E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with upper urinary tract transitional cell carcinoma (UTUC) |
Pacientes con carcinoma de celulas de transicion del tracto urinario superior |
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E.1.1.1 | Medical condition in easily understood language |
Patients with invasive upper urinary tract carcinoma |
Pacientes con carcinoma invasivo del tracto urinario superior |
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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 | 10064467 |
E.1.2 | Term | Urothelial carcinoma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the proportion of UTUC patients randomized to neo or adjuvant chemotherapy that is actually able to start and finalize three courses of planned chemotherapy |
Determinar la proporcion de pacientes randomizados para tratamiento con quimioterapia neoadjuvante o adjuvante que completan los 3 ciclos de tratamiento planificados |
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E.2.2 | Secondary objectives of the trial |
To assess 1- and 2-year Disease Free Survival (DFS), Overall Survival (OS) and Cancer-Specific Survival (CSS) |
Determinar Supervivencia libre de enfermedad, Supervivencia Global y Supervivencia hasta progresion a 1 y 2 años |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• written informed consent • Age ≥ 18 years. • Histological and radiological defined UTUC: Histologically-confirmed diagnosis of predominantly urothelial carcinoma of the upper urinary tract •Patients with UTUC cT2-pT4 cN0-N1 M0 (TNM classification) •Women of childbearing potential must have a negative serum pregnancy test within 14 days of first dose of study treatment and agree to use effective contraception during the study and for 14 days following the last dose of study treatment. •Patients without bladder cancer or with concomitant non muscle invasive bladder cancer •Adequate organ system function defined by Hematological results: Absolute neutrophil count (ANC) 1.5 X 109/L; Haemoglobin 5.6 mmol/L ( ≥9.02g/dL); Platelets 100 X 109/L; Prothrombin time (PT) or international normalized ratio (INR)b 1.2 X ULN; Activated partial thromboplastin time (aPTT)1.2 X ULN. Hepatic: Total bilirubin1.5 X ULN; Alanine amino transferase (ALT) and Aspartate aminotransferase (AST) 2.5 X ULN. Renal: GRF < or 55 ml/min: Electrolytes: potassium, magnesium and calcium: within normal limits. •CT scan of the chest, abdomen and pelvis and bone scan without evidence of distant metastasis |
Consentimiento informado firmado ≥ 18 años Prueba histológica y radiológica de Carcinoma urotelial del tracto urinario superior (UTUC por sus siglas en inglés). Diagnostico confirmado de carcinoma urotelial del tracto urinario superior. Pacientes UTUC cT2-pT4 cN0-N1 M0 (clasificación TNM) Las mujeres aptas para concebir deber mostrar un test negativo antes de 14 días de la fecha de la primera dosis del tratamiento y estar de acuerdo con el uso de un tratamiento anticonceptivo eficaz durante el periodo del estudio y hasta 14 días después de finalizar la última dosis del tratamiento. Pacientes sin cáncer de vejiga o con cáncer de vejiga concomitante no invasivo Buena función de los organos definida de la siguiente manera: Hematologia: Recuento absoluto de neutrofilos (ANC) 1.5 X 109/L; Hemoglobina 5.6 mmol/L ( ≥9.02g/dL); Plaquetas 100 X 109/L; Tiempo de Protrombina (PT) o ratio internacional normalizado (INR)b 1.2 X ULN; Tiempo de activación parcial de tromboplastina (aPTT)1.2 X ULN. Función hepática: Bilirrubina Total 1.5 X ULN; Alanina amino transferasa (ALT) and Aspartato aminotransferasa (AST) 2.5 X ULN. Renal: GRF < or 55 ml/min: Electrolitos: potasio, magnesio y calcio dentro de los límites normales. Tomografía computarizada del tórax, abdomen y pelvis y escáner óseo sin evidencia de metástasis |
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E.4 | Principal exclusion criteria |
•Histology of pure adenocarcinoma, pure squamous cell carcinoma, sarcomatoid or predominant small cell carcinoma. •History of cardiovascular conditions within the past 6 months. •Incidentally found asymptomatic pulmonary embolism (PE) or recent deep vein thrombosis (DVT) is not an exclusion criteria but requires anticoagulation treatment. •Subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation. •Any major contraindication to a surgical procedure. •Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject’s safety, provision of informed consent, or compliance to study procedures. •Active infection contraindicating chemotherapy (under investigator criteria). •Concomitant diseases that are a formal exclusion to platinum-based chemotherapy (deafness, grade II neuropathy). •Other active neoplasms. Patients with in situ cervical carcinoma, non-melanoma skin cancer or prostate cancer T1 Gleason <7, PSA <10. Patients with past medical history of cancer can be included if diagnosed at least 5 years ago. •Concomitant muscle invasive bladder cancer. •Patients who have been or still are on methotrexate treatment. |
Histología de adenocarcinoma puro, carcinoma puro de células escamosas, sarcomatoide o carcinoma predominante de células pequeñas Historia de alguna condición cardiovascular en los últimos 6 meses. Embolismo pulmonar asintomático accidentalmente presente o trombosis venosa profunda reciente no son un criterio de exclusión pero deben ser tratados con anticoagulantes Cualquier contraindicación del tratamiento quirúrgico Cualquier condición preexistente grave o inestable, psiquiátrica o de cualquier otro tipo, que pueda interferir en la seguridad del paciente, obtención del consentimiento informado o cumplimiento con el tratamiento y condiciones del estudio Cualquier infección contraindicada con el tratamiento con quimioterapia (según criterio del investigador) Enfermedades concomitantes que interfieren con el tratamiento con medicación basada en platino (sordera, neuropatía en grado II) Otros neoplasmas activos. Pacientes con carcinoma cervical in situ, cáncer de piel no melanoma o de próstata T1 Gleason <7, PSA <10. Los pacientes con historial de cáncer pueden participar en el ensayo siempre y cuando haya sido diagnosticado hace 5 o más años. Cáncer de vejiga con invasión muscular Pacientes tratados o en tratamiento con metrotexato |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of UTUC patients randomized to neo or adjuvant chemotherapy that is actually able to start and finalize three courses of planned chemotherapy |
Determinar la proporcion de pacientes randomizados para tratamiento con quimioterapia neoadjuvante o adjuvante que completan los 3 ciclos de tratamiento planificados |
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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) |
1- and 2-year Disease Free Survival (DFS), Overall Survival (OS) and Cancer-Specific Survival (CSS) |
Determinar Supervivencia libre de enfermedad, Supervivencia Global y Supervivencia hasta progresion a 1 y 2 años |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1,2 and 5 years |
1,2,y 5 años |
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Explore feasibility of UTUC treatments based on real world data |
Explorar viabilidad del tratamiento de carcinoma urotelial del tracto urinario superior en base a los datos de practica clinica habitual |
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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) | 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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Neo-adjuvant vesus adjuvant treatment is compared |
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E.8.2.4 | Number of treatment arms in the trial | 5 |
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
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 | 5 |