E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic clear cell renal cancer |
Cancer renal metastásico de células claras. |
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E.1.1.1 | Medical condition in easily understood language |
Renal Cancer |
Cancer de riñón |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038416 |
E.1.2 | Term | Renal clear cell carcinoma |
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 |
Progression-free survival (PFS) |
Supervivencia libre de Progresión (SLP) |
|
E.2.2 | Secondary objectives of the trial |
a)PFS of sequential arm versus PFS of the 2 lines in control arm. b)Objective tumor response rate (ORR) per arm c)Overall Survival (OS) d)Safety Profile |
a)La SLP del grupo consecutivo, en comparación con la SLP de las dos líneas en el grupo control. b)La tasa de respuesta objetiva (TRO) del tumor, por grupo. c) La supervivencia global (SG). d) El perfil de seguridad. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Renal cell carcinoma with a predominant clear cell component confirmed by histology or cytology -Advanced disease: metastatic AND, not suitable for resection -Male or female, aged 18 years or older -ECOG 0 or 1 -Low or intermediate MSKCC prognostic risk score -Target and/or non-target lesions according to RECIST 1.1 -Expected survival of at least 3 months. -No prior systemic treatment. -Adequate bone marrow function -Adequate liver function -Adequate renal function as shown by serum creatinine < 1.5 x ULN -Left ventricular ejection fraction >55% on gated cardiac blood pool scan, or normal left ventricular function and fractional shortening on echocardiogram (according to institutional limits). -Systolic blood pressure <140mmHg and diastolic blood pressure <90mmHg (it is acceptable to initiate antihypertensive treatment prior to registration to achieve these goals). -Able to commence treatment within 7 days of registration. -Willing and able to comply with follow-up and all other protocol requirements. -Written informed consent |
-Adenocarcinoma de células renales, con un componente predominante de células claras, confirmado mediante la histología o la citología. -Enfermedad avanzada: metastásica Y no adecuada para la extirpación. -Hombre o mujer, a partir de 18 años. -ECOG de 0 o 1 -Puntuación baja o intermedia del riesgo pronóstico según el MSKCC -Lesiones afectadas o no afectadas, según RECIST 1.1 -Supervivencia esperada de por lo menos tres meses. -Ausencia de tratamiento previo por vía sistémica. -Función adecuada de la médula ósea -Función hepática adecuada, -Función renal adecuada, demostrada por una creatinina sérica < 1,5 x LSN. -Fracción de eyección del ventrículo izquierdo > 55% en la escanografía de la mezcla de sangre cardíaca sincronizada, o función normal del ventrículo izquierdo y acortamiento fraccional en la ecocardiografía (según los límites del centro). -Presión arterial sistólica < 140 mm Hg y presión arterial diastólica < 90 mm Hg (es aceptable comenzar un tratamiento antihipertensivo antes del registro para alcanzar estos objetivos). -Capaz de comenzar el tratamiento en un plazo de siete días después del registro. -Deseoso y capaz de cumplir con los controles y todos los demás requisitos del protocolo. -Consentimiento informado por escrito. |
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E.4 | Principal exclusion criteria |
-Prior treatment with VEGF-targeting agents or multi-kinase inhibitors or mTOR-targeting agents -Active central nervous system metastases. -Other malignancy diagnosed within the last 5 years, except the following if adequately treated: superficial squamous cell carcinoma or basal cell carcinoma of skin, superficial bladder cancer (T1 and G1 or T1 and G2), stage 1 cervical cancer. -Treatment with an investigational agent in the last 4 weeks. -Known to be HIV positive -Evidence of chronic hepatitis due to HBV or HCV -Clinically significant heart disease -History of hypertension requiring hospitalization. -Other serious illnesses, e.g. active infection requiring antibiotics, bleeding disorders. -Immunotherapy or chemotherapy in the last 4 weeks -Major surgery in the last 4 weeks, or planned in the next 6 weeks. -Radiation therapy in the last 2 weeks, or planned in the next 6 weeks -grade 3 or worse hemorrhage in last 4 weeks -Any of the following in the last year: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism -Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication -Ongoing cardiac dysrhythmias grade >2, atrial fibrillation of any grade, or prolongation of the corrected QT interval (QTc) to >450 msec for males or >470 msec for females -Uncontrolled diabetes as defined by fasting serum glucose >1.5 X ULN -Pregnancy -Known allergy or hypersensitivity to everolimus, sunitinib or iodine -Medical or psychiatric condition that compromises the patients ability to give informed consent |
-Tratamiento anterior con fármacos dirigidos al VEGF o inhibidores de la multicinasa o fármacos dirigidos a la mTOR -Metástasis activas en el sistema nervioso central. -Otra neoplasia maligna diagnosticada en los cinco últimos años, excepto las siguientes, si reciben un tratamiento suficiente: carcinoma espinocelular superficial o carcinoma basocelular de la piel, cáncer superficial de vejiga (Y1 y G1, o T1 y G2), cáncer cervical en estadio 1. -Tratamiento con un fármaco experimental en las cuatro últimas semanas. -VIH positivo -Evidencia de hepatitis crónica causada por el VHB o VHC -Cardiopatía clínicamente significativa -Antecedentes de hipertensión que ha precisado hospitalización. -Otras enfermedades graves, p. ej., infección activa que requiere antibióticos, trastornos hemorrágicos. -Inmunoterapia o quimioterapia en las cuatro últimas semanas -Cirugía mayor en las cuatro últimas semanas o planificada para las siguientes seis semanas. -Radioterapia en las dos últimas semanas o planificada para las siguientes seis semanas. -Hemorragia de grado 3 o peor, en las cuatro últimas semanas. -Cualquiera de las siguientes circunstancias en el último año: infarto de miocardio, angina grave o inestable, injerto de derivación coronaria o de arteria periférica, insuficiencia cardíaca congestiva sintomática, accidente cerebrovascular o ataque isquémico transitorio, o embolia pulmonar. -Anomalía tiroidea preexistente, con función tiroidea que no se puede mantener dentro de los límites normales con la medicación. -Disritmias cardíacas en curso, de grado > 2, según los NCI CTCAE, versión 4.0, fibrilación auricular de cualquier grado, o prolongación del intervalo QT corregido (QTc) a > 450 mseg para los varones o > 470 mseg para las mujeres. -Diabetes no controlada, definida por una glucosa sérica en ayunas > 1,5 x LSN. -Embarazo. -Alergia o hipersensibilidad comprobada al everolimus, al sunitinib o al yodo. -Afección médica o psiquiátrica que afecte a la capacidad del paciente para otorgar su consentimiento informado. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
a) Progression b) Partial and Complete responses c) Survival d) Adverse events |
a) Progresión b) Respuestas parciales y completas c) Supervivencia d) Acontecimientos Adversos |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | No |
E.6.13 | Others | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Los mismos productos en régimen estandar |
The same medicinal products under standard regimen |
|
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 | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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 |
Ultima Visita del Ultimo 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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |