E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Inoperable Locally Advanced or Metastatic Gastric Cancer that Responded to Platinum-based First-line Chemotherapy |
Cáncer gástrico inoperable localmente avanzado o metastásico que presente respuesta tras una quimioterapia de primera línea basada en el platino |
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E.1.1.1 | Medical condition in easily understood language |
Metastatic Gastric Cancer |
Cáncer gástrico metastásico |
|
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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063916 |
E.1.2 | Term | Metastatic gastric cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 maintenance therapy with BGB-290 versus placebo in patients with inoperable locally advanced or metastatic gastric cancer with a complete response (CR) or confirmed partial response (PR) after first-line platinum-based chemotherapy, as measured by: Progression-free survival (PFS) by Blinded Independent Review Committee (BIRC) assessment. |
Evaluar la eficacia del tratamiento de mantenimiento con BGB-290 en comparación con placebo en pacientes con cáncer gástrico localmente avanzado o metastásico, inoperable, con respuesta completa (complete response, CR) o respuesta parcial (partial response, PR) confirmada tras una quimioterapia de primera línea basada en el platino, en su medición por: o Supervivencia sin progresión (progression-free survival, PFS), en su determinación por un comité de revisión desconocedor del tratamiento e independiente (Blinded Independent Review Committee, BIRC) |
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E.2.2 | Secondary objectives of the trial |
To further evaluate the efficacy of maintenance therapy with BGB-290 versus placebo in patients with inoperable locally advanced or metastatic gastric cancer with a CR or confirmed PR after first-line platinum-based chemotherapy, as measured by: * Overall survival (OS) * PFS by investigator assessment * Progression-free survival 2 (PFS2) by investigator assessment * Time to second subsequent treatment (TSST) by investigator assessment * Objective response rate (ORR; CR or PR) by investigator assessment * Duration of response by investigator assessment * Time to response by investigator assessment To evaluate safety and tolerability of BGB-290 versus placebo, as measured by: * Incidence, timing, and severity of treatment-emergent adverse events (TEAEs), graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 or higher |
Evaluar ulteriormente la eficacia del tratamiento de mantenimiento con BGB-290 en comparación con placebo en pacientes con cáncer gástrico localmente avanzado o metastásico, inoperable, con una respuesta completa o una respuesta parcial confirmada tras quimioterapia de primera línea basada en el platino, en su medición por: -Supervivencia global (overall survival, OS) -Supervivencia sin progresión (PFS) -Supervivencia sin progresión 2 (PFS2) -Tiempo hasta el segundo tratamiento posterior (time to second subsequent treatment, TSST) -Tasa de respuesta objetiva ( respuesta completa o respuesta parcial) -Duración de la respuesta -Tiempo hasta la respuesta Evaluar la seguridad y la tolerabilidad de BGB-290 en comparación con placebo, en su medición mediante: -Incidencia, momento y severidad de los acontecimientos adversos surgidos durante el tratamiento, en su clasificación por grados según los criterios NCI-CTCAE, Versión 4.03 o superior. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must meet all of the following criteria to be eligible for the study: 1) Age 18 years 2) Histologically proven adenocarcinoma of the stomach or gastroesophageal junction, inoperable locally advanced or with metastatic disease a) Patients with gastric cancer overexpressing HER2 are not allowed. b) Irradiation as part of prior first-line treatment is not allowed. 3) Availability of archival tumor tissue for central laboratory determination of HRD status for randomization and exploratory biomarker analyses 4) Confirmed PR that is maintained for >=4 weeks or CR as determined by the investigator per RECIST Version 1.1 |
Los pacientes deben cumplir todos los criterios siguientes para ser elegibles para el ensayo: 1) >o= 18 años de edad 2) con adenocarcinoma de estómago o de la unión gastroesofágica, demostrado histológicamente, con enfermedad localmente avanzada o metastásica, inoperable. a) No se admitirán pacientes con cáncer gástrico con sobreexpresión de HER2 b) No se admitirán pacientes que hayan recibido radioterapia como parte del tratamiento de primera línea previo. 3) Se precisa disponer de una muestra de tejido tumoral de archivo para determinación en el laboratorio central del estado en cuanto a HRD, a fines de estratificación y para análisis exploratorio de biomarcadores. 4) Confirmación de respuesta parcial mantenida durante ≥4 semanas o una respuesta completa determinada por el investigador mediante RECIST versión 1.1. |
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E.4 | Principal exclusion criteria |
1) Unresolved acute effects of prior therapy of Grade ≥2 2) Prior treatment with a PARP inhibitor 3) Chemotherapy, biologic therapy, immunotherapy, investigational agent, anticancer Chinese medicine, or anticancer herbal remedies ≤14 days prior to randomization 4) Diagnosis of MDS 5) Leptomeningeal disease or brain metastasis 6) Previous complete gastric resection, chronic diarrhea, active inflammatory gastrointestinal disease, or any other disease causing malabsorption syndrome 7) Active bleeding disorder |
1) efectos agudos sin resolver de la terapia previa de grado ≥ 2 2) tratamiento previo con un inhibidor PARP 3) quimioterapia, terapia biológica, la inmunoterapia, agentes en investigación, medicina china contra el cáncer o remedios de herbolario contra el cáncer ≤14 días antes de la aleatorización 4) diagnóstico de MDS 5) Enfermedad leptomeníngea o metástasis cerebral 6) resección gástrica completa previa, diarrea crónica, enfermedad gastrointestinal inflamatoria activa o cualquier otra enfermedad que cause el síndrome de malabsorción 7) trastornos hemorrágicos activos |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) assessed by Blinded Independent Review Committee (BIRC) |
Supervivencia sin progresión (progression-free survival, PFS), en su determinación por un comité de revisión desconocedor del tratamiento e independiente (Blinded Independent Review Committee, BIRC) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
For PFS, there will be 1 planned interim analysis. The interim analysis will be performed when 242 PFS events (66.7% of the final target number of PFS events) have occurred at approximately 23 months after start of randomization, and the final analysis will be performed when 363 PFS events have occurred at approximately 29 months after start of randomization. |
Se ha previsto realizar un análisis intermedio de la supervivencia sin progresión una vez que se hayan producido 242 acontecimientos de la supervivencia sin progresión (el 66,7% del número final programado de acontecimientos de la supervivencia sin progresión), lo que tendrá lugar aproximadamente 23 meses después del inicio de la aleatorización, mientras que el análisis final se efectuará una vez que se hayan producido 363 acontecimientos de la supervivencia sin progresión, lo que tendrá lugar aproximadamente 29 meses después del inicio de la aleatorización. |
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E.5.2 | Secondary end point(s) |
Overall survival (OS) |
Supervivencia global |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
There will be 1 interim analysis of OS at the final of PFS analysis. The interim analysis will be performed at the final PFS analysis with positive PFS results and expected 285 deaths. The final analysis will be performed when 390 deaths have occurred. |
Habrá un análisis intermedio de la supervivencia global, a practicar en el momento del análisis final de la supervivencia sin progresión con los resultados de esta positivos y una previsión de 285 muertes. El análisis final de la supervivencia global se llevará a cabo con el objetivo de 390 muertes. |
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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 | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
tolerability |
tolerabilidad |
|
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 | 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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 49 |
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 |
Belgium |
China |
France |
Germany |
Hong Kong |
Hungary |
Italy |
Japan |
Poland |
Russian Federation |
Singapore |
Spain |
Taiwan |
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
|
LVLS |
Última visita del ultimo paciente |
|
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 | 3 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |