E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Small Cell Lung Cancer |
Cáncer de pulmón microcítico |
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E.1.1.1 | Medical condition in easily understood language |
Small Cell Lung Cancer |
Cáncer de pulmón microcítico |
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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 | PT |
E.1.2 | Classification code | 10041067 |
E.1.2 | Term | Small cell lung 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 |
The primary objective is to assess treatment with rovalpituzumab tesirine imrpoves objective response rate (ORR) and overall survival rate (OS) compared to topotecan in subjects with DLL3high SCLC who have first disease progression during or following front-line platinum based chemotherapy. |
Determinar si el tratamiento con rovalpituzumab tesirina mejora la tasa de respuestas objetivas (TRO) y la supervivencia global (SG) en comparación con topotecán en pacientes con CPM avanzado o metastásico y DLL3alta que presentan una primera progresión de la enfermedad durante o después de una primera línea de quimioterapia con platino. |
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E.2.2 | Secondary objectives of the trial |
1) Assess if treatment with rovalpituzumab tesirine improves progression free survivial (PFS) compared to topotecan in subjects with advanced or metastatic DLL3high SCLC who have first disease progression during or following front-line platinum based chemotherapy, 2) Compare the duration of object response between two arms, 3) To assess the pharmacokinetics (PK) and immunogenicity of rovalpituzumab tesirine, 4) Assess the effect on patient reported outcomes (i.e. health-related quality of life and symptom assessment) due to treatment with rovalpituzumab tesirine compared to topotecan in subects with DLL3high SCLC who have first disease progression during or following front-line platinum based chemotherapy. |
1) Determinar si el tratamiento con rovalpituzumab tesirina mejora la supervivencia sin progresión (SSP) en comparación con topotecán en pacientes con CPM avanzado o metastásico y DLL3alta que presentan una primera progresión de la enfermedad durante o después de una primera línea de quimioterapia con platino. 2) Comparar la duración de la respuesta objetiva entre los dos grupos, 3) Evaluar la farmacocinética (PK) y la inmunogenicidad del rovalpituzumab tesirina, 4) Evaluar el efecto en los resultados comunicados por los pacientes (es decir, valoración de la calidad de vida relacionada con la salud y de los síntomas) del tratamiento con rovalpituzumab tesirina en comparación con topotecán en pacientes con CPM avanzado o metastásico y DLL3alta que presentan una primera progresión de la enfermedad durante o después de una primera línea de quimioterapia con platino. |
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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 |
Optional Tumor Tissue at Time of Progression for Exploratory Research |
Tejido tumoral opcional en el momento de la progresión para la investigación exploratoria |
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E.3 | Principal inclusion criteria |
1) Subjects must be an age of 18 years or older, providing written informed consent 2) Histologically or cytologically confirmed advanced or metastatic SCLC with documented first disease progression after or during front-line platinum-based systemic regimen. 3) Tumor must have high DLL3 expression (DLL3high) defined as having > 75% tumor cells staining positive according to the VENTANA DLL3 (SP347) IHC Assay. Archived or fresh tumor material can be used for the DLL3 testing. 4) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5) Females of childbearing potential must have a negative serum pregnancy test result at Screening, and a negative urine pregnancy test at randomization. Females of non-childbearing potential (either postmenopausal or permanently surgically sterile) at Screening do not require pregnancy testing. |
1) Adultos de 18 o más años de edad que hayan otorgado el consentimiento informado por escrito. 2) CPM avanzado o metastásico confirmado mediante examen histológico o citológico con primera progresión documentada de la enfermedad durante o después de una pauta sistémica de primera línea con platino. 3) El tumor debe tener una expresión elevada de DLL3 (DLL3alta) definida como ≥75% de células tumorales que den positivo en el análisis de VENTANA DLL3 (SP347) IHC. Se puede usar material tumoral de archivo y reciente para el análisis de DLL3. 4) Estatdo functional del Eastern Cooperative Oncology Group (ECOG) de 0 o 1. 5) Las mujeres en edad fértil deberán obtener un resultado negativo en una prueba de embarazo en suero efectuada en la visita de selección y en una prueba de embarazo en orina realizada el día de la aleatorización. Las mujeres que no estén en edad fértil (posmenopáusicas o esterilizadas quirúrgicamente según la definición del protocolo) en la selección no tendrán que hacerse pruebas de embarazo. |
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E.4 | Principal exclusion criteria |
1) Any significant medical condition that, in the opinion of the investigator or Sponsor, may place the subject at undue risk from the study, including but not necessarily limited to uncontrolled hypertension and/or diabetes, clinically significant pulmonary disease or neurological disorder (e.g., seizure disorder active within 6 months) 2) Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class III – IV within 6 months prior to their first dose of study drug. 3) Subject has known leptomeningeal metastases 4) Subject has Isolated CNS disease progression with no evidence of progression outside of CNS 5) Subject has more than one prior systemic therapy regimen for SCLC (prior systemic maintenance therapy following front-line platinum based regimen, administered as part of clinical trial is allowed) |
1) Cualquier enfermedad importante que, en opinión del investigador o el promotor, suponga un riesgo indebido para el paciente por participar en el estudio, por ejemplo, hipertensión o diabetes no controladas o enfermedad pulmonar o trastorno neurológico clínicamente significativos (p. ej., trastorno convulsivo activo en los 6 meses anteriores). 3) Metástasis leptomeníngeas confirmadas. 4) Progresión aislada de la enfermedad en el SNC sin signos de progresión fuera del SNC. 5) Más de una pauta de tratamiento sistémico previa para el CPM (se permitirá un tratamiento de mantenimiento sistémico previo después de una pauta de primera línea con platino administrado como parte de un ensayo clínico). |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Objective response rate (ORR) - Overall survival (OS) |
- Tasa de Respuestas Objetivas (TRO) - Supervivencia Global (SG) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Objective Response Rate will be performed in the response-evaluable set, defined as all randomized subjects with measureable disease at baseline who have had a minimum follow-up of 5 months at the time of analysis. - Overall Survival is defined as the time from the date of randomization to the date of death form any cause (i.e., date of subject's death - date of randomization +1). |
- La Tasa de Respuesta Objetiva se realizará en el conjunto de respuestas evaluables, definida como todos los sujetos aleatorizados con enfermedad medible que han tenido un seguimiento mínimo de 5 meses en el momento del análisis. - La Supervivencia Global (SP) se define como el tiempo desde la fecha de la aleatorización hasta la fecha de la muerte de cualquier causa (es decir, la fecha de la muerte del sujeto - fecha de la asignación al azar +1). |
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E.5.2 | Secondary end point(s) |
- Progression-free survival (PFS) based on the CRAC per RECIST v1.1, - Duration of objective response (DOR) based on the CRAC per RECIST v1.1, - Patient reported outcomes (PROs). |
- Supervivencia sin progression (SSP) se obtendrá en función de la progresión radiológica (Central Radiographic Assessment Committee (CRAC)) conforme a los criterios RECIST, versión 1.1, - Druracion respuesta objetiva (DRO) se obtendrá en función de la progresión radiológica (Central Radiographic Assessment Committee (CRAC)) conforme a los criterios RECIST, versión 1.1, - Resultados comunicados por los pacientes (RCP). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- PFS is based on independent review of tumor assessment, defined as the time from randomization to documented CRAC-assessed disease progression or death from any cause (whichever occurs earlier). - DOR is defined as the time between the date of first response (CR or PR, whichever is recorded first) to the date of the first documented tumor progression (per RECIST 1.1) or death due to any cause, whichever comes first. |
E.5.2.1 Tiempo(s) de evaluación de este objetivo: - PFS se basa en la revisión independiente de la evaluación de los tumores, definida como el tiempo transcurrido desde la aleatorización hasta la progresión de la enfermedad documentada por CRAC o la muerte por cualquier causa (lo que ocurra antes). - DOR se define como el tiempo transcurrido entre la fecha de la primera respuesta (CR o PR, la que se registra primero) hasta la fecha de la primera progresión documentada del tumor (según RECIST 1.1) o la muerte por cualquier causa, lo que ocurra primero. |
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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 | 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 |
Performance status Quality of Life |
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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 | 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) | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
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 |
Brazil |
Canada |
China |
Japan |
Korea, Republic of |
Mexico |
Singapore |
Taiwan |
Turkey |
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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The end-of-study is defined as the date of the last subject's last visit, or the date of the last subject's last survival follow-up contact, whichever is later. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |