E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced and/or metastatic breast cancer with germline BRCA1 or BRCA2 mutations |
Cáncer de mama localmente avanzado y/o metastásico con mutaciones en la línea germinal BRCA1 o BRCA2 |
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E.1.1.1 | Medical condition in easily understood language |
Locally Advanced or Metastatic Breast Cancer with BRCA Mutation |
Cáncer de mama localmente avanzado o metastásico con mutaciones de BRCA |
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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 objective of the study is to determine the objective response rate (ORR) for each cohort treated with BMN 673 as a single agent. The ORR will be based on confirmed responses as defined by Response Evaluation Criteria in Solid Tumors (RECIST). |
El objetivo principal de este estudio es determinar la tasa de respuestas objetivas (TRO) para cada cohorte de pacientes tratados con BMN 673 en monoterapia. La TRO se basará en las respuestas confirmadas definidas por los Criterios de evaluación de la respuesta en tumores sólidos (RECIST). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to evaluate the following: - Clinical benefit response (CBR) rate as defined as CR + partial response (PR) + SD lasting ? 24 weeks - Duration of response (DOR) for CR and PR - PFS -Overall survival (OS) -Safety -Pharmacokinetics of BMN 673 |
Los objetivos secundarios del estudio son determinar lo siguiente: - Tasa de beneficio clínico (TBC), definida como los casos de respuesta completa (RC) + respuesta parcial (RP) + enfermedad estable (EE) que se prolonguen durante ? 24 semanas. - Duración de la respuesta (DdR), para los casos de RC y RP. - Supervivencia sin progresión (SSP). - Supervivencia global (SG). - Seguridad. - Farmacocinética de BMN 673. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria: Histologically or cytologically confirmed carcinoma of the breast. Locally advanced and/or metastatic disease. Deleterious or pathogenic germline BRCA 1 or BRCA 2 mutation. Prior chemotherapy: Cohort 1) PR or CR to prior platinum-containing regimen for metastatic disease with disease progression > 8 weeks following the last dose of platinum; or Cohort 2) > 2 prior chemotherapy regimens for metastatic disease and no prior platinum for metastatic disease. ECOG performance status ? 1. Have adequate organ function. |
Criterios de inclusión: Carcinoma de mama, confirmado histológica o citológicamente. Enfermedad localmente avanzada y/o metastásica. Presencia de una mutación nociva o patogénica en línea germinal en los genes BRCA1 o BRCA2. Quimioterapia previa: Cohorte 1) pacientes que hubieran presentado RP o RC con un tratamiento previo que incluyera platino y que se hubiera administrado para tratar la enfermedad metastásica, que hubieran experimentado progresión de la enfermedad > 8 semanas después de la última dosis de platino. Cohorte 2) > 2 tratamientos quimioterápicos previos para tratar la enfermedad metastásica, y no haber recibido platino para tratar la enfermedad metastásica. Categoría funcional del Eastern Cooperative Oncology Group (ECOG) ? 1. Tener una función orgánica adecuada. |
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E.4 | Principal exclusion criteria |
Prior enrollment into a clinical trial of a PARP inhibitor. CNS metastasis except adequately treated brain metastasis documented by baseline CT or MRI scan that has not progressed since previous scans and that does not require corticosteroids for management of CNS symptoms. Prior malignancy except for prior BRCA-associated cancer as long as there is no current evidence of the prior cancer, carcinoma in situ of the cervix or non-melanoma skin cancer, and a cancer diagnosed and definitively treated >5 years prior to study enrollment with no subsequent evidence of recurrence. Known to be HIV positive, active hepatitis C virus, or active hepatitis B virus. Known hypersensitivity to any of the components of BMN 673. |
Haber sido reclutado anteriormente en un ensayo clínico en el que se haya evaluado un inhibidor de la PARP. Metástasis en el SNC Excepto metástasis cerebrales que se hubieran tratado adecuadamente, documentadas en el momento basal mediante tomografía computarizada (TC) o resonancia magnética (RM), que no hayan progresado respecto a pruebas de imagen previas, y que no requieran la administración de corticosteroides para tratar los síntomas relacionados con el SNC. Neoplasias malignas previas, excepto en cáncer previo relacionado con los genes BRCA, sin que en la actualidad se observe ningún indicio del cáncer previo,carcinoma in situ del cuello uterino o cáncer de piel no melanomatoso, y en cáncer diagnosticado y que se haya tratado definitivamente > 5 años antes, sin posteriores indicios de recurrencia. Presentar infección por el virus de la inmunodeficiencia humana, infección activa por virus de la hepatitis C o por virus de la hepatitis B. Hipersensibilidad conocida a cualquiera de los componentes de BMN 673. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall response rate (ORR) |
Tasa de respuestas objetivas (TRO) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Anticipated in about 24-30 months following first patient enrolled |
Previsto en 24-30 meses después del primer paciente incluido |
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E.5.2 | Secondary end point(s) |
Clinical Benefit Response (CBR) (CR + PR + SD lasting ? 24 weeks), Duration of Response (DOR) for responding subjects (CR + PR, subset analysis) by IRF evaluation, Progression Free Survival (PFS), and Overall Survival (OS) |
Los criterios secundarios de valoración de la eficacia son la Tasa de Beneficio clínico,TBC (RC + RP + EE que se prolongue ? 24 semanas), Duración de la respuesta (DdR) para los pacientes que respondan (RC + RP, subconjunto de análisis) de acuerdo con la evaluación realizada por el CRI, la Supervivencia sin progresión (SSP) y la Supervivencia global (SG). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Primary efficacy analysis will be performed after the last subject has had the opportunity to be confirmed as a responder if the subject responds within 18 weeks |
El análisis principal de la eficacia se realizará una vez que se haya tenido la oportunidad de confirmar la condición de respondedor del último paciente, si el paciente responde en el transcurso de 18 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 | Yes |
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 | 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 | No |
E.8.1.1 | Randomised | No |
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 | 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 | 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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 |
France |
Germany |
Spain |
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
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LVLS |
Última visita del último 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 | 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 |