E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | |
E.1.1.1 | Medical condition in easily understood language |
metastatic renal cell carcinoma |
tumore del rene 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 | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067946 |
E.1.2 | Term | Renal cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of sorafenib (PFS) as second line of treatment in patients treated with pazopanib for mRCC. |
Valutare l'efficacia di sorafenib come trattamento di seconda linea in pazienti già trattati con pazopanib |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the safety of sorafenib in patients previously treated with pazopanib
• To evaluate the Overall Survival
• To evaluate the Quality of Life through specific questionnaires (FKSI-19; EORTC QLQ-C30).
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sicurezza, sopravvivenza globale e qualità della vita |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age ≥ 18 years
• Patients with hystological diagnosis of Renal Cell Carcinoma (RCC)
• Measurable disease
• ECOG Performance Status of 0 or 1
• Life expectancy of at least 12 weeks.
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:
- Hemoglobin 10.0 g/dl
- Absolute neutrophil count (ANC) >1,500/mm3
- Platelet count 100,000/ml
- Total bilirubin ≤ 1.5 times the upper limit of normal
- ALT and AST ≤ 2.5 x upper limit of normal
- Alkaline phosphatase ≤ 4 x ULN
- PT-INR/PTT ≤ 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.] For patients on warfarin, close monitoring of at least weekly evaluations will be performed, until INR is stable based on a measurement at pre-dose, as defined by the local standard of care.
• Prognosis according to Heng: good or intermediate
• Previous treatment with pazopanib
• Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and two weeks after the completion of trial.
• Signed informed consent must be obtained prior to any study specific procedures
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• Età ≥ 18 anni
• Pazienti con diagnosi istologica di carcinoma renale (RCC)
• Malattia metastatica misurabile
• ECOG Performance Status di 0 o 1
• Aspettativa di vita di almeno 12 settimane.
• Adeguata funzionalità midollare epatica e renale come dimostrato dai parametri ematici eseguiti alla visita di screening e che devono essere:
- Emoglobina 10.0 g/dl
- Conta dei neutrofili (ANC) >1,500/mm3
- Conta Piastrinica 100,000/ml
- Bilirubina totale ≤ 1.5 x il limite superiore di normalità
- ALT e AST ≤ 2.5 x il limite superiore di normalità
- Fosfatasi alcalina ≤ 4 x il limite superiore di normalità
- PT-INR/PTT ≤ 1.5 x il limite superiore di normalità [pazienti in corso di terapia eparinica o con coumadin possono partecipare allo studio se questi parametri non erano alterati prima dell’inizio della terapia anticoagulante] Per i pazienti in trattamento con farfari un monitoraggio settimane dell’INR è raccomandato fino a stabilizzazione dei valori.
• Categoria prognostica secondo Heng: buona o intermedia
• Precedente trattamento con pazopanib
• Le donne in età fertile devono avere un test di gravidanza negative nei 7 giorni precedenti l’inizio della terapia. Sia uomini che donne in età fertile arruolati nel seguente studio devono adottare adeguati sistemi di protezione durante il corso del trattamento e per le due settimane successive all’interruzione.
• Il consenso informato scritto deve essere ottenuto prima di ogni procedura relative allo studio.
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E.4 | Principal exclusion criteria |
• First line treatment for metastatic RCC other than pazopanib.
• History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 mo prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension (>= 160 mmHg systolic and/or 90 mmHg diastolic).
• History of HIV infection
• Active clinically serious infections (> grade 2 NCI-CTC version 3.0)
• Brain or meningeal metastases
• Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
• History of organ allograft
• Patients with evidence or history of bleeding diasthesis
• Patients undergoing renal dialisis
• History of other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding giving reasonable suspicion of a disease condition that contraindicates use of an investigational drug or patient at high risk from treatment complications
• Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry.
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• Prima linea di trattamento diversa da pazopanib.
• Storia di patologie cardiache: insufficienza cardiaca congestizia classe NYHA > 2; Coronaropatia in fase attiva (IMA nei sei mesi precedente la terapia); aritmia richiedente specifica terapia (beta beta bloccanti o digossina sono permessi) o ipertensione incontrollata (sistolica ≥ 160 mmHg e/o diastolica ≥ 90 mmHg).
• Infezione da HIV
• Infezioni in fase attiva (> grado 2 NCI-CTC versione 3.0)
• Presenza di metastasi encefaliche o meningee
• Paziente con storia di crisi epilettiche che richiedono terapie specifiche (come steroidi e/o antiepilettici)
• Storia di trapianto d’organo
• Pazienti con evidenza di emorragie o diastasi
• Pazienti in corso di dialisi
• Storia di malattie come disfunzioni metaboliche , anomalie all’esame fisico o laboratoristici che possano far sospettare per la presenza di condizioni di malattia sottostante che possano controindicare l’uso del farmaco oggetto di studio o che possano mettere il paziente a rischio di tossicità.
• Precedente o concomitante diagnosi di cancro distinto per il sito primario o per la forma istologica con l’eccezione del carcinoma cervicale in situ, il carcinoma a cellule basale trattato, il tumore superficiale della vescica [Ta, Tis & T1] o ogni tumore trattato in maniera curativa in un periodo di tempo superiore a 3 anni precedenti lo studio.
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the efficacy of sorafenib (PFS) as second line of treatment in patients treated with pazopanib for mRCC. |
Valutazione dell'efficacia di sorafenib come trattamento di seconda linea in pazienti con carcinoma renale metastatico trattati con pazopanib |
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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) |
safety, Overall survival and quality of life |
sicurezza, sopravvivenza globale e qualità della vita |
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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 | No |
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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
a braccio singolo |
single arm |
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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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 10 |
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 | 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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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |