E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Unresectable/Metastatic Esophageal Squamous Cell Carcinoma(ESCC) |
Carcinoma esofágico epidermoide avanzado no resecable/metastásico |
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E.1.1.1 | Medical condition in easily understood language |
Advanced Unresectable or Metastatic Esophageal Squamous Cell Carcinoma(ESCC) |
Carcinoma esofágico epidermoide avanzado no resecable/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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055476 |
E.1.2 | Term | Esophageal squamous cell carcinoma |
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 compare the overall survival (OS) following treatment with BGB-A317 vs. investigator chosen chemotherapy (ICC) when given as second line treatment in patients with advanced unresectable/metastatic Esophageal Squamous Cell Carcinoma (ESCC) |
• Comparar la supervivencia global (overall survival, OS) tras el tratamiento con BGB-A317 frente a la quimioterapia elegida por el investigador (investigator chosen chemotherapy, ICC) en su administración como tratamiento de segunda línea a pacientes con carcinoma esofágico epidermoide (esophageal squamous cell carcinoma, ESCC) avanzado no resecable/metastásico |
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E.2.2 | Secondary objectives of the trial |
•The following secondary endpoints will be compared between BGB-A317 and ICC as assessed by Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria: o Objective response rate (ORR) o Progression-free survival (PFS) o Duration of response (DOR) • To compare patient reported outcomes of health-related quality of life (HRQoL) between the BGB-A317 and the chemotherapy treatments • To compare the safety and tolerability between BGB-A317 and the chemotherapy treatments |
• Comparar los criterios secundarios de valoración siguientes, a juzgar por el investigador según los criterios de evaluación de la respuesta en tumores sólidos (Response Evaluation Criteria in Solid Tumors, RECIST) v1.1, entre BGB-A317 y la quimioterapia elegida por el investigador: o Tasa de respuesta objetiva (objective response rate, ORR) o Supervivencia sin progresión (progression-free survival, PFS) o Duración de la respuesta (duration of response, DOR) • Comparar los desenlaces comunicados por los pacientes sobre la calidad de vida relacionada con la salud (health-related quality of life, HRQoL) entre BGB-A317 y los tratamientos de quimioterapia • Comparar la seguridad y la tolerabilidad entre BGB-A317 y los tratamientos de quimioterapia |
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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 |
Safety Run-in Substudy Investigating Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Anti-PD-1 Monoclonal Antibody BGB A317 in Japanese Patients with Advanced Unresectable/Metastatic Esophageal Squamous Cell Carcinoma Protocol Identifier: BGB-A317-302 Substudy Primary Study Objectives: • To assess the safety and tolerability of BGB-A317 in Japanese patients with advanced unresectable esophageal squamous cell carcinoma (ESCC) • To confirm the pivotal Phase 3 dose of BGB-A317 in Japanese patients • To characterize the pharmacokinetics of BGB-A317 in Japanese patients Secondary Study Objectives: • To assess the preliminary antitumor activity of BGB-A317 • To assess host immunogenicity to BGB-A317 |
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E.3 | Principal inclusion criteria |
1. Pathologically (histologically or cytologically) confirmed diagnosis of esophageal squamous cell carcinoma (ESCC) 2. Tumor progression during or after first-line treatment for advanced unresectable / metastatic ESCC 3. At least one measurable/evaluable lesion by RECIST v1.1 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 prior to randomization 5. Adequate End organ function |
1. Diagnóstico de carcinoma esofágico epidermoide confirmado por anatomía patológica (histología o citología). 2. Progresión del tumor durante el tratamiento de primera línea por enfermedad avanzada no resecable/ metastásica o después de este. 3. Todos los pacientes también deben presentar >=1 lesión evaluable según los RECIST v1.1 en el plazo de los 28 días anteriores a la aleatorización. 4. Puntuación del estado funcional del ECOG (Eastern Cooperative Oncology Group) <=1 5. Nivel de funcionamiento orgánico adecuado. |
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E.4 | Principal exclusion criteria |
1. Receipt of 2 or more prior systemic treatments for advanced/metastatic unresectable ESCC 2. History of gastrointestinal perforation and /or fistula or aorto-esophageal fistula within 6 months prior to randomization 3. Apparent tumor invasion into organs located adjacent to the esophageal disease site (eg, aorta or respiratory tract) at an increased risk of fistula in the study treatment assessed by investigator 4. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage 5. Received prior therapies targeting PD-1 or PD-L1 6. Prior malignancy active within the previous 2 years (exceptions include the tumor under investigation in this trial, and locally recurring cancers that have undergone curative treatment, such as resected basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the prostate, cervix or breast) 7. Active brain or leptomeningeal metastasis. 8. Has active autoimmune disease or history of autoimmune diseases at high risk for relapse 9. Known history of, or any evidence of interstitial lung disease, non-infectious pneumonitis, pulmonary fibrosis diagnosed based on imaging or clinical findings, or uncontrolled systemic diseases, including diabetes, hypertension, acute lung diseases, etc 10. Known history of Human Immunodeficiency Virus (HIV) 11. Has cardiovascular risk factors 12. Pregnant or breastfeeding woman. |
1. Recepción de 2 o más tratamientos sistémicos previos para ESCC avanzado / metastásico no resecable. 2. Antecedentes de perforación gastrointestinal y / o fístula o fístula aortoesofágica dentro de los 6 meses previos a la aleatorización. 3. Invasión tumoral aparente en órganos localizados adyacentes al sitio de la enfermedad esofágica (p. Ej., Aorta o vías respiratorias) con un mayor riesgo de fístula en el tratamiento del estudio evaluado por el investigador. 4. Derrame pleural incontrolable, derrame pericárdico, o ascitis que requieren drenaje frecuente. 5. Recibió terapias anteriores dirigidas a PD-1 o PD-L1. 6. Malignidad previa activa dentro de los 2 años previos (las excepciones incluyen el tumor bajo investigación en este ensayo y cánceres localmente recurrentes que han sido sometidos a tratamiento curativo, como cáncer de piel de células escamosas o basoescamoso resecado, cáncer superficial de vejiga o carcinoma in situ de próstata, cuello uterino o mama). 7.Metástasis cerebral activa o leptomeníngea. 8.Tiene enfermedad autoinmune activa o historia de enfermedades autoinmunes con alto riesgo de recaída. 9. Antecedentes conocidos de, o alguna evidencia de enfermedad pulmonar intersticial, neumonitis no infecciosa, fibrosis pulmonar diagnosticada en base a hallazgos por imagen o clínicos, o enfermedades sistémicas no controladas, incluyendo diabetes, hipertensión, enfermedades pulmonares agudas, etc. 10. Antecedente conocido de Virus de Inmunodeficiencia Humana (VIH). 11. Tiene factores de riesgo cardiovasculares. 12. Mujeres embarazadas o en periodo de lactancia. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• OS - defined as the time from the date of randomization until the date of death due to any cause |
SG-Supervivencia Global-definida como el tiempo desde la fecha de aleatorización hasta la fecha de la muerte debida a cualquier causa. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The final analysis of OS will occur at approximately 3 years. |
El análisis final de SG ocurrirá a los 3 años aproximadamente. |
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E.5.2 | Secondary end point(s) |
• ORR - defined as the proportion of patients who had complete response (CR) or partial response (PR) assessed by the Investigators per RECIST v1.1 • PFS - defined as the time from the date of randomization to the date of first documentation of disease progression assessed by the Investigators per RECIST v1.1 or death, whichever occurs first • DOR- defined as the time from the first determination of an objective response until the first documentation of progression assessed by the Investigators per RECIST v1.1 or death, whichever comes first • HRQoL assessment • The incidence and severity of adverse events |
-Tasa de respuesta objetiva ORR) :definida como el porcentaje de pacientes con respuesta completa (complete response, CR) o respuesta parcial (partial response, PR) a juzgar por la evaluación del investigador según los RECIST v1.1 -Supervivencia sin progression (PFS): definida como el tiempo transcurrido desde la fecha de la aleatorización hasta la fecha de la primera documentación de progresión de la enfermedad, a juzgar por la evaluación del investigador según los RECIST v1.1, o la muerte, eligiéndose la primera de estas situaciones que tenga lugar -Duración de la respuesta (DOR): definida como el tiempo transcurrido desde la primera determinación de una respuesta objetiva hasta la primera documentación de progresión, a juzgar por la evaluación del investigador según los RECIST v1.1, o la muerte, eligiéndose la primera de estas situaciones que tenga lugar. - Evaluación de la Calidad de vida relacionada con la salud (HRQoL) -Incidencia y severidad de los acontecimientos adversos. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
ORR as assessed by investigator PFS as assessed by investigator DOR as assessed by investigator HRQoL as assessed by European EORTC QLQ-C30 index, the European esophageal cancer specific module OES18, and the EQ-5D-5L. Incidence and severity of adverse events according to NCI-CTCAE v4.03 |
Tasa de respuesta objetiva (ORR) evaluada por el investigador. Supervivencia sin progresión (PFS) evaluada por el investigador. Duración de la respuesta (DOR) evaluada por el investigador. Calidad de vida relacionada con la salud, mediante evaluación del estado de salud general del sujeto con el cuestionario de calidad de vida de la European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, el módulo de cáncer esofágico de la EORTC QLQ-OES18 y el EQ-5D-5L. Incidencia y severidad de los acontecimientos adversos, según los National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03 |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Assessment of Immunogenicity |
Evaluación de la inmunogenicidad |
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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 | 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 | 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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 54 |
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 |
Belgium |
France |
Germany |
Italy |
Japan |
Korea, Republic of |
Spain |
Taiwan |
United Kingdom |
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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 Sujeto |
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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 | 9 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |