Molecular Imaging of Fulvestrant Effects on Availability of ER Binding Sites
In Vivo Imaging of the Effect of Fulvestrant on the Availability of Estrogen Receptor Binding Sites in Metastatic Breast Tumor Lesions Using FES-PET
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
The estrogen receptor (ER) is expressed in approximately 70% of the breast carcinomas. In these patients signaling via the ER induces proliferation and cell survival of malignant cells. Fulvestrant can inhibit this signaling route by blocking the receptor and decreasing ER-expression by increasing its turn-over rate.
The historical standard dose of fulvestrant was 250mg every 28 days i.m.; however studies performing serial biopsies showed that ER-downregulation was suboptimal. Recently the standard dose has been set to 500mg i.m. on day 1; 14; 28 and every 28 days thereafter. Although slightly more effective than the 250mg dose, still questions remain with respect to the required dose to establish maximal downregulation of ER-signaling.
Immunohistochemistry only provides static information, i.e. the level of ER-expression. However, dynamic information evaluating the effects of fulvestrant on occupancy of ERs, may also be valuable.
Whole-body imaging of the availability of ER binding sites using FES-PET may prove valuable to evaluate the effects of fulvestrant on the ER non-invasively in individual patients. This potentially allows adjustment of dosing in individual patients to aid therapy efficacy.
In this pilot-study we will evaluate 15 metastatic breast cancer patients. All patients will undergo FES-PET/CT at baseline, FES-PET after 1 month, and FES-PET/CT after three months. Hormone- and fulvestrant levels will be measured in all patients. Whenever possible, tumor biopsies will be performed to correlate to FES-PET results.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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Groningen, Países Bajos, 9713GZ
- University Medical Center Groningen
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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:
- 1. Patients with a history of histological proven ER-positive primary breast cancer and, whenever available, histological proven ER-positive recurrence. 2. Post-menopausal status (age ≥ 45 years with amenorrhea for > 12 months or prior bilateral ovariectomy 3. Documentation of a negative pregnancy test must be available for women less than 2 years after menopause 4. Progressive disease after 2 lines of hormonal therapy 5. No previous fulvestrant treatment 6. ER-antagonists should be discontinued for 5 weeks prior to FES-PET to prevent false negative FES-PET results. The use of aromatase inhibitors is allowed 7. ECOG performance status 0, 1 or 2 8. Life expectancy > 3 months 9. Creatinine clearance ≥ 30 ml/min 10. Age ≥ 18 years 11. Signed written informed consent 12. Able to comply with the protocol
Exclusion Criteria:
- 1. Evidence of central nervous system metastases 2. Presence of life-threatening visceral metastases 3. > 3 lines of endocrine therapy for metastatic disease 4. > 2 lines of chemotherapy in metastatic disease
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Diagnóstico
- 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: Single arm
Fluoroestradiol-PET is performed at baseline, after 1 month, and 3 months
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A FES-PET/(CT) will be performed thrice during protocol execution.
Patients will be injected with ~200MBq 18F-FES
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Visualize and quantify changes in FES uptake in tumor lesions during fulvestrant 500mg therapy
Periodo de tiempo: baseline; 1 month; 3 months
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FES-uptake will be calculated for all tumor lesions at baseline, 1 month and 3 months. Changes between FES-uptake during fulvestrant therapy will be calculated for:
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baseline; 1 month; 3 months
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To evaluate the proportion of patients with an incomplete down-regulation/occupancy of ERs as determined by FES-PET
Periodo de tiempo: baseline, 1 month and 3 months
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FES-uptake will be calculated for all tumor lesions at baseline, after 1 month and after 3 months. Incomplete down-regulation/ occupancy of ERs is defined as 1) an absolute SUV> 1.5, and 2) a relative decrease in SUV of <75% during fulvestrant therapy. The proportion of patients that match these criteria will be given for:
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baseline, 1 month and 3 months
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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The feasibility to quantify changes in FES-uptake in liver metastases
Periodo de tiempo: baseline, 1 month and 3 months
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Liver metastases detected on PET/CT will be serially quantified at the 3 different time points to evaluate the feasibility to quantify liver lesions on FES-PET/CT
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baseline, 1 month and 3 months
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to correlate FES-PET results to patient and tumor response on fulvestrant therapy
Periodo de tiempo: baseline, 1 month, 3 months
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Patients will be categorized as responders and non-responders by standard follow-up (monthly visits, 3-monthly CT, other techniques when indicated). The predictive value of FES-PET for response to fulvestrant will be calculated for:
Lesion-based evaluation will be performed for measurable lesions as defined by RECIST criteria, and changes in diameter will be correlated to changes in FES-uptake at:
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baseline, 1 month, 3 months
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Explorative analysis to correlate several factors (among which tumor burden, ER-expression, fulvestrant levels, estradiol levels, patient weight) to FES uptake will be performed.
Periodo de tiempo: baseline, 1 month and 3 months
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Explorative analysis to correlate several factors at different timepoints (baseline, 1 month, 3 months) to FES uptake.
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baseline, 1 month and 3 months
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Colaboradores e Investigadores
Patrocinador
Publicaciones y enlaces útiles
Publicaciones Generales
- Mortimer JE, Dehdashti F, Siegel BA, Trinkaus K, Katzenellenbogen JA, Welch MJ. Metabolic flare: indicator of hormone responsiveness in advanced breast cancer. J Clin Oncol. 2001 Jun 1;19(11):2797-803. doi: 10.1200/JCO.2001.19.11.2797.
- Linden HM, Stekhova SA, Link JM, Gralow JR, Livingston RB, Ellis GK, Petra PH, Peterson LM, Schubert EK, Dunnwald LK, Krohn KA, Mankoff DA. Quantitative fluoroestradiol positron emission tomography imaging predicts response to endocrine treatment in breast cancer. J Clin Oncol. 2006 Jun 20;24(18):2793-9. doi: 10.1200/JCO.2005.04.3810. Epub 2006 May 8.
- Howell A, Bergh J. Insights into the place of fulvestrant for the treatment of advanced endocrine responsive breast cancer. J Clin Oncol. 2010 Oct 20;28(30):4548-50. doi: 10.1200/JCO.2010.30.6266. Epub 2010 Sep 20. No abstract available.
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 (Estimar)
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
- Efectos fisiológicos de las drogas
- Hormonas
- Hormonas, sustitutos hormonales y antagonistas hormonales
- Estrógenos
- Agentes Anticonceptivos Hormonales
- Agentes anticonceptivos
- Agentes de control reproductivo
- Agentes anticonceptivos femeninos
- Estradiol
- Estradiol 17 beta-cipionato
- 3-benzoato de estradiol
- Fosfato de poliestradiol
Otros números de identificación del estudio
- RUG2010-2611
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