E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced or metastatic renal cell carcinoma |
Carcinoma de células renales avanzado o metastásico. |
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E.1.1.1 | Medical condition in easily understood language |
Advanced or metastatic renal cell carcinoma |
Carcinoma de células renales avanzado o 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 | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038414 |
E.1.2 | Term | Renal cell carcinoma stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10050513 |
E.1.2 | Term | Metastatic renal cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 11.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10038408 |
E.1.2 | Term | Renal cell carcinomas |
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 purpose of this study is to compare the progression free survival and the overall survival of nivolumab combined with ipilimumab to sunitinib monotherapy in patients with previously untreated Renal Cell Cancer. |
El objetivo de este estudio es comparar la Supervivencia Libre de progresión (SLP) y la Supervivencia Global (SG) de nivolumab en combinación con ipilimumab con la de la monoterapia con sunitinib en sujetos de riesgo intermedio y alto, con CCRm no tratado previamente, de acuerdo con las evaluaciones por parte del Comité de Revisión Radiológica Independiente (CRRI) |
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E.2.2 | Secondary objectives of the trial |
1.Progression-free survival 2.Overall survival 3.Objective response rate 4.Duration of objective response 5.Overall safety & tolerability 6.Disease related symptom progression 7.Health related quality of life 8.Healthcare resource utilization |
1.-Supervivencia Libre de Progresión 2.-Supervivencia Global 3.- Tasas de respuestas Objetivas (TRO) 4.- Duración de la respuesta objetiva 5.-Seguridad Global y Tolerabilidad 6.- Progresión de síntomas relacionados con la enfermedad. 7.- Calidad de vida relacionada con la salud 8.- Utilización de los recursos del cuidado de la salud. |
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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 |
Pharmacogenetics Blood Sample Amendment 01 dated 17-jul-2014, version 1.0
The objective of this Amendment is to permit the collection and storage of blood samples for use in future exploratory pharmacogenetic research. Bristol-Myers Squibb will use DNA obtained from the blood sample and health information collected from the main clinical trial, CA209214 to study the association between genetic variation and drug response. Bristol-Myers Squibb may also use the DNA to study the causes and further progression of renal cell carcinoma. Samples from this study may also be used in conjunction with pharmacogenetic research results from other clinical studies to accomplish this objective. |
Enmienda 01 de fecha 17 de julio de 2014 para la obtención demuestras de sangre para estudios de farmacogenética. El objetivo de esta enmienda es permitir a recogida y almacenamiento de muestras de sangre para su utilización en investigaciones faramacogenéticas futuras. Bristol-Myers Squibb utilizará el ADN obtenido de las muestras de sangre y la información de salud obtenida del estudio clínico principal, CA209-214 para estudiar la asociación entre variación genética y respuesta al medicamento. Bristol-Myers Squibb también utilizará el ADN para estudiar las causas y la progresión posterior del carcinoma de células renales. Las muestras de este estudio también pueden utilizarse conjuntamente con los resultados de otras investigaciones faramacogenéticas de otros estudios clínicos para cumplir este objetivo. |
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E.3 | Principal inclusion criteria |
Key Inclusion Criteria: -Histological confirmation of RCC with a clear-cell component -Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC -No prior systemic therapy for RCC with the following exception: a) One prior adjuvant or neoadjuvant therapy for completely resectable RCC if such therapy did not include an agent that targets VEGF or VEGF receptors and if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy. -Karnofsky Performance Status (KPS) of at least 70% -Measurable disease as per RECIST 1.1 -Tumor tissue (formalin-fixed paraffin-embedded (FFPE) archival or recent acquisition) must be received by the central vendor (block or unstained slides) in order to randomize a subject to study treatment. (Note: Fine Needle Aspiration [FNA] and bone metastases samples are not acceptable for submission). |
?Confirmación histológica de CCR con un componente de células claras ?CCR avanzado (no susceptible de cirugía o radioterapia curativas) o metastásico (estadio IV del AJCC) ?Ningún tratamiento sistémico previo para el CCR con la siguiente excepción: a)Un tratamiento adyuvante o neoadyuvante previo por CCR completamente resecable si dicho tratamiento no incluyó un agente dirigido contra VEGF o los receptores de VEGF y si la recidiva se produjo al menos 6 meses después de la última dosis de tratamiento adyuvante o neoadyuvante. ?Estado funcional de Karnofsky (KPS) de al menos 70% ?Enfermedad medible según los criterios RECIST 1.1 ?El tejido tumoral (fijado en formol e incluido en parafina (FFIP) de archivo o de reciente adquisición) debe ser recibido por el laboratorio central (bloques o preparaciones no teñidas) para poder aleatorizar a un sujeto al tratamiento del estudio. (Nota: no es aceptable enviar muestras de aspiración con aguja fina [AAF] ni de metástasis óseas). |
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E.4 | Principal exclusion criteria |
Key Exclusion Criteria: -Any history of or current CNS metastases. Baseline imaging of the brain is required within 28 days prior to randomization. -Prior systemic treatment with VEGF or VEGF receptor targeted therapy (including, but not limited to, sunitinib, pazopanib, axitinib, tivozanib, and bevacizumab). -Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. -Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll. -Any condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. |
?Antecedentes o presencia actual de metástasis en el SNC. Son necesarias pruebas de imagen basales del cerebro dentro de los 28 días antes de la aleatorización. ?Tratamiento sistémico previo con terapia dirigida a VEGF o el receptor de VEGF (incluidos, entre otros, sunitinib, pazopanib, axitinib, tivozanib y bevacizumab). ?Tratamiento previo con un anticuerpo anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 o anti-CTLA-4, o cualquier otro anticuerpo o fármaco dirigido específicamente a las vías de coestimulación o del punto de control de los linfocitos T. ?Presencia o antecedentes recientes de enfermedad autoinmunitaria activa conocida o de sospecha o antecedentes recientes de un síndrome que precisara corticosteroides sistémicos (> 10 mg al día de prednisona o equivalente) o medicamentos inmunosupresores excepto para síndromes de los que no se esperaría que recurrieran en ausencia de un desencadenante externo. Se permite reclutar a sujetos con vitíligo o diabetes mellitus de tipo 1 o hipotiroidismo residual debido a tiroiditis autoinmunitaria que sólo precisen tratamiento hormonal sustitutivo. ?Cualquier problema que precise tratamiento sistémico con corticosteroides (> 10 mg al día de prednisona o equivalente) u otros medicamentos inmunosupresores en el plazo de 14 días antes de la primera dosis del fármaco del estudio. Se permiten los esteroides inhalados y las dosis de esteroides de sustitución suprarrenal > 10 mg al día de prednisona o equivalente en ausencia de enfermedad autoinmunitaria activa. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints are overall survival and progression free survival. |
?La supervivencia global y la supervivencia libre de progresión son los criterios de valoración coprincipales del estudio. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
-Progression will be assessed beginning 12 wks after randomization and continuing every 6 weeks during the first 13 months and every 12 wks thereafter. -Overall survival will be followed every 2 weeks while on treatment and then every 3 months. |
-La progresión será evaluada comenzando a las 12 semanas después de la aleatorización y continuando cada 6 semanas durante los primeros 13 meses y después cada 12 semanas. -La supervivencia global se seguirá cada 2 semanas mientras continúe el tratamiento y después cada 3 meses. |
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E.5.2 | Secondary end point(s) |
1) Progression-free survival 2) Overall survival 3) Objective response rate 4) Duration of objective response 5) Overall safety & tolerability 6) Disease related symptom progression 7) Health related quality of life 8) Healthcare resource utilization |
1.- Supervivencia Libre de Progresión 2.-Supervivencia Global 3.- Tasas de respuestas Objetivas (TRO) 4.- Duración de la respuesta objetiva 5.-Seguridad Global y Tolerabilidad 6.- Progresión de síntomas relacionados con la enfermedad. 7.- Calidad de vida relacionada con la salud 8.- Utilización de los recursos del cuidado de la salud. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) see E.5.1.1 2) see E.5.1.1 3) 12 wks after randomization and continuing every 6 weeks during the first 13 months and every 12 wks thereafter 4) same as 3) 5) Continuously throughout treatment and for 100 days post treatment 6) Baseline, and then twice per 6 week cycle for first 6 months and then every 6 weeks after for duration of treatment and then every 3 months for the first 12 months of the follow-up period and then 6 monthly after that. 7) Baseline, and then twice per 6 week cycle for first 6 months and then every 6 weeks after for duration of treatment 8) same as 7) |
1- Ver E.5.1.1 2- Ver E.5.1.1. 3.-12 semanas después de la aleatorización y continuando cada 6 semanas durante los primeros 13 meses y después cada 12 semanas. 4.- igual a 3. 5.-continuamente, durante el tto. y durante 100 días post tto. 6.- En el nivel basal, y después dos veces por cada ciclo de seis semanas durante los primeros seis meses; después cada seis semanas durante la duración del tto. y cada 3 meses durante los primeros 12 meses del período de seguimiento y cada seis meses posteriormente. 7.- En el nivel basal, y después dos veces por cada ciclo de seis semanas durante los primeros seis meses; después cada seis semanas durante la duración del tto. 8.- Igual a 7. |
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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 | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarker Assessments, Outcomes Research Assessments, Immunogenicity Assessments |
Evaluaciones de biomarcadores, evaluaciones de resultados en salud, evaluaciones de 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 81 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Chile |
Colombia |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Hungary |
Ireland |
Israel |
Italy |
Mexico |
Netherlands |
Poland |
Spain |
Sweden |
Turkey |
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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Last follow-up visit of the last patient |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
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 |