E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced or Metastatic ER+/HER2- Breast Cancer |
Cáncer de mama avanzado o metastásico ER+/HER2- |
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E.1.1.1 | Medical condition in easily understood language |
Breast cancer that has spread beyond the breast tissue and surrounding lymph nodes and tests positive for estrogen receptors and negative for human epidermal growth factor receptor-2 |
Cáncer de mama que se ha extendido más alla del tejido de la mama y gáglios linfáticos circundantes y resultado positivo en test para receptores de estrógenos y negativo Her2. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10070575 |
E.1.2 | Term | Estrogen receptor positive breast cancer |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
? To evaluate the efficacy of GDC-0810 compared with fulvestrant in the intent to treat (ITT) population as measured by progression free survival (PFS) ? To evaluate the efficacy of GDC-0810 compared with fulvestrant in the estrogen receptor 1 (ESR1) mutant population as measured by PFS |
- Evaluar la eficacia de GDC-0810 en comparación con fulvestrant en la población con intención de tratar (IDT) medida según la supervivencia sin progresión (SSP). - Evaluar la eficacia de GDC-0810 en comparación con fulvestrant en la población con mutaciones detectables en el ESR1 medida según la SSP |
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E.2.2 | Secondary objectives of the trial |
? To assess the clinical activity of GDC-0810 versus fulvestrant, as measured by objective response rate (ORR), duration of response (DOR), clinical benefit rate (CBR), and overall survival (OS) ? To evaluate the safety and tolerability of GDC-0810 compared with fulvestrant, focusing on the nature, frequency, and severity of serious and non-serious adverse events ? To assess the pharmacokinetics of GDC-0810 in patients with advanced or metastatic breast cancer (MBC) resistant to aromatase inhibitor (AI) therapy |
- Evaluar la actividad clínica de GDC-0810 frente a fulvestrant, medida según la tasa de respuesta objetiva (TRO), la duración de la respuesta objetiva (DRO), la tasa de beneficio clínico (TBC) y la supervivencia global (SG). - Evaluar la seguridad y la tolerabilidad de GDC-0810 en comparación con fulvestrant, con especial atención en la naturaleza, la frecuencia y la gravedad de los acontecimientos adversos graves y no graves. - Evaluar la farmacocinética de GDC-0810 en pacientes con cáncer de mama avanzado o metastásico resistente al tratamiento con inhibidor de la aromatasa (IA). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Postmenopausal women with histologically or cytologically confirmed invasive, estrogen receptor positive (ER+)/ human epidermal growth factor receptor 2 negative (HER2-) (defined by local guidelines) metastatic or inoperable (not amenable to resection or other local therapy with curative intent), locally advanced breast cancer - Patients for whom endocrine therapy (e.g., fulvestrant) is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study, as per national or local treatment guidelines - Radiologic/objective evidence of recurrence or progression to the most recent systemic therapy for breast cancer - Radiologic/objective evidence of breast cancer recurrence or progression while on or within 6 months after the end of adjuvant treatment with an AI, or progression while on or within 1 month after the end of prior AI treatment for locally advanced or MBC - Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or non-measurable, evaluable disease with at least one evaluable bone lesion by RECIST v1.1 based on radiologic scans within 28 days of Day 1 of Cycle 1 - Eastern Cooperative Oncology Group Performance Status of 0 or 1 - Adequate hematologic and end-organ function |
- Mujeres posmenopáusicas con cáncer de mama ER + /HER2- (definido según las directrices locales) metastásico o irresecable (no se puede extirpar ni intentar curar con cualquier otro tratamiento local), invasivo o localmente avanzado y diagnosticado de forma citológica o histológica. - Pacientes a las que se recomienda el tratamiento endrocrino (p. ej., fulvestrant) y para las que no está indicado el tratamiento con quimioterapia citotóxica en el momento del acceso al estudio, según las directrices del tratamiento locales y nacionales. - Pruebas objetivas/radiológicas de recurrencia o progresión hasta el tratamiento generalizado más reciente para el cáncer de mama. - Pruebas objetivas/radiológicas de recurrencia o progresión del cáncer de mama durante el tratamiento complementario con un IA o en un período posterior de 6 meses tras la finalización de este, o bien progresión durante el tratamiento con IA anterior para cáncer de mama localmente avanzado o metastásico o en un período posterior de 1 mes tras la finalización de este. - Las pacientes deben tener una enfermedad mensurable según el sistema RECIST versión 1.1 o inmensurable, enfermedad evaluable con al menos una lesión ósea evaluable según RECIST versión 1.1 en función de las exploraciones radiológicas realizadas en el plazo de 28 días del día 1 del ciclo 1. - Niveles de calidad de vida de 0 o 1 de ECOG - Actividad suficiente hematológica y del órgano terminal |
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E.4 | Principal exclusion criteria |
- HER2 positive disease (immunohistochemistry [IHC] 3+ staining, fluorescence in situ hybridization [FISH] positive, and/or chromogenic in situ hybridization [CISH] positive) - Prior treatment with fulvestrant - Prior anti-cancer therapy within 2 weeks prior to Cycle 1 Day 1 - Prior radiation therapy within 2 weeks prior to Cycle 1 Day 1 - Prior treatment with >1 cytotoxic chemotherapy regimens or >2 endocrine therapies for advanced or metastatic disease - Ongoing, acute treatment-related toxicity that has not resolved to Grade <=1 or been deemed stable by the investigator - Concurrent hormone replacement therapy - Known untreated or active central nervous system metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control) - History of other malignancy within the previous 5 years - Inability or unwillingness to swallow pills or receive intramuscular injections - Clinically significant cardiac or pulmonary dysfunction - Major surgical procedure or significant traumatic injury within 28 days prior to Day 1 of Cycle 1 or anticipation of the need for major surgery during the course of study treatment |
- Cáncer HER2 positivo (tinción inmunohistoquímica con 3 +, hibridación fluorescente in situ [FISH] positiva, o hibridación cromogénica in situ [CISH] positiva). - Tratamiento previo con fulvestrant. - Tratamiento oncológico previo en el plazo de dos semanas antes del día 1 del ciclo 1. - Radioterapia previa en el periodo de dos semanas antes del día 1 del ciclo 1. - Tratamiento previo con > 1 tratamiento de quimioterapia citotóxica o > 2 tratamientos endocrinos para cáncer metastásico o avanzado. - Toxicidad aguda y continua relacionada con el tratamiento que no se ha resuelto hasta el grado <= 1 o se ha considerado estable por parte del investigador. - Hormonoterapia restitutiva simultánea. - Metástasis conocidas del sistema nervioso central (SNC) activa o sin tratar (que progresan o requieren anticonvulsivos o corticoesteroides para el control sintomático); - Antecedentes de otros tumores malignos en los 5 años anteriores. - Incapacidad o negativa a tragar pastillas o recibir inyecciones i. m. - Disfunción pulmonar o cardíaca clínicamente significativa - Procedimiento quirúrgico importante o traumatismo significativo en un plazo de 28 días anteriores al día 1 del ciclo 1 o previsión de un procedimiento quirúrgico importante durante el ciclo del tratamiento en estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
PFS as determined by the investigator per RECIST v1.1 |
SSP determinada por parte del investigador según el sistema RECIST versión 1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. OS 2. ORR (partial response [PR] plus complete response [CR]) as determined by the investigator per RECIST v1.1 3. DOR as determined by the investigator per RECIST v1.1 4. CBR 5. Incidence of adverse events and serious adverse events 6. Clinically significant changes in vital signs, physical findings, and clinical laboratory results 7. Apparent clearance, volume of distribution, absorption rate constant of GDC-0810 |
1.SG 2. TRO (Remisión parcial (RP) más remisión completa (RC) determinda por parte del investigador según sistema RECIST 1.1. 3. DRO determinada por parte del investigador según el sistema RECIST versión 1.1. 4. TBC 5. Incidencia de aconteciminetos adversos y acontecimientos adversos graves. 6. Cambios clínicamente significativos de las constantes vitales, los datos obtenidos en la exploración física y los resultados clínicos del laboratorio. 7. Aclaramiento evidente, el volumen de distribución, la constante de la tasa de absorción de GDC-0810 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-6. 26 months 7. Predose and 3 hours postdose at Cycle 1 Day 1 and Cycle 3 Day 1 |
1-6. 26 meses. 7. Pre dosis y 3 horas post dosis en Ciclo 1 Día 1 y Ciclo 3 Día 1. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Germany |
Korea, Republic of |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of this study is defined as the date when the last patient, last visit (LPLV) occurs or the date at which the last data point required for statistical analysis (i.e., progression-free survival) or safety follow-up is received from the last patient, whichever occurs later, or when the Sponsor decides to stop the study. |
La finalización del estudio se define como la fecha en la que se produce la última visita, de la última paciente o la fecha en la que se recibe el último punto de datos necesario para el análisis estadístico (es decir, SSP) o el seguimiento de la seguridad de la última paciente, lo que ocurra más tarde, o cuando el promotor decide detener el estudio. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |