E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Renal Cell Carcinoma |
carcinoma de células renales |
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E.1.1.1 | Medical condition in easily understood language |
Kidney Cancer |
Cancer de Riñon |
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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 | 10050076 |
E.1.2 | Term | Metastatic renal 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 |
The objective of this study is to evaluate the efficacy and safety of cabozantinib in combination with nivolumab and ipilimumab versus nivolumab and ipilimumab in previously untreated subjects with intermediate- and poor-risk advanced or metastatic RCC. |
El objetivo de este estudio es evaluar la eficacia y la seguridad de cabozantinib combinado con nivolumab e ipilimumab en comparación con nivolumab e ipilimumab en pacientes con CCR avanzado o metastásico de riesgo intermedio y desfavorable no tratados previamente. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologically confirmed advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) renal cell carcinoma with a clear-cell component. - Intermediate- or poor-risk RCC as defined by International Metastatic RCC Database Consortium (IMDC) criteria. - Measurable disease per RECIST 1.1 as determined by the Investigator. - Karnofsky Performance Status (KPS) ≥ 70%. - Adequate organ and marrow function. |
- Carcinoma de células renales avanzado (no susceptible de cirugía ni radioterapia curativas) o metastásico (estadio IV del AJCC) confirmado histológicamente con un componente de células claras, incluidos los pacientes que también presenten una característica sarcomatoide. - CCR de riesgo intermedio o desfavorable, definido por los criterios del IMDC - Enfermedad mensurable con arreglo a los criterios RECIST 1.1, según lo determinado por el investigador - Estado funcional de Karnofsky (EFK) ≥ 70 %. - Adecuada función de los órganos y la médula ósea |
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E.4 | Principal exclusion criteria |
- Prior systemic therapy for unresectable locally advanced or metastatic RCC including investigational agents. - Uncontrolled, significant intercurrent or recent illness including, but not limited to serious cardiovascular disorders (including uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment), GI disorders associated with high risk for perforation or fistula formation, tumors invading GI tract, bowel obstruction, intra-abdominal abscess, clinically significant bleeding events, cavitating pulmonary lesions, or lesion invading major pulmonary blood vessels. -Other clinically significant disorders such as: i. Any active, known or suspected autoimmune disease. ii. Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. iii. Active infection requiring systemic treatment. Acute or chronic hepatitis B or C infection, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or known positive test for tuberculosis infection. -Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks prior to randomization. Prior laparoscopic nephrectomy within 4 weeks prior to randomization. Minor surgeries within 10 days prior to randomization. Subjects must have complete wound healing from major surgery or minor surgery before randomization. - Any other active malignancy at time of randomization or diagnosis of another malignancy within 3 years prior to randomization that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast. |
Tratamiento sistémico previo para el CCR localmente avanzado irresecable o metastásico, incluidos fármacos en investigación - Enfermedad intercurrente o reciente no controlada y significativa incluido, pero no limitado a serios trastornos cardiovasculares (Incluido Hipertensión no controlada, definida como una presión arterial (PA) mantenida > 150 mm Hg de sistólica o > 90 mm Hg de diastólica a pesar de recibir un tratamiento antihipertensivo óptimo. Trastornos digestivos, incluidos los que entrañen un riesgo elevado de perforación o formación de fistulas, i. Tumores que invadan el tubo digestivo, úlcera péptica activa, enfermedad inflamatoria intestinal, diverticulitis, colecistitis, colangitis o apendicitis sintomática, pancreatitis aguda u obstrucción aguda del conducto pancreático o colédoco u obstrucción de la salida gástrica. iFístula abdominal, perforación gastrointestinal, obstrucción intestinal o absceso intrabdominal. Lesiones pulmonares con cavitación o manifestación de una enfermedad endobronquial conocida. Lesiones que invadan los vasos sanguíneos pulmonares principales. f. Otros trastornos clínicamente significativos como: i. Confirmación o sospecha de enfermedad autoinmunitaria activa. Cualquier enfermedad que necesite tratamiento sistémico con corticosteroides (> 10 mg de equivalente de prednisona al día) u otros fármacos inmunodepresores en los 14 días previos a la aleatorización. Infección activa con necesidad de tratamiento sistémico. Infección aguda o crónica por el virus de la hepatitis B o C, infección conocida por el virus de la inmunodeficiencia humana (VIH) o enfermedad relacionada con el síndrome de inmunodeficiencia adquirida (SIDA), o prueba positiva conocida de infección tuberculosa. iAntecedentes de fibrosis pulmonar idiopática, neumonía organizada, neumonitis inducida por fármacos, neumonitis idiopática o signos de neumonitis activa en la TC de tórax de la selección Intervención de cirugía mayor (p. ej., cirugía digestiva, extirpación o biopsia de metástasis cerebrales) en los 8 meses previos a la aleatorización. Nefrectomía laparoscópica previa en las 4 semanas anteriores a la aleatorización. Intervenciones de cirugía mayor en los 10 días previos a la aleatorización. Los pacientes deberán presentar una cicatrización completa de la herida de una intervención de cirugía mayor o menor antes de la aleatorización Cualquier otra neoplasia maligna activa en el momento de la aleatorización o diagnóstico de otra neoplasia maligna en los 3 años previos a la aleatorización que requiera tratamiento activo, excepto cánceres localmente curables que se hayan curado aparentemente, como cáncer basocelular o espinocelular de piel, cáncer superficial de vejiga o carcinoma in situ de próstata, cuello uterino o mama. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Duration of PFS (Progression-Free Survival), per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), by Blinded Independent Radiology Committee (BIRC) |
Duración de la SSP, conforme a los Criterios de evaluación de la respuesta en tumores sólidos, versión 1.1 (RECIST 1.1), por el Comité radiológico independiente y enmascarado (BIRC). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The first tumor assessment after randomization should be performed at W10D1 (± 7 days). Subsequent tumor assessments should be performed every 8 weeks (± 7 days) from randomization through Week 50. Upon completion of 50 weeks on study, these assessments will be performed every 12 weeks (± 7 days). Additional imaging of potential disease sites should be performed whenever radiographic PD is suspected. |
La primera evaluación del tumor después de la aleatorización debe efectuarse el D1S10 (±7 días). Las evaluaciones posteriores del tumor se realizarán cada 8 semanas (±7 días) hasta la semana 50. Una vez finalizadas las 50 semanas de evaluación radiológica, estas evaluaciones se llevarán a cabo cada 12 semanas (±7 días). Se realizarán estudios de imagen adicionales de posibles focos de enfermedad siempre que se sospeche progresión radiológica de la enfermedad (PE). |
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E.5.2 | Secondary end point(s) |
Duration of OS (overall survival) |
Duracion de La supervivencia global (SG) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Overall survival (OS) will continue to be assessed every 12 weeks (± 14 days) after the second post-treatment follow-up visit (FU-2), which occurs 100 (±14) days after discontinuation of study treatment. Subjects will be followed until death or Sponsor decision to no longer collect these data |
La supervivencia global (SG) se evaluará cada 12 semanas (±14 días) después de la visita de SEG-2, que tendrá lugar 100 (±14) días después de la fecha en que se tome la decisión de suspender el tratamiento del estudio. Los pacientes serán objeto de seguimiento hasta que fallezcan o hasta que el promotor tome la decisión de dejar de recopilar estos datos |
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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 | 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 |
immunogenicity, biomarkers |
inmunogenicidad, biomarcadores |
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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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | 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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 |
Brazil |
Canada |
Chile |
Hong Kong |
Israel |
Mexico |
New Zealand |
Singapore |
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
|
End of trial is defined as the last scheduled visit or scheduled procedure for the last subject (including Maintenance Phase assessments) |
Final del ensayo: El final del ensayo se define como la última visita o procedimiento programado para el último paciente (incluidas las evaluaciones de la fase de mantenimiento). |
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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 | 11 |
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 | 2 |