E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Breast Cancer |
cancer de mama metastásico |
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E.1.1.1 | Medical condition in easily understood language |
Metastatic Breast Cancer |
cancer de mama metastásico |
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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 | 15.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic 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 (as measured by progression-free survival [PFS]) of paclitaxel + GDC-0941 versus paclitaxel + placebo in patients with and without PIK3CA mutations and in all treated patients |
Evaluar la eficacia (medida como supervivencia libre de progresión [PFS]) de paclitaxel + GDC-0941 versus paclitaxel + placebo en pacientes con y sin mutaciones PIK3CA y en todos los pacientes tratados |
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E.2.2 | Secondary objectives of the trial |
?To evaluate the safety of paclitaxel + GDC-0941 versus paclitaxel + placebo ?To assess the clinical activity, as measured by response rate and duration of response, of paclitaxel + GDC-0941 versus paclitaxel + placebo in patients with and without PIK3CA mutations and in all treated patients ?To assess the prognostic and predictive effects of PIK3CA mutations on PFS ?To assess the population pharmacokinetics of GDC-0941 and paclitaxel when co-administered |
-Evaluar la seguridad de paclitaxel + GDC-0941 frente a paclitaxel + placebo. -Evaluar la actividad clínica, determinada mediante la tasa de respuesta y la duración de la respuesta, de paclitaxel + GDC-0941 frente a paclitaxel + placebo en pacientes con y sin mutaciones de PIK3CA y en todas las pacientes tratadas. -Evaluar los efectos pronósticos y predictivos de las mutaciones de PIK3CA sobre la SSP. - Evaluar la farmacocinética poblacional de GDC-0941 cuando se administra con paclitaxel y GDC- 0941 cuando se administran en combinación. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
? Age > 18 ? Women with histologically or cytologically confirmed adenocarcinoma of the breast, with measurable or non measurable locally recurrent or metastatic disease ?Human epidermal growth factor receptor 2 (HER2) |
- Edad igual o superior a los 18 años. - Mujeres con Adenocarcinoma de mama histológica o citológicamente confirmado, con enfermedad localmente recurrente o metastásica cuantificable o no cuantificable. - Receptor 2 del factor de crecimiento epidérmico humano (HER2) |
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E.4 | Principal exclusion criteria |
?Prior non-capecitabine chemotherapy for locally recurrent or metastatic disease ?For patients who have received - prior treatment with capecitabine in the metastatic setting, treatment must have been completed < 2 weeks prior to Cycle 1, Day 1.Prior treatment with a PI3K inhibitor for advanced breast cancer or MBC (including but not limited to GDC 0941, GDC 0980, BEZ235, BKM120, BYL719, LY294002, PIK-75, TGX-221, XL147, XL765, SF1126, PX-866, D 87503, D-106669, GSK615, CAL101) Prior mTOR inhibitors (e.g., everolimus) are permitted provided treatment concluded at least 2 weeks prior to Cycle 1, Day 1. ?History of intolerance to a taxane-containing therapy ?History of clinically significant cardiac or pulmonary dysfunction ?History of malabsorption syndrome or other condition that would interfere with enteral absorption ?Clinically significant history of liver disease ?Active autoimmune disease or active inflammatory disease ?Immunocompromised status ?Need for current chronic corticosteroid therapy ?Pregnancy, lactation, or breastfeeding ?Current severe, uncontrolled systemic disease ?Known untreated or active central nervous system (CNS) metastases |
- Quimioterapia previa sin capecitabina para una enfermedad localmente recurrente o metastásica. - En el caso de pacientes que hayan recibido tratamiento previo con capecitabina en el contexto metastásico, el tratamiento deberá haberse completado con más de 2 semanas de antelación al día 1 del ciclo 1. Tratamiento previo con un inhibidor de PI3K para el cáncer de mama avanzado o CMM (incluyendo, entre otros, GDC-0941, GDC-0980, BEZ235, BKM120, BYL719, LY294002, PIK-75, TGX-221, XL147, XL765, SF1126, PX-866, D-87503, D-106669, GSK615 y CAL101). Se permite el tratamiento previo con inhibidores de mTOR (p. ej., everolimús) siempre que el tratamiento haya concluido al menos 2 semanas antes del día 1 del ciclo 1. - Historial de intolerancia a terapia con taxanos - Disfunción cardíaca o pulmonar clínicamente significativa - Antecedentes de síndrome de malabsorción u otra enfermedad que pudiera interferir en la absorción enteral. - Historia clínica significativa de enfermedad hepática - enfermedad autoinmune activa o enfermedad inflamatoria activa - Estado inmunodeprimido -Necesidad de tratamiento crónico con corticoesteroides -Embarazo o lactancia - Enfermedad sistémica no controlada grave -Metástasis conocidas del sistema nervioso central |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) in patients with and without PIK3CA tumor mutations, as well as in all treated patients as assessed by the investigator per modified RECIST version 1.1 |
supervivencia libre de progresión [PFS] en pacientes con y sin mutaciones PIK3CA, así como en todos los pacientes tratados y evaluados por el investigador segun la version modificada RECIST v1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Every 12 weeks |
Cada 12 semanas |
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E.5.2 | Secondary end point(s) |
The secondary outcome measures in all treated patients and in patients with and without PIK3CA mutations are: ?Objective tumor response as assessed by investigator per modified RECIST v1.1 ?Clinical benefit, defined as partial response (PR), complete response (CR), or stable disease (SD), lasting for at least 6 months (i.e., 26 weeks) |
Los criterios secundarios medido en todos los pacientes tratados y en pacientes con y sin mutaciones PIK3CA son: ?respuesta objetiva del tumor valorada por el investigador según versión modificada 1.1 del RECIST ?Beneficio clínico definido como respuesta parcial (RP), respuesta completa (RC) o enfermedad estable (EE), durante los últimos 6 meses (26 semanas) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Every 12 weeks |
Cada 12 semanas |
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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 | No |
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 | Yes |
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 | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | No |
E.8.2.2 | Placebo | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 |
Australia |
Austria |
Belgium |
Czech Republic |
Spain |
United Kingdom |
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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 of last patient, last visit (LPLV) |
fecha de la útima visita del ultimo paciente |
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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 | 5 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |