- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00526591
Everolimus in Treating Patients With Newly Diagnosed Localized Prostate Cancer
Randomized Phase II Study of Two Different Doses of RAD-001 (Everolimus) as Neo-Adjuvant Therapy in Patients With Localized Prostate Cancer
RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving everolimus before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PURPOSE: This randomized phase II trial is studying the side effects and how well everolimus works in treating patients with newly diagnosed localized prostate cancer.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
OBJECTIVES:
Primary
- To determine the clinical effects of everolimus, in terms of pathologic response (i.e., histologic P0, margin status, or capsular penetration) and surgical outcome, in patients with newly diagnosed localized prostate cancer treated with two different doses of everolimus prior to radical prostatectomy.
- To evaluate the safety and tolerability of this drug in these patients.
Secondary
- To determine the effect of this drug on prostate-specific antigen (PSA) levels in these patients.
- To determine the effect of this drug on levels of expression of PTEN, Akt, phospho-mTOR (i.e., Se2448), phospho-p70 S6 kinase (i.e., Thre389), phospho-Smad3 (i.e., Ser433/435), phospho-Smads 1/5 (i.e., Ser463/465), AR, and TUNEL in these patients.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive low-dose oral everolimus once daily for up to 8 weeks in the absence of unacceptable toxicity.
- Arm II: Patients receive high-dose oral everolimus once daily for up to 8 weeks in the absence of unacceptable toxicity.
Within 7 days after the last dose of everolimus, all patients undergo radical prostatectomy with bilateral pelvic lymphadenectomy.
Tumor biopsy specimens acquired prior to treatment and prostate tumor tissue acquired at the time of radical prostatectomy are evaluated for biomarker correlative studies. Tissue samples are assessed by immunohistochemistry (IHC) and tissue microarray analysis for expression of cellular and molecular biomarkers (i.e., p-S6, p-4E-BP1, and p-Akt) that correlate with response. Prostatectomy specimens are also assessed by pathologic analysis for histopathologic response (i.e., pathologic stage, Gleason score, margin status, and tumor size).
After completion of study therapy, patients are followed at 6 weeks.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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Ohio
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Cleveland, Ohio, Estados Unidos, 44195
- Cleveland Clinic Taussig Cancer institute, Case Comprehensive 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
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed newly diagnosed, localized adenocarcinoma of the prostate, meeting any of the following criteria:
- Clinical stage T2a, T2b, T2c, or T3 disease (any grade or PSA)
- Gleason score 7 (4+3 only) or ≥ 8 (any stage or PSA)
- Serum PSA ≥ 10 ng/dL (any grade or stage)
- Any stage, PSA, or Gleason score AND ≥ 35% chance of biochemical failure at 5 years based on Kattan's nomogram
- Recommended for radical prostatectomy
- Normal testosterone level
- No pure neuroendocrine or small cell prostate cancer
- No metastatic disease by CT scan, MRI, bone scan, or X-ray
- No clinical evidence of CNS metastases
PATIENT CHARACTERISTICS:
Inclusion criteria:
- ECOG performance status (PS) 0-1 or Karnofsky PS 70-100%
- ANC ≥ 1,500/μL
- Platelet count ≥ 100,000/μL
- Hemoglobin ≥ 8 g/dL
- AST and ALT ≤ 1.5 times upper limit of normal (ULN)
- Bilirubin ≤ 1.5 times ULN
- Creatinine ≤ 1.5 times ULN
- PT/PTT normal (no anticoagulants)
- No active unresolved infection
- No known HIV positivity
- Fertile patients must use effective contraception during and for 6 months after completion of study therapy
Exclusion criteria:
- Known hypersensitivity to everolimus or other rapamycins (e.g., sirolimus or temsirolimus) or to its excipients
Gastrointestinal (GI) disease, condition, or symptoms that may significantly impair GI function and alter the absorption of everolimus, including any of the following:
- Ulcerative disease
- Uncontrolled nausea
- Vomiting
- Diarrhea
- Malabsorption syndrome
- Other active malignancy or malignancy at ≥ 30% risk for relapse after completion of therapy, except nonmelanoma skin cancer
Uncontrolled concurrent illness including, but not limited to, any of the following:
- Ongoing or active infection (e.g., bacterial, viral or fungal)
- Severely impaired lung function
- Uncontrolled diabetes (fasting serum glucose > 1.5 times ULN)
- Liver disease (e.g., cirrhosis, chronic active hepatitis, or chronic persistent hepatitis)
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situation that would limit study compliance
- Any underlying medical condition which, in the principal investigator's opinion, will make the administration of everolimus hazardous OR obscure the interpretation of adverse events
PRIOR CONCURRENT THERAPY:
- More than 4 weeks since major surgery
- More than 3 months since finasteride
- No prior or concurrent radiotherapy to the prostate gland or pelvis
- No prior hormones (e.g., luteinizing hormone-releasing hormone [LHRH] agonists, LHRH antagonists, or antiandrogens [e.g., bicalutamide, flutamide, or nilutamide]) and/or PC-SPES (or PC-x product) or estrogen-containing nutraceuticals
- No prior rapamycin mTOR inhibitor
- No prior small bowel resection that may significantly impair GI function and alter the absorption of everolimus
- No prior or concurrent immunotherapy, chemotherapy, or other investigational therapy for prostate cancer
- No other concurrent investigational or commercial agents
- No other concurrent anticancer agents
- No concurrent, chronic treatment with systemic steroids (except inhaled or topical steroids) or another immunosuppressive agent
- No concurrent live vaccines
- No concurrent strong inhibitors or inducers of the isoenzyme CYP3A administered as systemic therapy
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Low-dose Everolimus Cohort
5mg Everolimus daily continuously for 8 weeks and conventional surgery
|
Patients will receive arm-specific dosage of Everolimus daily continuously for 8 week
Otros nombres:
Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).
|
|
Comparador activo: High-dose Everolimus Cohort
10mg Everolimus daily continuously for 8 weeks and conventional surgery
|
Patients will receive arm-specific dosage of Everolimus daily continuously for 8 week
Otros nombres:
Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Proportion of Patients Who Are P0 (i.e., no Clinically Detectable Tumor in the Pathologic Specimen) at Surgery
Periodo de tiempo: After 8 weeks of therapy at the time of prostatectomy
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Specimens are fixed in formalin for 24 hours.Specimens are the cut at 3 mm intervals perpendicular to the rectal surface and the sections are examined grossly and microscopically on routine Hematoxylin and Eosin stain (H&E) (pathologic complete response or P0) will be defined as responders.
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After 8 weeks of therapy at the time of prostatectomy
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Toxicity Profile of Each Dose (Number of Patients With Worst Grade Toxicity)
Periodo de tiempo: at daily dose for 8 weeks
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Toxicity will be assessed using the NIH-NCI Common Terminology Criteria for Adverse Events, version 3.0 (CTCAEv3.0)
|
at daily dose for 8 weeks
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Change in PSA
Periodo de tiempo: Up to 16 weeks after start of study
|
Time-to-event data, such as change in PSA will be summarized using the method of Kaplan and Meier.
|
Up to 16 weeks after start of study
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Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Effect of Treatment on Biological and Molecular Markers
Periodo de tiempo: After 8 weeks of therapy
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Immunohistochemical Staining of Cellular and Molecular Markers in Prostate Tumor Tissue
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After 8 weeks of therapy
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Jorge A. Garcia, MD, Case Comprehensive Cancer Center
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
Otros números de identificación del estudio
- CASE21806
- P30CA043703 (Subvención/contrato del NIH de EE. UU.)
- CASE-21806 (Otro identificador: Case Comprehensive Cancer Center)
- CASE-21806-CC256 (Otro identificador: Cancer Center IRB)
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los 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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