgery) or until evidence of disease recurrence or progression
Otros nombres:
Will occur 4 weeks prior to dosing with erlotinib
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
EGFR Activation Signal (AKT2) Expression to Predict Sensitivity to Erlotinib
Periodo de tiempo: 4 weeks before treatment and 4 weeks post treatment
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Determine the effect of neoadjuvant erlotinib hydrochloride on histopathological, molecular, and genetic correlates in patients undergoing radical cystectomy for muscle-invasive bladder cancer.
Gene expression of pre-treatment and post-treatment tumor samples were analyzed to define molecular determinants of response or resistance to epidermal growth factor receptor (EGFR) inhibition.
Both in vitro and in vivo EGFR-associated signatures were evaluated on pre-treatment bladder tumors.
Candidate molecular determinants of sensitivity to EGFR inhibition were characterized and examined for their ability to predict sensitivity to EGFR inhibitors in vitro.
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4 weeks before treatment and 4 weeks post treatment
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Pathological Complete Response Rate
Periodo de tiempo: 4 weeks
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Determine the pathological complete response rate (P0 rate) after undergoing radical cystectomy (RC).
Evaluated using Response Evaluation Criteria In Solid Tumors (RECIST).
Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
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4 weeks
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Disease Recurrence and Progression Rates After Cystectomy
Periodo de tiempo: 2 years
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To determine disease recurrence/progression rates after cystectomy in patients treated with erlotinib
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2 years
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Overall Survival Rate
Periodo de tiempo: 25 months
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The number of patients who remained alive and with no evidence of disease at the mean (range) follow-up of 24.8 months (3.0-36.6).
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25 months
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Number of Subjects Experiencing Adverse Events
Periodo de tiempo: 4 weeks - 2 years following surgery
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The incidence of all toxicities observed during neoadjuvant and adjuvant treatment phase.Toxicity will be graded per the Common Terminology Criteria for Adverse Events (CTCAE) 2.0.
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4 weeks - 2 years following surgery
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Raj S. Pruthi, MD, UNC Lineberger Comprehensive Cancer Center
Publicaciones y enlaces útiles
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
Términos MeSH relevantes adicionales
- Neoplasias
- Neoplasias Urológicas
- Neoplasias urogenitales
- Neoplasias por sitio
- Enfermedades urológicas
- Enfermedades de la vejiga urinaria
- Neoplasias de la vejiga urinaria
- Mecanismos moleculares de acción farmacológica
- Inhibidores de enzimas
- Agentes antineoplásicos
- Inhibidores de la proteína quinasa
- Clorhidrato de erlotinib
Otros números de identificación del estudio
- LCCC 0521
- P30CA016086 (Subvención/contrato del NIH de EE. UU.)
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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Ensayos clínicos sobre Erlotinib
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University of ChicagoNational Cancer Institute (NCI)TerminadoMesotelioma Peritoneal MalignoEstados Unidos
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Tragara Pharmaceuticals, Inc.TerminadoCáncer de pulmón de células no pequeñas recidivanteEstados Unidos
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PfizerTerminadoCáncer de pulmón de células no pequeñasEstados Unidos, Corea, república de, Reino Unido, Grecia, Eslovaquia, Francia, Bélgica, Irlanda, Japón, España, Porcelana, Suecia, India, Hungría, Suiza, Federación Rusa, Alemania, México, Dinamarca, Austria, Finlandia, Polonia, Sudáfrica