E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HER2-Negative Metastatic or Locally Advanced Unresectable BRCA-Associated mutation (BRCA1 and BRCA2) Breast Cancer |
Cáncer de mama asociado a la mutación BRCA (BRCA1 y BRCA2), HER2 negativo, no resecable, metastásico o localmente avanzado |
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E.1.1.1 | Medical condition in easily understood language |
Metastatic or Locally Advanced Unresectable BRCA-Associated Breast Cancer |
Cáncer de mama asociado a BRCA no resecable metastásico o localmente avanzado |
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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 | 17.0 |
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 |
The primary endpoint is to assess the progression-free survival (PFS) of veliparib in combination with carboplatin (C) and paclitaxel (P) compared to placebo with C/P in subjects with a BRCA1 and/or BRCA2 Mutation and in Her-2 Negative Metastatic or Locally Advanced Unresectable Breast Cancer |
El objetivo principal es evaluar la supervivencia sin progresión (SSP) de veliparib en combinación con carboplatino (C) y paclitaxel (P) frente a placebo con C/P en sujetos con mutaciones de BRCA1 y/o BRCA2 y cáncer de mama HER2 negativo, no resecable, metastásico o localmente avanzado. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to assess overall survival (OS), clinical benefit rate (CBR), objective response rate (ORR), Progression Free Survival 2 (PFS2) and duration of overall response (DOR) in subjects treated with veliparib in combination with C/P versus subjects treated with placebo with C/P. |
Los objetivos secundarios del estudio son evaluar la supervivencia global (SG), la tasa de beneficio clínico (TBC), la tasa de respuesta objetiva (TRO), la Supervivencia Sin Progresión 2 (SSP2) y la duración de la respuesta global (DRG) en sujetos tratados con veliparib en combinación con C/P frente a sujetos tratados con placebo con C/P. |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenetic substudy - optional blood test PD plasma samples Tissue biospies - optional test |
Subestudio farmacogenético ? análisis de sangre opcional Muestras de plasma para farmacodinámica (FD) Biopsias de tejido ? Prueba opcional |
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E.3 | Principal inclusion criteria |
-Men and women ? 18 years of age; - Histologically or cytologically confirmed breast cancer that is either locally advanced or metastatic; - Locally advanced breast cancer must not be amenable to surgical resection or radiation with curative intent; - Suspected deleterious or deleterious BRCA1 and/or BRCA2 germline mutation; Measurable or non-measurable (but radiologically evaluable) disease per RECIST version 1.1 on computed tomography (CT) scan. |
Varones y mujeres ? 18 años; - Cáncer de mama confirmado mediante histología o citología, localmente avanzado o metastásico; - El cáncer de mama localmente avanzado no puede ser objeto de resección quirúrgica ni de radiación con fines curativos; - Mutación de la línea germinal en BRCA1 y/o BRCA2 con efectos perjudiciales sospechados o confirmados; - Enfermedad mensurable o no mensurable (pero radiológicamente evaluable) conforme a los criterios RECIST, versión 1.1, en la tomografía computarizada (TC). |
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E.4 | Principal exclusion criteria |
- Received anticancer agent(s) or an investigational agent within 21days prior to C1D-2 or radiotherapy within 28 days prior to C1D-2; - More than 2 prior lines of cytotoxic chemotherapy (e.g., gemcitabine, doxorubicin, capecitabine) for metastatic disease; - More than one prior line of platinum therapy for breast cancer; - Subjects who have progressed on platinum therapy or recurred within 12 months of platinum therapy will be excluded; - Prior therapy with PARP inhibitors - Prior taxane therapy administered for the treatment of metastatic breast cancer with exceptions (see protocol); - Subjects with active brain metastases or leptomeningeal disease. |
- Haber recibido fármacos antineoplásicos o un fármaco en investigación en los 21 días anteriores al D-2C1 o radioterapia en los 28 días anteriores al D-2C1; - Más de dos líneas previas de quimioterapia citotóxica (por ejemplo, gemcitabina, doxorubicina, capecitabina) para la enfermedad metastásica; - Más de una línea previa de tratamiento con platino para el cáncer de mama; - Se excluirá a los sujetos que hayan presentado progresión con tratamiento de platino o que hayan recidivado en los 12 meses siguientes al tratamiento con platino; - Tratamiento previo con inhibidores de PARP; - Tratamiento previo con taxanos administrado para el cáncer de mama metastásico con excepciones (ver protocolo); - Sujetos con metástasis cerebrales activas o enfermedad leptomeníngea. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival |
Supervivencia Sin Progresión |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Progression-free Survival (PFS): will be evaluated according to radiographic progression per RECIST (version 1.1) determined by the Central Imaging Center and survival information (death). Radiologic tumor response and disease progression will be assessed by CT scan utilizing RECIST (version 1.1). Assessments will be performed at Screening, at 9-week intervals thereafter, and at the Final Visit, if not performed within the last 4 weeks. |
Supervivencia Sin Progresión (SSP): se evaluará en función de la progresión radiográfica conforme a los criterios RECIST, versión 1.1., determinada por el servicio central de diagnóstico por imagen y los datos de supervivencia (mortalidad). La respuesta tumoral radiológica y la progresión de la enfermedad se evaluarán mediante TC utilizando la versión 1.1 de los criterios RECIST. Las evaluaciones se realizarán en la visita de selección, a intervalos de 9 semanas (desde el D-2C1) posteriormente y en la visita final, si no se han efectuado en las últimas 4 semanas. |
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E.5.2 | Secondary end point(s) |
Clinical benefit rate (CBR) Objective Response Rate (ORR) Duration of Overall Response (DOR) Overall Survival (OS) PFS2 |
Tasa de Beneficio Clínico (TBC) Tasa de Respuesta Objetiva (TRO) Duración de la Respuesta Global (DRG) Supervivencia Global (SG) Supervivencia Sin Progresión 2 (SSP2) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Clinical benefit rate, Objective Response Rate and Duration of Overall Response evaluated according to radiographic progression per RECIST (version 1.1) determined by the Central Imaging Center. Assessments will be performed at Screening, at 9-week intervals thereafter, and at the Final Visit. Overall Survival (OS): will be evaluated according to survival information and post treatment information collected every 2 months beginning on the date the subject is registered off study and until the endpoint of death, the subject is lost to follow-up or until the study termination by AbbVie. PFS2: will be evaluated according to survival information and post treatment information collected every 2 months. |
Tasa de beneficio clínico, tasa de respues objetiva y duración de la respues global: se evalu en función de la progresión radiográfica conforme a los criterios RECIST (versión 1.1), determi por el servicio central de diagnóstico por imagen. Las evaluacio. se realizarán en la visita de selec., a interv de 9 sem (desde el D-2C1) posterior. y en la visita final. Supervi global (SG): se evalu de confor con los datos de supervi y la inform posterior al tto recogidos a interv de 2 meses empezando en la fecha en que se documente la retirada del sujeto y hasta el momento de su muerte, su pérdida para el segui. o la terminación del estudio por decisión de AbbVie. SSP2: se evaluará de confor con los datos de supervivencia y la infor posterior al tto recogidos a interva de 2 meses. |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of life |
Calidad de vida |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.4 | Double blind | Yes |
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) | 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 | 105 |
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 |
Argentina |
Australia |
Austria |
Belarus |
Belgium |
Canada |
Chile |
Colombia |
Czech Republic |
Denmark |
Estonia |
Finland |
France |
Germany |
Hungary |
Israel |
Italy |
Japan |
Korea, Democratic People's Republic of |
Latvia |
Lithuania |
Mexico |
Netherlands |
Norway |
Poland |
Portugal |
Puerto Rico |
Romania |
Russian Federation |
Singapore |
South Africa |
Spain |
Sweden |
Taiwan |
Turkey |
Ukraine |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
|
The end-of-study is defined as the date of last subject's last visit. |
Se define como fecha final del estudio la fecha de la última visita del último sujeto. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |