Clinical Trials Register

Summary
EudraCT Number:	2011-001790-41
Sponsor's Protocol Code Number:	AB11002
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Suspended by CA
Date on which this record was first entered in the EudraCT database:	2014-07-07
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2011-001790-41

A.3

Full title of the trial

A prospective, multicenter, randomised, open-label, active-controlled, two-parallel groups, phase 3 study to compare the efficacy and safety of masitinib to sunitinib in patients with gastrointestinal stromal tumor after progression with imatinib

Studio prospettico, multicentrico, randomizzato, in aperto, con controllo attivo, a due gruppi paralleli, di fase III per confrontare l'efficacia e la sicurezza di masitinib versus sunitinib in pazienti affetti da tumori stromali gastrointestinali in progressione dopo trattamento con imatinib

A.3.1

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

A.4.1

Sponsor's protocol code number

AB11002

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	AB Science
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AB Science
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AB Science
B.5.2	Functional name of contact point	Catherine LEGER
B.5.3	Address:
B.5.3.1	Street Address	3, avenue George V
B.5.3.2	Town/ city	Paris
B.5.3.3	Post code	75008
B.5.3.4	Country	France
B.5.4	Telephone number	+33147 20 66 76
B.5.5	Fax number	+33147 20 24 11
B.5.6	E-mail	catherine.leger@ab-science.com

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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	ORPHA208427
D.3 Description of the IMP
D.3.1	Product name	masitinib
D.3.2	Product code	AB1010
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	Masitinib Mesylate
D.3.9.1	CAS number	790299-79-5
D.3.9.2	Current sponsor code	AB1010
D.3.9.3	Other descriptive name	MASITINIB MESYLATE
D.3.9.4	EV Substance Code	SUB126308
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	238
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	Comparator
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
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Buccal use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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

Gastrointestinal stromal tumor after progression with imatinib

Tumori stromali gastrointestinali in progressione dopo trattamento con imatinib

E.1.1.1

Medical condition in easily understood language

Cancer of gastrointestinal tract

Cancro del tratto gastrointestinale

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	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10062427
E.1.2	Term	Gastrointestinal stromal tumor
E.1.2	System Organ Class	100000004864

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 efficacy of masitinib at 12 mg/kg/day to sunitinib at 50
mg/day in treatment of patients with gastro-intestinal stromal tumor
after progression with imatinib

Comparare l’efficacia di masitinib 12 mg/kg/die versus sunitinib 50 mg/die nel trattamento di pazienti con tumore stromale gastrointestinale in progressione dopo trattamento con imatinib

E.2.2

Secondary objectives of the trial

To compare safety and quality of life of masitinib at 12 mg/kg/day to sunitinib at 50 mg/day in treatment of patients with gastro-intestinal stromal tumor after progression with imatinib

Comparare la sicurezza e la qualità di vita di masitinib 12 mg/kg/die versus sunitinib 50 mg/die nel trattamento di pazienti con tumore stromale gastrointestinale in progressione dopo trattamento con imatinib

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

PharmacoKinetic (PK) study
A Pharmacokinetics study, in up to 12 patients enrolled in the masitinib group, to evaluate PK parameters of masitinib in GIST patients will be conducted. All samples will be centrally analysed in the Pharmacology Laboratory, Centre René Huguenin, Saint-Cloud, France.
Genetic study
The correlation of expression/mutation of c-kit and PDGFR with primary and secondary endpoints will be assessed.
QT/QTc Study
The impact of masitinib on the QT/QTc in up to 20 patients will be assessed at baseline and at week 4.

Studio di farmacocinetica (PK)
Sarà condotto uno studio di farmacocinetica, su un massimo di 12 pazienti arruolati nel gruppo che ha assunto masitinib, al fine di valutare i parametri di PK di masitinib nei pazienti affetti da GIST. Tutti i campioni saranno analizzati a livello centrale presso il laboratorio di farmacologia del Centre René Huguenin, Saint-Cloud, Francia.
Studio di genetica
Sarà valutata la correlazione fra l'espressione/la mutazione di c-kit e PDGFR, e gli endpoint primari e secondari.
Studio su QT/QTc
L'impatto di masitinib su QT/QTc in un massimo di 20 pazienti sarà valutato al basale e alla settimana 4.

E.3

Principal inclusion criteria

1. Patient with histological proven metastatic GIST or non-operable locally advanced GIST
2. Patient with measurable tumor lesions with longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm with spiral CT scan according to RECIST 1.1
3. Patient with C-kit (CD117) positive tumour detected immuno-histochemically
4. Patient after at least one progression with imatinib at at a dose up to 800mg. Progression is defined as a RECIST 1.1 and/or CHOI disease progression while receiving imatinib treatment.
5. Patient with ECOG ≤ 2
6. Patient with adequate organ functions:
• Absolute neutrophils count (ANC) ≥ 1.5 x 109/L
• Haemoglobin ≥ 10 g/dL
• Platelets (PTL) ≥ 75 x 109/L
• AST/ALT ≤ 3x ULN (≤ 5 x ULN in case of liver metastases)
• Gamma GT ≤ 2.5 x ULN (≤ 5 x ULN in case of liver metastases)
• Bilirubin ≤ 1.5x ULN (≤ 3xULN in case of liver metastases)
• Normal Creatinine or if abnormal creatinine, creatinine clearance ≥ 50 mL/min (Cockcroft and Gault formula)
• Albumin > 1 x LLN
• Proteinuria < 30 mg/mL (1+) on the dipstick. If proteinuria is ≥ 1+ on the dipstick, 24 hours proteinuria must be < 1.5g/24 hours
7. Patient with life expectancy > 6 months
8. Male or female patient, age >18 years
9. Patient BMI > 18 kg/m² and weight > 40 kg
10. Male and female patient of child bearing potential must agree to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake. Female paitent of child bearing potential must have a negative pregnancy test at screening and baseline.
11. Patient able and willing to comply with study procedures as per protocol
12. Patient able to understand, sign, and date the written informed consent form at screening visit prior to any protocol-specific procedures
13. Patient able to understand the patient card and to follow the patient card procedures in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity, during the first 2 months of treatment
14. Patient covered by insurance reimbursing sunitinib

1. Pazienti con GIST metastatico dimostrato istologicamente o con GIST localmente avanzato non operabile
2. Pazienti con lesioni tumorali misurabili col diametro più lungo ≥ 20 mm utilizzando tecniche convenzionali o ≥ 10 mm con TC spirale secondo RECIST 1.1
3. Pazienti con tumore C-kit (CD117) positivo rilevato immuno-istochimicamente
4. Paziente dopo almeno una progressione con imatinib a una dose fino a 800 mg. La progressione è definita come un RECIST 1.1 e / o progressione della malattia CHOI durante il trattamento con imatinib.
5. Paziente con ECOG ≤ 2
6. Pazienti con funzionalità d’organo adeguata
• Conta assoluta dei neutrofili (ANC) ≥ 1.5 x 109/L
• Emoglobina ≥ 10 g/dL
• Piastrine (PTL) ≥ 75 x 109/L
• AST/ALT ≤ 3 x ULN (≤ 5 x ULN in caso di metastasi epatiche)
• Gamma GT ≤ 2,5 x ULN (≤5 x ULN in caso di metastasi epatiche)
• Bilirubina ≤ 1.5 x ULN (≤ 3 x ULN in caso di metastasi epatiche)
• Creatinina normale o se anormale, clearance della creatinina ≥ 50 mL/min (Cockcroft and Gault formula)
• Albumina ≥ 1 x LLN
• Proteinuria < 30 mg/mL (1+) sul dipstick. Se la proteinuria è ≥ 1+ sul dipstick, la proteinuria di 24 ore deve essere < 1.5g/24 ore
7. Pazienti con aspettativa di vita > 6 mesi
8. Pazienti maschi o femmine, con età > 18 anni
9. Indice di massa corporea (BMI) del paziente > 18 kg/m² e peso > 40 kg
10. Uomini e donne potenzialmente fertili devono acconsentire all’uso di due metodi (uno per il paziente e uno per il partner) di forme di contraccezione medicalmente accettabili durante lo studio e per i 3 mesi successivi alla somministrazione dell’ultima dose del trattamento. Le pazienti in età fertile devono presentare un test di gravidanza negativo allo screening e al basale.
11. Pazienti in grado e desiderosi di attenersi alle procedure dello studio come da protocollo
12. Pazienti in grado di comprendere, firmare e datare il modulo di consenso informato fornito alla visita di screening che precede qualsiasi procedura protocollo-specifica
13. Pazienti in grado di comprendere la tessera del paziente e di seguire le procedure della tessera del paziente in caso di segni o sintomi di grave neutropenia o di tossicità cutanea grave, durante i primi 2 mesi di trattamento
14. Paziente coperto da assicurazione di rimborso per sunitinib

E.4

Principal exclusion criteria

1. Patient treated for a cancer other than GIST within 5 years before enrolment, with the exception of basal cell carcinoma or cervical cancer in situ
2. Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis
3. Patient presenting with cardiac disorders defined by at least one of the following conditions:
• Patient with recent cardiac history (within 6 months) of:
- Acute coronary syndrome
- Acute heart failure (class III or IV of the NYHA classification)
- Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)
• Patient with cardiac failure class III or IV of the NYHA classification
• Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block)
• Syncope without known aetiology within 3 months
• Uncontrolled severe hypertension, according ot the judgement of the investigator, or symptomatic hypertension
4. Patient with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent
5. Pregnant, or nursing female patient
For the QT/QTc study
1. Patients with a marked prolongation of QT/QTc interval (e.g. repeated demonstration of a QTc interval > 450 milliseconds)
2. Patient wih a history of additional risk factors for torsades de pointe (e.g. heart failure, hypokalemia, family history of Long QT Syndrome)
3. Patients using concomitant medications that prolong the QT/QTc interval (the list of medications is provided in the section “concomitant treatments”)
Previous treatment
1. Patient previously treated with a dose of imatinib > 800 mg
2. Previous treatment with sunitinib or kinase inhibitor other than imatinib
Wash-out
1. Treatment with any investigational agent within 4 weeks prior to baseline
2. Previous imatinib treatment should be definitely discontinued within 4 days prior randomisation and patient should have recovered from potential toxicity related to imatinib

1. Pazienti trattati per cancro diverso da GIST entro 5 anni dall’arruolamento, eccetto il carcinoma di cellule basali o cancro cervicale in situ
2. Pazienti con metastasi attive del sistema nervoso centrale (SNC) o con storia di metastasi del SNC
3. Pazienti che presentano una delle seguenti condizioni cardiache:
• Pazienti con recente (entro 6 mesi) storia clinica cardiaca di:
- Sindrome coronarica acuta
- Insufficienza cardiaca acuta (di classe III o IV secondo la classificazione NYHA)
- Aritmia ventricolare significativa (tachicardia ventricolare persistente, fibrillazione ventricolare, rianimazione dopo decesso)
• Pazienti con insufficienza cardiaca acuta di classe III o IV secondo la classificazione NYHA
• Pazienti con disordini severi di conduzione che non sono stati prevenuti con pacemaker permanente (blocco atrio-ventricolare di classe 2 o 3, blocco seno atriale)
• Sincope senza eziologia nota entro 3 mesi
• Ipertensione severa non controllata, secondo il giudizio dello sperimentatore, o ipertensione sintomatica
4. Pazienti con storia di scarsa compliance o storia di abuso di droga/alcool, o eccessivo consumo di bevande alcoliche che potrebbero interferire con la capacità di aderire al protocollo dello studio, o patologie psichiatriche attuali o pregresse che possono interferire con la capacità di aderire al protocollo dello studio o di rilasciare il consenso informato
5. Pazienti donne incinte o in allattamento
Per lo studio sul QT/QTc
1. Pazienti con un marcato prolungamento dell'intervallo QT/QTc (per esempio evidenza ripetuta di un intervallo QTc > 450 millisecondi)
2. Pazienti con anamnesi di fattori di rischio aggiuntivi per torsioni di punta (per esempio insufficienza cardiaca, ipokaliemia, anamnesi familiare di sindrome del QT lungo)
3. Pazienti che usano farmaci concomitanti i quali prolungano l'intervallo QT/QTc (l'elenco dei farmaci è fornito nella sezione "trattamenti concomitanti")
Trattamenti precedenti
1. Pazienti precedentemente trattati con imitinib ad un dosaggio > 800mg
2. Trattamenti precedenti con sunitinib o inibitori di chinasi diversi da imatinib
Wash-out
1. Trattamento con qualsiasi prodotto sperimentale entro 4 settimane prima del basale
2. Il trattamento precedente con imatinib deve essere definitivamente interrotto entro 4 giorni prima della randomizzazione e il paziente dovrebbe aver recuperato dalla tossicità potenziale correlata a imatinib

E.5 End points

E.5.1

Primary end point(s)

Overall Survival (OS)

Sopravvivenza totale (OS)

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 24

Settimana 24

E.5.2

Secondary end point(s)

• Efficacy
- Survival rate at weeks 8, 16, 24, and then every 12 weeks
- Overall Progression Free Survival (PFS) as evaluated by independent review and investigator
- PFS rate at weeks 8, 16, 24, and then every 12 weeks as evaluated by independent review and investigator
- Overall time to progression (TTP) as evaluated by independent review and investigator
- TTP rate at weeks 8, 16, 24, and then every 12 weeks as evaluated by independent review and investigator
- Overall Time to treatment failure (TTF)
- TTF rate at weeks 8, 16, 24, and then every 12 weeks
- Best Response rate as evaluated by independent review and investigator
- Objective Response rate: Complete Response (CR) or Partial response (PR) at weeks 8, 16, 24, and then every 12 weeks as evaluated by independent review and investigator
- Disease Control rate: CR + PR + stable disease (SD) at weeks 8, 16, 24, and then every 12 weeks as evaluated by independent review and investigator
• Safety
- Discontinuation for related adverse event (DAES)
- DAES rate at weeks 8, 16, 24, and then every 12 weeks
- Total Event Free Survival (TEFS)
- TEFS rate at weeks 8, 16, 24, and then every 12 weeks
- Safety Event Free Survival (SEFS)
- SEFS rate at weeks 8, 16, 24, and then every 12 weeks
- Related Grade 3 non haematological or any related grade 4 related adverse event
- Safety profile using the NCI CTCAE v4.03 classification
Quality of life
- Quality of Life according to the EORTC QLQ-C30 questionnaire at week 8, 16, 24 and then every 12 weeks
- ECOG Performance Status at week 8, 16, 24 and then every 12 weeks

• Efficacia
- Tasso di sopravvivenza alle settimane 8, 16 e 24, e poi ogni 12 settimane Sopravvivenza globale libera da progressione (PFS) secondo la valutazione di una revisione indipendente e dello sperimentatore
- Tasso di PFS alle settimane 8, 16 e 24, e poi ogni 12 settimane come valutato da una revisione indipendente e dallo sperimentatore
- Tempo totale fino alla progressione (TTP) come valutato da una revisione indipendente e dallo sperimentatore
- Tasso di TTP alle settimane 8, 16 e 24, e poi ogni 12 settimane come valutato da una revisione indipendente e dallo sperimentatore
- Tempo totale fino al fallimento della terapia (TTF)
- Tasso di TTF alle settimane 8, 16 e 24, e poi ogni 12 settimane
- Miglior tasso di risposta secondo la valutazione di una revisione indipendente e dello sperimentatore
- Tasso di risposta obiettiva: risposta completa (CR) o risposta parziale (PR) alle settimane 8, 16 e 24, e poi ogni 12 settimane come valutato da una revisione indipendente e dello sperimentatore
- Tasso di Controllo della malattia: CR + PR + malattia stabile (SD) alle settimane 8, 16, 24, e poi ogni 12 settimane come valutati da una revisione indipendente e dallo sperimentatore
• Sicurezza
- Sospensione della terapia per eventi avversi correlati (DAES)
- Tasso di DAES alle settimane 8, 16, 24, e poi ogni 12 settimane
- Sopravvivenza totale libera da eventi (TEFS)
- Tasso di TEFS alle settimane 8, 16, 24, e poi ogni 12 settimane
- Sicurezza di sopravvivenza libera da eventi (SEFS)
- Tasso di SEFS alle settimane 8, 16, 24, e poi ogni 12 settimane
- Eventi avversi correlati di Grado 3 non ematologici o qualsiasi evento correlato di grado 4
- Profilo di sicurezza utilizzando la classificazione NCI CTCAE v4.03
• Qualità di vita
- Qualità di vita secondo l'EORTC QLQ-C30 alla settimana 8, 16, 24 e poi ogni 12 settimane
- ECOG Performance Status alla settimana 8, 16, 24 e poi ogni 12 settimane

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 24

Settimana 24

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

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

QT/QTc study

Studio QT/QTc

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

Yes

E.8.2.3.1

Comparator description

SUTENT

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

United States

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

Patient could be treated until disease progression, toxicity without clinical benefit, or consent withdrawal.

Paziente potrebbe essere trattato fino a progressione della malattia, tossicità limitante senza beneficio clinico o ritiro del consenso

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero