E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced and/or metastatic renal carcinoma. |
Carcinoma a cellule renali in stadio localmente avanzato e/o metastatico. |
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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 | PT |
E.1.2 | Classification code | 10061482 |
E.1.2 | Term | Renal neoplasm |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate and compare progression free survival (PFS) of patients treated with pazopanib to those treated with placebo. |
Valutare e confrontare la sopravvivenza libera da malattia (PFS) dei pazienti trattati con Pazopanib e di quelli trattati con placebo. |
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E.2.2 | Secondary objectives of the trial |
The principal secondary objective is: To compare overall survival (OS) of patients treated with pazopanib to those treated with placebo. Other secondary objectives are: To compare overall response rate [ORR = complete response (CR) + partial response (PR)] in patients treated with pazopanib to those treated with placebo. To compare the rate of CR + PR + 6-months stable disease (SD) in patients treated with pazopanib to those treated with placebo. To assess the incidence, severity and causality of all adverse events (AE), serious adverse events (SAEs) and other safety parameters in patients treated with pazopanib and placebo. |
Il principale obiettivo secondario e`: Confrontare la sopravvivenza globale (OS) dei pazienti trattati con Pazopanib e di quelli trattati con placebo.Altri obiettivi secondari: Confrontare la percentuale di risposta globale [ORR = risposta completa (CR) + risposta parziale (PR)] dei pazienti trattati con Pazopanib e di quelli trattati con placebo. Confrontare la percentuale di CR + PR + malattia stabile (SD) per 6 mesi dei pazienti trattati con Pazopanib e in quelli trattati con placebo. Valutare l'incidenza,la gravita` e la causa di tutti gli eventi avversi (AE),degli eventi avversi gravi (SAE) e di altri parametri di sicurezza nei pazienti trattati con Pazopanib e con placebo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Signed written consent form. 2) Diagnosis of clear cell RCC that is predominantly clear cell histology. 3) Locally advanced and/or metastatic RCC (equivalent to Stage IV RCC according to AJCC staging. 4) Must have measurable disease, i.e. presenting with at least one measurable lesion per RECIST. A measurable lesion is defined as a lesion that can be accurately measured in at least one dimension with the longest diameter >20mm using conventional techniquest, or >10 mm with spiral CT scan. 5) Documented disease progression (based on radiographic imaging) following a first-line cytokine-based systemic treatment for locally advanced or metastatic RCC. The first-line cytokine-based treatment can be interleukin-2 (IL -2) or interferon-alpha (INF-alpha) monotherapy, or IL-2 or INF-alpha in combination with chemotherapy. 6) Male or female >21 years of age. 7) ECOG PS 0 or 1. 8) Adequate baseline organ function as defined in the protocol. 9)At least 4 weeks must have elapsed since the last surgery and 2 weeks must have elapsed since radiotherapy or the last systemic cytokine therapy. 10)Complete recovery from prior surgery, and/or reduction of all AEs to Grade 1 from prior systemic therapy or radiotherapy. |
1)Firma del consenso informato scritto.2)Diagnosi di RCC a cellule chiare con prevalenza di tipo istologico a cellule chiare. 3) RCC localmente avanzato e/o metastatico (equivalente a RCC di Stadio IV secondo la classificazione AJCC). 4) Malattia misurabile, ovvero almeno una lesione misurabile secondo RECIST. Una lesione misurabile e` definita come una lesione con almeno una dimensione misurabile con precisione, con diametro > 20mm con l'uso di tecniche convenzionali o > 10mm con TAC spirale. 5) Progressione documentata della malattia (in base alle immagini radiologiche) in seguito a trattamento sistemico di prima linea con citochine per l'RCC localmente avanzato o metastatico. Il trattamento di prima linea con citochine puo` essere una monoterapia con interleuchina-2 (IL-2) o interferone-alfa (INFalfa); oppure IL-2 o INF-alfa; in combinazione con chemioterapia. 6) Uomo o donna con eta` >= 21 anni. 7)ECOG PS 0 o 1. 8)Funzionalita` organica basale adeguata. 9)Devono essere trascorse almeno 4 settimane dall'ultimo intervento chirurgico e 2 settimane dalla radioterapia o dall'ultima terapia sistemica con citochine. 10)Completo recupero da intervento chirurgico precedente e/o riduzione al Grado 1 di tutti gli AE provocati da terapia sistemica o radioterapia precedenti. |
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E.4 | Principal exclusion criteria |
1)Pregnant or lactating female. 2)History of another malignancy. 3)History or presence of central nervous system (CNS) metastasis or leptomeningeal tumors as documented by CT or MRI scan, analysis of cerebrospinal fluid or neurological exam. 4) Malabsorption syndrome or disease that significantly affects gastrointestinal function, or major resection of the stomach or small bowel that could affect the absorption of pazopanib. 5)Unable to swallow and retain orally administered medication. 6) Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to beginning study treatment. 7)History of human immunodeficiency virus infection. 8) Presence of uncontrolled infection. 9)Corrected QT interval (QTc) prolongation defined as QTc interval > 470 msecs. 10)History of Class III or IV congestive heart failure according to New York Heart Association (NYHA) classification [See Section 14.5 Appendix 5 for description].11)History of any one of the following cardiac conditions within the past 6 months: Cardiac angioplasty or stenting, or Myocardial infarction, or Unstable angina.12)History of cerebrovascular accident within the past 6 months. 13)Poorly controlled hypertension [defined as systolic blood pressure (SBP) of >=140mmHg, or diastolic blood pressure (DBP) of >= 90mmHg]. 14) History of untreated deep venous thrombosis (DVT) within the past 6 months (e.g. a calf vein thrombosis that is not treated). 15)Presence of any non-healing wound, fracture, or ulcer, or presence of symptomatic peripheral vascular disease. 16)Evidence of bleeding diathesis or coagulopathy.17)Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with patient's safety, obtaining informed consent or compliance to the study. 18) Has taken any prohibited medications that are listed in Section 8.2 within 14 days of the first dose of study medication. 19) Current or prior use of an investigational anti-cancer drug within 4 weeks of start of study.20)Prior use of an investigational or licensed drug that targets VEGF or VEGF receptors (eg. bevacizumab, sunitinib, sorafinib, etc). |
1.Donna in gravidanza o allattamento. 2.Storia di un altro tumore maligno. 3.Storia di metastasi al sistema nervoso centrale (SNC) o tumori leptomeningei documentata da TAC o RMN, analisi del liquido cerebrospinale o esame neurologico. 4.Sindrome o malattia da malassorbimento che influisce in modo significativo sulla funzione gastrointestinale, o resezione maggiore dello stomaco o dell'intestino tenue che puo` influire sull'assorbimento di Pazopanib. 5.Incapacita` a deglutire o trattenere farmaci somministrati oralmente. 6.Ulcera peptica attiva, malattia infiammatoria intestinale, colite ulcerosa o altra patologia gastrointestinale con accresciuto rischio di perforazione; storia di fistola addominale, perforazione gastrointestinale o ascesso intra-addominale nelle 4 settimane precedenti l'inizio del trattamento in studio. 7.Storia di infezione da virus dell'immunodeficienza umana. 8.Infezione incontrollata. 9.Prolungamento dell'intervallo QT corretto (QTc) definito come intervallo QTc > 470 msec. 10.Storia di insufficienza cardiaca congestizia di Classe III o IV secondo la classificazione della New York Heart Association (NYHA). 11.Storia di una delle seguenti condizioni cardiache nei 6 mesi che precedono l'ingresso in studio: Angioplastica o stenting cardiaco, oppure Infarto miocardico, oppure Angina instabile. 12.Storia di incidente cerebrovascolare nei 6 mesi precedenti. 13.Ipertensione mal controllata [definita come pressione sanguigna sistolica (SBP) ³140 mmHg, o pressione sanguigna diastolica (DBP) ³ 90 mmHg].14.Storia di trombosi venosa profonda (TVP) non trattata nei 6 mesi precedenti (es. TVP del polpaccio non trattata). 15.Presenza di ferita, frattura o lesione ulcerativa di difficile guarigione, o presenza di malattia vascolare periferica sintomatica. 16.Evidenze di diatesi emorragica o coagulopatia. 17.Condizione medica, psichiatrica o di altro genere grave e/o instabile preesistente che potrebbe interferire con la sicurezza del/la paziente, l'ottenimento del consenso informato o la compliance. 8.Assunzione di farmaci non consentiti, elencati nel Capitolo 8.2 nei 14 giorni precedenti la prima dose del farmaco in studio. 19.Uso corrente o precedente di un farmaco antitumorale in fase sperimentale nelle 4 settimane precedenti l'inizio dello studio.20.Uso precedente di un farmaco sperimentale o autorizzato che ha come target il VEGF o i recettori di VEGF (es. bevacizumab, sutinib, sorafinib, ecc.). |
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E.5 End points |
E.5.1 | Primary end point(s) |
PFS defined as the interval between the date of randomization and the earliest date of disease progression (as defined by the independent reviewer) or death due to any cause. |
La PFS definita come l'intervallo tra la data di randomizzazione e la data della prima rilevazione di progressione della malattia (definita dal revisore indipendente) o il decesso per qualsiasi causa. |
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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 | No |
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 | 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) | 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) | No |
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 | 8 |
E.8.5 | The trial involves multiple Member States | No |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 44 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 44 |
E.8.9.2 | In all countries concerned by the trial days | 0 |