E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Her2‑positive, unresectable and/or metastatic breast cancer. |
Cáncer de mama HER2+ inoperable y/o metastásico |
|
E.1.1.1 | Medical condition in easily understood language |
Her2‑positive, unresectable and/or metastatic breast cancer. |
Cáncer de mama HER2+ inoperable y/o metastásico |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 identify the optimal ERBB2 mRNA cut-point predictive of DS-8201 response -Correlation of mRNA ERBB2 levels (as a continuous variable) in baseline FFPE tumor samples with overall response in the DS8201a-treated cohorts. |
-Identificar el valor de corte óptimo del ARNm del ERBB2 que prediga la respuesta a DS-8201 -Correlación de las concentraciones de ARNm de ERBB2 (como variable continua) en muestras tumorales FFIP basales con la respuesta global en las cohortes tratadas con DS8201a. |
|
E.2.2 | Secondary objectives of the trial |
-To evaluate the association of mRNA ERBB2 levels with progression-free survival and overall survival. -To evaluate the association of the PAM50 intrinsic subtypes (Luminal A, Luminal B, HER2-enriched and Basal-like) with overall response rate, progression free survival (PFS) and overall survival (OS). -To evaluate the association of immune-related genes with overall response, progression free survival (PFS) and overall survival (OS). -To design a new gene expression signature predictive of DS8201a benefit. -To evaluate the benefit of DS8201a across somatic mutations. -To correlate early changes in ctDNA with DS8201a benefit. -To identify acquired somatic mutations of resistance to DS8201a upon progression in plasma samples |
-Evaluar la asociación de las concentraciones de ARNm de ERBB2 con la supervivencia sin progresión y la supervivencia global. -Evaluar la asociación de los subtipos intrínsecos PAM50 (luminal A, luminal B, enriquecido con HER2 y seudobasal) con la tasa de respuesta global, la supervivencia sin progresión (SSP) y la supervivencia global (SG). -Evaluar la asociación de genes relacionados con la inmunidad con la respuesta global, la supervivencia sin progresión (SSP) y la supervivencia global (SG). -Diseñar una nueva firma de expresión génica predictiva del efecto beneficioso de DS8201a. -Evaluar el efecto beneficioso de DS8201a en todas las mutaciones somáticas. -Correlacionar los cambios precoces del ADNtc con el efecto beneficioso de DS8201a. -Identificar mutaciones somáticas adquiridas de resistencia a DS8201a tras la progresión en muestras de plasma |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Women ≥18 years old who previously participated in Daichi Sankyo INC. sponsored Ds8201-A-U301 and Ds8201-A-U302, consented for the obtention of a fresh biopsy or for the donation of an archival metastatic biopsy and the future use of their tumor samples in breast cancer research may be enrolled. 2.The participant (or legally acceptable representative if applicable) provides written informed consent for the study. 3.Fulfill all inclusion and exclusion criteria of the Ds8201-A-U301 or U302 trials prior to inclusion. 4.The patient who have received at least one dose of the study treatments in Ds8201-A-U301 or U302 trials. 5.Availability of FFPE tumor block, collected prior to the inclusion in Ds8201-A-U301 or U302 trial, with an associated pathology report. The tumor tissue should be of good quality based on total and viable tumor content and must be evaluated centrally for PAM50 analysis prior to enrollment. Patients whose tumor tissue is not evaluable for central testing are not eligible. -Acceptable samples include core needle biopsies for deep tumor tissue or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions or biopsies from bone metastases. -Fine needle aspiration, brushing, cell pellet from pleural effusion and lavage samples are not acceptable. 6.Must be able to provide blood sample(s). |
1.Puede reclutarse a las mujeres ≥ 18 años que participaron previamente en los estudios D8201-A-U301 y D8201-A-U302 promovidos por Daichi Sankyo INC. que hayan dado su consentimiento para la obtención de una nueva biopsia o para la donación de una biopsia metastásica de archivo y el uso futuro de sus muestras tumorales en la investigación del cáncer de mama. 2.La participante (o su representante legal si procede) da su consentimiento informado por escrito para el estudio. 3.Cumplir todos los criterios de inclusión y exclusión de los ensayos Ds8201-A-U301 o U302 antes de la inclusión. 4.La paciente ha recibido al menos una dosis de los tratamientos del estudio en los ensayos Ds8201-A-U301 o U302. 5.Disponibilidad de un bloque tumoral FFIP, obtenido antes de la inclusión en los ensayos D8201-A-U301 o U302, con un informe anatomopatológico asociado. El tejido tumoral debe ser de buena calidad basándose en el contenido tumoral total y viable, y deberá evaluarse de forma centralizada para el análisis PAM50 antes del reclutamiento. No son elegibles las pacientes cuyo tejido tumoral no sea evaluable para el análisis central. -Son muestras aceptables las biopsias con aguja gruesa de tejido tumoral profundo o biopsias por escisión, incisión, con sacabocados o con pinzas de lesiones cutáneas, subcutáneas o mucosas o las biopsias de metástasis óseas. -No son aceptables las muestras de aspiración con aguja fina, cepillado, sedimento celular de derrame pleural y de lavado. 6.Deberán poder proporcionar muestras de sangre. |
|
E.4 | Principal exclusion criteria |
Not having participated to the Daichi Sankyo INC. sponsored Ds8201-A-U301, Ds8201-A-U302 trials. |
No haber participado en los ensayos D8201-A-U301, D8201-A-U302 promovidos por Daichi Sankyo INC. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
-To identify the optimal ERBB2 mRNA cut-point predictive of DS-8201 response -Correlation of mRNA ERBB2 levels (as a continuous variable) in baseline FFPE tumor samples with overall response in the DS8201a-treated cohorts. |
-Identificar el valor de corte óptimo del ARNm del ERBB2 que prediga la respuesta a DS-8201 -Correlación de las concentraciones de ARNm de ERBB2 (como variable continua) en muestras tumorales FFIP basales con la respuesta global en las cohortes tratadas con DS8201a. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the end of the study |
Al finalizar el estudio |
|
E.5.2 | Secondary end point(s) |
-To evaluate the association of mRNA ERBB2 levels with progression-free survival and overall survival. -To evaluate the association of the PAM50 intrinsic subtypes (Luminal A, Luminal B, HER2-enriched and Basal-like) with overall response rate, progression free survival (PFS) and overall survival (OS). -To evaluate the association of immune-related genes with overall response, progression free survival (PFS) and overall survival (OS). -To design a new gene expression signature predictive of DS8201a benefit. -To evaluate the benefit of DS8201a across somatic mutations. -To correlate early changes in ctDNA with DS8201a benefit. -To identify acquired somatic mutations of resistance to DS8201a upon progression in plasma samples |
-Evaluar la asociación de las concentraciones de ARNm de ERBB2 con la supervivencia sin progresión y la supervivencia global. -Evaluar la asociación de los subtipos intrínsecos PAM50 (luminal A, luminal B, enriquecido con HER2 y seudobasal) con la tasa de respuesta global, la supervivencia sin progresión (SSP) y la supervivencia global (SG). -Evaluar la asociación de genes relacionados con la inmunidad con la respuesta global, la supervivencia sin progresión (SSP) y la supervivencia global (SG). -Diseñar una nueva firma de expresión génica predictiva del efecto beneficioso de DS8201a. -Evaluar el efecto beneficioso de DS8201a en todas las mutaciones somáticas. -Correlacionar los cambios precoces del ADNtc con el efecto beneficioso de DS8201a. -Identificar mutaciones somáticas adquiridas de resistencia a DS8201a tras la progresión en muestras de plasma |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At the end of the study. |
Al finalizar el estudio |
|
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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Identification of molecular biomarkers associated with drug response DS8201 |
Identificación de biomarcadores moleculares asociados a la respuesta al fármaco DS8201 |
|
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 | 4 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
|
Last visit last subject |
Ultima visita ultimo paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 51 |
E.8.9.1 | In the Member State concerned days | |