Clinical Trials Register

Summary
EudraCT Number:	2015-001630-21
Sponsor's Protocol Code Number:	BAY59-7939/39039039STM4001/18262
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:	2021-06-08
Trial results	View 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

2015-001630-21

A.3

Full title of the trial

Full title of the trial (up to 2000 characters) (Titolo completo della sperimentazione, in inglese): Efficacy and Safety of
Rivaroxaban Prophylaxis Compared with Placebo in Ambulatory Cancer Patients Initiating Systemic Cancer Therapy and at High Risk
for Venous Thromboembolism

Efficacia e sicurezza della profilassi con rivaroxaban rispetto al placebo nei pazienti
oncologici in regime ambulatoriale che avviano la terapia antitumorale sistemica e ad alto rischio di tromboembolia venosa

A.3.1

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

A Study to Evaluate the Efficacy and Safety of Rivaroxaban Venous
Thromboembolism (VTE) Prophylaxis in Ambulatory Cancer Participants

Uno studio per valutare l'efficacia e
sicurezza della profilassi con rivaroxaban per tromboembolia venosa in pazienti oncologici in regime ambulatoriale

A.3.2

Name or abbreviated title of the trial where available

A Study to Evaluate the Efficacy and Safety of Rivaroxaban Venous Thromboembolism (VTE) Prophylaxis

Uno studio per valutare l'efficacia e sicurezza della profilassi con rivaroxaban per tromboembolia v

A.4.1

Sponsor's protocol code number

BAY59-7939/39039039STM4001/18262

A.5.4

Other Identifiers

Name:

Number:

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	JANSSEN CILAG INTERNATIONAL NV
B.1.3.4	Country	Belgium
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	Janssen Research & Development, LLC - Stati Uniti
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Janssen Research and Development
B.5.2	Functional name of contact point	Daniel Yannicelli
B.5.3	Address:
B.5.3.1	Street Address	1000 Route 202
B.5.3.2	Town/ city	Raritan, NJ
B.5.3.3	Post code	00869
B.5.3.4	Country	United States
B.5.4	Telephone number	0019089275625
B.5.5	Fax number	0019089275625
B.5.6	E-mail	HYannice@its.jnj.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	Yes
D.2.1.1.1	Trade name	XARELTO¿ 10 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Pharma AG
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	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	RIVAROXABAN
D.3.9.1	CAS number	366789-02-8
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	BAY 59-7939
D.3.9.4	EV Substance Code	SUB29263
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	10
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	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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Venous thromboembolism (VTE)

tromboembolia venosa (TEV)

E.1.1.1

Medical condition in easily understood language

Blood clot in a vein

Coagulo di sangue in una vena

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10066899
E.1.2	Term	Venous thromboembolism
E.1.2	System Organ Class	100000004866

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary efficacy objective is to demonstrate
that rivaroxaban is superior to placebo for reducing the risk of the primary composite outcome as defined by objectively confirmed symptomatic lower extremity proximal DVT, asymptomatic lower extremity Proximal DVT, symptomatic upper extremity DVT, symptomatic non-fatal PE, incidental PE, and VTE-related death in ambulatory adult subjects with various cancer types receiving systemic cancer therapy who are at high risk of developing a VTE.

L¿obiettivo di efficacia primario consiste nel dimostrare che rivaroxaban ¿ superiore al placebo nel
ridurre il rischio di esito composito primario come definito da TVP prossimale sintomatica alle estremit¿ inferiori confermata in
modo obiettivo, TVP prossimale asintomatica alle estremit¿ inferiori, TVP sintomatica alle estremit¿ superiori, EP sintomatica non
fatale, EP incidentale e decesso correlato alla TEV in soggetti adulti in regime ambulatoriale con vari tipi di tumore, sottoposti a
terapia antitumorale sistemica ad alto rischio di sviluppare una TEV.

E.2.2

Secondary objectives of the trial

The key secondary efficacy objectives of this study are to compare the efficacy of rivaroxaban with placebo for reducing risk of symptomaticVTE events and VTE--related deaths, and all-cause mortality in
ambulatory adult subjects with various cancer types receiving systemic cancer therapy who are at high risk of developing a VTE. Other secondary efficacy objectives include the evaluation of the individual
components of the primary efficacy composite variable, confirmed fatal/non-fatal arterial thromboembolism (ATE) events, confirmed
fatal/non-fatal visceral VTE events, symptomatic lower extremity distal DVT, a composite of symptomatic lower extremity proximal DVT,
asymptomatic lower extremity proximal DVT, symptomatic upper extremity DVT, symptomatic non-fatal PE, incidental PE, and all-cause mortality, and a composite of symptomatic lower extremity proximal
DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, symptomatic non-fatal PE, and VTE-related deaths.

I principali obiettivi di efficacia secon consistono nel confrontare l¿efficacia di rivaroxaban rispetto a quella di placebo per la riduzione del rischio di eventi di TEV sintomatica, decessi correlati alla TEV e mortalit¿ per qualsiasi causa in soggetti adulti in regime ambulatoriale con vari tipi di tumore, sottoposti a terapia antitumorale sistemica ad alto rischio di sviluppare una TEV. Altri obiettivi di efficacia second includono la valutazione dei componenti individuali della variabile composita di efficacia primaria, TEA fatali/non fatali confermati, eventi di TEV viscerale fatali/non fatali confermati, TVP distale sintomatica alle estremit¿ inferiori, un composito di TVP prossimale sintomatica alle estremit¿ inferiori, TVP prossimale asintomatica alle estremit¿ inferiori, TVP sintomatica alle estremit¿ superiori, EP sintomatica non fatale, EP incidentale, mortalit¿ per qualsiasi causa e un composito di TVP pross sintoma alle estremit¿ infer, TVP distale sintomaticestrem infer

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Histologically confirmed solid malignancy including but not limited to: pancreas, lung, stomach, colon, rectum, bladder, breast,
ovary, renal or lymphoma (hematologic), with locally advanced or metastatic disease
- Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 02
- Have a Khorana thromboembolic risk Score greater than or equal to (>=) 2
- Creatinine clearance (CrCl) >= 30 milliliter per minute (mL/min)
- Plan to initiate systemic cancer therapy within ±1 week of receiving the first dose of study drug with the intention of receiving systemic cancer therapy during the double-blind treatment period for an intended duration determined by the treating oncologist according to standard protocols of clinical care.

- Essere affetto da tumore maligno solido confermato istologicamente inclusi, in via non limitativa: pancreas, polmone, stomaco,
colon, retto, vescica, seno, ovaie, reni o linfoma (ematologico), con malattia localmente avanzata o metastatica.
- Avere uno stato prestazionale pari a 0-2 secondo il Gruppo cooperativo orientale di oncologia (ECOG)
- Presentare un rischio tromboembolico con punteggio di Khorana =2
- Avere un’adeguata funzione renale: CrCl =30 mL/min
- Programmare l’avvio di una terapia antitumorale sistemica ±1 settimana dalla prima dose del farmaco dello studio con l’intenzione di ricevere la terapia antitumorale sistemica durante il periodo di trattamento in doppio cieco per una durata prevista determinata dall’oncologo curante in base ai protocolli standard di cure cliniche.

E.4

Principal exclusion criteria

- Diagnosis of primary brain tumors
- Known history of brain metastases
- Bleeding diathesis, hemorrhagic lesions, active bleeding, and other conditions with a high risk for bleeding
- Hematologic malignancies with the exception of lymphoma
- Platelet count less than (<) 50,000/millimeter^3 (mm^3), Life expectancy of less than or equal to (<=) 6 months

- Presenta una diagnosi di tumori cerebrali primari
- Presenta un’anamnesi nota di metastasi cerebrali
- Presenta diatesi emorragica, lesioni emorragiche, emorragia attiva e altre patologie con alto rischio di emorragia
- È affetto/a da tumori maligni ematologici a eccezione del linfoma
- conta piastrinica <50.000/mm3, aspettativa di vita inferiore o uguale (<=) 6 mesi

E.5 End points

E.5.1

Primary end point(s)

1)Primary Efficacy Composite Endpoint is
Time From Randomization to First Occurrence of Objectively Confirmed Symptomatic and Asymptomatic Lower Extremity Proximal
DVT,Symptomatic Upper Extremity DVT, Symptomatic Non-Fatal PE, Incidental PE, VTE-Related Death 2) The Primary Safety
Objective of This Study is to Assess the Major Bleeding Events as Defined by ISTH

1) L’endpoint composito di efficacia primario è il periodo di tempo dalla randomizzazione alla prima
occorrenza di TVP prossimale sintomatica e asintomatica alle estremità inferiori confermata in modo obiettivo, TVP sintomatica alle
estremità superiori, EP sintomatica non fatale, EP incidentale o decesso correlato alla TEV 2) L’obiettivo primario di sicurezza di
questo studio è valutare gli eventi di emorragia maggiore secondo la definizione dell’ISTH

E.5.1.1

Timepoint(s) of evaluation of this end point

1)From Randomization to Day 180 (+3 Days) as Adjudicated by an Independent CEC 2) From the Time of Randomization
to Two Days After the Last Dose of Study Drug

1) Dalla randomizzazione al giorno 180 (+3 Giorni) come giudicato da un
CEC indipendente 2) Dal momento della randomizzazione a due giorni dopo l'ultima dose del farmaco in studio

E.5.2

Secondary end point(s)

1)Efficacy endpoint: Symptomatic VTE
Events and VTE Related Deaths 2) Efficacy endpoint: All-cause Mortality 3) Safety Endpoints Include the Proportion of Clinically
Relevant Non-Major Bleeding, Minor Bleeding, any Bleeding (Defined as Major, Clinically Relevant Non-Major, and Minor Bleeding)
4) Safety endpoint: All-cause Mortality 5) Number of Participants with Adverse Events (AEs) and Serious AEs

1) Endpoint di efficacia: eventi TEV sintomatici e decessi correlati a TVE
2) Endpoint di efficacia: mortalit¿ per tutte le cause
3) Gli endpoint di sicurezza includono percentuali di emorragie non maggiori clinicamente rilevanti, emorragie minori e qualsiasi
emorragia (definita maggiore, non maggiore clinicamente rilevante e minore, secondo la definizione dell¿ISTH)
4) Endpoint di sicurezza: mortalit¿ per tutte le cause
5) Numero di partecipanti con eventi avversi (EA) e EA gravi

E.5.2.1

Timepoint(s) of evaluation of this end point

1) and 2): Up to Day 180+3 3) From the Time of Randomization to Two Days After the Last Dose of Study Drug 4) Up to Day 180
5) Screening up to follow-up (30 days after last dose administration)

1) e 2): Fino al giorno 180 + 3 3) Dal momento della randomizzazione a due
giorni dopo l'ultima dose del farmaco in studio 4) Fino a giorno 180 5) Screening fino al follow-up (30 giorni dopo la somministrazione dell'ultima dose)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

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

E.6.12

Pharmacoeconomic

E.6.13

Others

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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)

E.8.2.2

Placebo

Yes

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

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

Information not present in EudraCT

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

Canada

United States

Belgium

Germany

United Kingdom

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

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:

560

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

140

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

250

F.4.2.2

In the whole clinical trial

700

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)

none

nessuno

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

2016-06-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-05-12

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

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