Clinical Trials Register

Summary
EudraCT Number:	2015-002240-14
Sponsor's Protocol Code Number:	TARIBO
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-11-04
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2015-002240-14

A.3

Full title of the trial

Targeted Therapy with or without Nephrectomy in Metastatic Renal Cell Carcinoma: Liquid Biopsy for Biomarkers Discovery

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Targeted therapy with or without nephrectomy in metastatic renal cell carcinoma

Terapie target con o senza nefrectomia nel carcinoma renale metastatico

A.3.2

Name or abbreviated title of the trial where available

TARIBO

A.4.1

Sponsor's protocol code number

TARIBO

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	FONDAZIONE IRCCS "ISTITUTO NAZIONALE DEI TUMORI"
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AIRC
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fondazione Istituto dei Tumori di Milano
B.5.2	Functional name of contact point	Servizio Informazione sulla Sperime
B.5.3	Address:
B.5.3.1	Street Address	Via Venezian 1
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20133
B.5.3.4	Country	Italy
B.5.4	Telephone number	0223904449
B.5.5	Fax number	0223902149
B.5.6	E-mail	elena.verzoni@istitutotumori.mi.it

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	SUTENT - 30 CAPSULE "30 CAPSULE DA 12.5 MG"
D.2.1.1.2	Name of the Marketing Authorisation holder	PFIZER LIMITED
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Sutent
D.3.2	Product code	[SU-011248]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SUNITINIB MALATO
D.3.9.1	CAS number	341031-54-7
D.3.9.2	Current sponsor code	SU011248
D.3.9.3	Other descriptive name	Sunitinib malate
D.3.9.4	EV Substance Code	SUB22366
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	12
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	SUTENT - 30 CAPSULE "30 CAPSULE DA 25 MG"
D.2.1.1.2	Name of the Marketing Authorisation holder	PFIZER LIMITED
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Sutent
D.3.2	Product code	[SU-011248]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SUNITINIB MALATO
D.3.9.1	CAS number	341031-54-7
D.3.9.2	Current sponsor code	SU011248
D.3.9.3	Other descriptive name	Sunitinib malate
D.3.9.4	EV Substance Code	SUB22366
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	SUTENT - 50 MG CAPSULE 30 CAPSULE
D.2.1.1.2	Name of the Marketing Authorisation holder	PFIZER LIMITED
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Sutent
D.3.2	Product code	[SU-011248]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SUNITINIB MALATO
D.3.9.1	CAS number	341031-54-7
D.3.9.2	Current sponsor code	SU011248
D.3.9.3	Other descriptive name	Sunitinib malate
D.3.9.4	EV Substance Code	SUB22366
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	VOTRIENT - 200 MG -COMPRESSA RIVESTITA CON FILM -USO ORALE-FLACONE (HDPE) 30 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	GLAXO GROUP LIMITED
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Votrient
D.3.2	Product code	[GW786034]
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PAZOPANIB
D.3.9.1	CAS number	444731-52-6
D.3.9.2	Current sponsor code	GW786034
D.3.9.3	Other descriptive name	Pazopanib
D.3.9.4	EV Substance Code	SUB29175
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 5
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	VOTRIENT - 400 MG -COMPRESSA RIVESTITA CON FILM -USO ORALE-FLACONE (HDPE) 30 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	GLAXO GROUP LIMITED
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Votrient
D.3.2	Product code	[GW786034]
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PAZOPANIB
D.3.9.1	CAS number	444731-52-6
D.3.9.2	Current sponsor code	GW786034
D.3.9.3	Other descriptive name	Pazopanib
D.3.9.4	EV Substance Code	SUB29175
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	400
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients affected by non treated metastatic renal cell carcinoma

Pazienti affetti da carcinoma renale metastatico non pre-trattato

E.1.1.1

Medical condition in easily understood language

Patient with metastatic renal cancer

Pazienti con cancro renale metastatico

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	21.0
E.1.2	Level	PT
E.1.2	Classification code	10073251
E.1.2	Term	Clear cell renal cell carcinoma
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare clinical benefit, as measured by OS, provided by CN followed by TKIs vs upfront TKIs in subjects with mRCC

Valutare il beneficio clinico, valutato in termini di Sopravvivenza Globale (OS) della nefrectomia citoriduttiva seguita da trattamento con TKIs verso trattamento sistemico upfront con TKIs in pazienti affetti da carcinoma renale metastatico alla diagnosi

E.2.2

Secondary objectives of the trial

- To compare clinical benefit, as measured by PFS and response rate (RR) provided by CN followed by TKIs vs upfront TKIs
- Safety

- Valutare il beneficio clinico, valutato in termini di sopravvivenza libera da progressione (PFS) e percentuale di risposta (RR) della nefrectomia citoriduttiva seguita da trattamento con TKIs verso trattamento sistemico upfront con TKIs
- Valutare il profilo di sicurezza di entrambi i bracci di trattamento

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Other types of substudies
Specify title, date and version of each substudy with relative objectives: Evaluation of predictive role of CTCs count and ctDNA at baseline, pre- and post-operatively (in patients undergoing CN), 24 weeks after randomization and at the time of PD.
Version 1.0 dated 9 December 2014.
Objective: evaluation of the predictive factors of the response to treatment.

Altre tipologie di sottostudi
specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Valutare il ruolo predittivo della conta dell CTCs e del ctDNA al baseline, pre e post chirurgia (per i pazienti che riceveranno nefrectomia citoriduttiva), 24 settimane dopo la randomizzazione e alla progressione.
Versione 1.0 del 9 dicembre 2014.
Obiettivo: valutazione dei fattori predittivi di risposta al trattamento.

E.3

Principal inclusion criteria

• Age > 18 and < 75 years
• Written informed consent
• ECOG Performance Status 0-1
• Favorable or intermediate MSKCC or Heng risk score
• Biopsy (primary tumour or metastases) confirming the diagnosis of predominantly clear cell RCC
• Resectable asymptomatic in situ primary (asymptomatic primary is defined as the absence of symptoms which can be exclusively assigned to the primary tumor such as flank pain and/or gross hematuria necessitating blood transfusion.)
• Tumour suitable to nephrectomy in the opinion of the urologist. Patients with Inferior vena cava thrombosis can be included
• Documented metastatic disease (CT scan or MRI)
• Life expectancy > or = 24 weeks
• Up to three different metastatic sites
• = 3 metastatic lesions
• Platelets = 100,000/ml
• Haemoglobin = 9.0 g/dl
• neutrophils >1,500/mm3
• Bilirubin < or = 2 mg/dl, except for patients affected by Gilbert’s syndrome
• AST and ALT < or = 2.5 times the UNL
• Serum albumin = the LNL
• Patients of childbearing age should use contraceptive methods during the study

• Età = 18 anni e = 75 anni
• Consenso informato scritto
• ECOG Performance Status di 0 o 1
• Categoria prognostica secondo MSKCC o Heng: buona o intermedia
• Biopsia (sul tumore primitivo o un sito metastatico) che confermi la diagnosi di carcinoma renale con predominanza di cellule chiare
• Tumore primitivo in sede asintomatico (definito dall’assenza di sintomi che possono essere riferibili unicamente ad esso-quali dolore al fianco e /o ematuria tale da rendere necessaria emotrasfusione
• Tumore primitivo tecnicamente resecabile nell’opinione del chirurgo urologo. Pazienti con trombosi della vena cava inferiore possono essere inclusi.
• Malattia metastatica misurabile (TAC o RMN)
• Aspettativa di vita di almeno 24 settimane.
• Massimo 3 siti metastatici
• = 3 lesioni metastatiche
• Adeguata funzionalità midollare epatica e renale come dimostrato dai parametri ematici eseguiti alla visita di screening e che devono essere:
- Emoglobina = 9.0 g/dl
- Conta dei neutrofili (ANC) >1,500/mm3
- Conta Piastrinica = 100,000/ml
- Bilirubina totale = 2 mg/dl eccetto che pazienti affetti da documentata sindrome di Gilbert
- ALT e AST = 2.5 x il limite superiore di normalità,
- Albumina sierica = limite inferiore di normalità

• 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.

E.4

Principal exclusion criteria

• Prior surgery or systemic treatment for mRCC
• Bilateral RCC
• Brain and liver metastases
• Non-clear-cell histology
• Poor prognosis as defined by MSKCC or Heng criteria
• Documented widespread disease (> or =4 metastatic organ sites)
• Oligometastatic disease suitable of metastasectomy (<3 lesions confined at one organ site)
• Symptomatic primary tumour at presentation
• High surgical risk in the opinion of the urologist
• Patients with > 3 of the following surgical risk factors are not eligible:
-Serum albumin CTCAE v 4.0 grade 2 or worse
-Serum LDH > 1.5 times upper limit of normal
-Symptoms at presentation due to metastases
-Clinical stage T4 disease

- History of malabsorption syndrome
• Pregnant or breastfeeding women
• Concomitant cardiac disorders: cardiac failure NYHA> 2; Acute coronary syndrome or myocardial infarction or severe or unstable angina within the last 6 months as well as uncontrolled hypertension (sistolic>160, diastolic>90), arrhytmia requiring treatment (except for beta blockers or digossin)
• Uncontrolled diabetes
• Deep phlebitis not treated with LMWH or arterial thrombosis within the last 6 months
• HIV infection
• Active infections (> Grade 2 NCI-CTC v.3.0)
• Patients with active bleeding or with pathological conditions increasing the risk of bleeding
• Other cancer within the previous 5 years (except for in situ skin carcinoma, superficial bladder Ta, Tis, T1 and carcinoma of the cervix or every cancer with curative treatment within 5 years)

• Precedente trattamento medico o chirurgico per carcinoma renale metastatico
• Tumore renale bilaterale
• Metastasi cerebrali o epatiche
• Istologia non a cellule chiare
• Categoria prognostica secondo MSKCC o Heng: poor
• Malattia metastatica diffusa (= 4 organi metastatici)
• Malattia oligometastatica suscettibile di metastasectomia (< 3 lesioni)
• Tumore primitivo sintomatico alla diagnosi (presenza di dolore al fianco o ematuria macroscopica condizionante anemizzazione che richieda emotrasfusione)
• Elevato rischio chirurgico in opinione del chirurgo urologo
• Pazienti con più di 3 dei seguenti fattori di rischio chirurgico con sono eleggibili:
- Ipolbuminemia (CTCAE v.4.0 grado 2 o superiore)
- LDH > 1.5 volte il limite superiore di normalità
- Sintomi alla presentazione a causa delle localizzazioni metastatiche
- Stadio clinico cT4

• Storia di malassorbimento o impossibilità di assumere compresse
• Donne incinta o in allattamento
• 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 bloccanti o digossina sono permessi) o ipertensione non controllata (sistolica = 160 mmHg e/o diastolica = 90 mmHg).
• Diabete scompensato
• Trombosi venosa profonda non trattata con eparina a basso peso molecolare (nei sei mesi precedenti)
• Infezione da HIV
• Infezioni in fase attiva (> grado 2 NCI-CTC versione 3.0)
• Pazienti con sanguinamento attivo o con condizioni patologiche che aumentino il rischio di sanguinamento
• Precedente o concomitante diagnosi di cancro distinto per il sito primario con l’eccezione del carcinoma cervicale in situ, il basalioma trattato, il tumore superficiale della vescica [Ta, Tis & T1] o ogni tumore trattato in maniera curativa in un periodo di tempo superiore a 5 anni precedenti lo studio.

E.5 End points

E.5.1

Primary end point(s)

Overall Survival (OS)

Sopravvivenza complessiva (OS)

E.5.1.1

Timepoint(s) of evaluation of this end point

time interval between the randomization and the time of death for any cause

tempo dalla randomizzazione al decesso del paziente per qualsiasi causa

E.5.2

Secondary end point(s)

Progression-free survival; Overall response rate

Sopravvivenza libera da progressione; Percentuale di risposta globale

E.5.2.1

Timepoint(s) of evaluation of this end point

From randomization to disease progression or death of the subject; From randomization to disease progression or death of the subject

Dalla randomizzazione fino alla progressione di malattia o decesso del paziente; Dalla randomizzazione fino alla progressione di malattia o decesso del paziente

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Predictive factors of response

Fattori predittivi di risposta

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

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

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

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

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

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

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

180

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

270

F.4.2

For a multinational trial

F.4.2.1

In the EEA

270

F.4.2.2

In the whole clinical trial

270

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

The therapy will be continued until disease progression or unacceptable toxicity. Then patients will be treated according to the local clinical practice of the site.

La terapia sarà continuata fino a progressione di malattia o tossicità inaccettabile. A seguire i pazienti saranno trattati secondo la pratica clinica locale del centro.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-09-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-07-23

P. End of Trial
P.	End of Trial Status	Completed

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