Clinical Trials Register

Summary
EudraCT Number:	2012-002940-26
Sponsor's Protocol Code Number:	212082PCR3011
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:	2012-11-06
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2012-002940-26

A.3

Full title of the trial

A Randomized, Double-blind, Comparative Study of ZYTIGA (Abiraterone Acetate) Plus Low-dose Prednisone Plus Androgen Deprivation Therapy (ADT) Versus ADT Alone in Newly Diagnosed Subjects With High-Risk, Metastatic Hormone-Naive Prostate Cancer (mHNPC)

Studio comparativo, randomizzato, in doppio cieco su ZYTIGA (abiraterone acetato) piu' prednisone a basso dosaggio piu' terapia androgeno-soppressiva (ADT) rispetto a sola ADT, in soggetti con diagnosi recente di carcinoma prostatico metastatico naive al trattamento ormonale (mHNPC), ad alto rischio

A.3.1

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

A Study of ZYTIGA and Prednisone with Androgen Deprivation Therapy (ADT) compared to ADT Alone in men newly Diagnosed (within the previous 3 months) with High-Risk, Metastatic Prostate Cancer

Studio su ZYTIGA più prednisone più terapia androgeno-soppressiva (ADT) rispetto a sola ADT, in soggetti con diagnosi recente di carcinoma prostatico metastatico naïve al trattamento ormonale (mHNPC), ad alto rischio

A.4.1

Sponsor's protocol code number

212082PCR3011

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 N.V.
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 CILAG SPA
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	JANSSEN CILAG INTERNATIONAL
B.5.2	Functional name of contact point	CLINICAL REGISTRY GROUP
B.5.3	Address:
B.5.3.1	Street Address	Archimedesweg 29
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333CM
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31 071 5242166
B.5.5	Fax number	+31 071 5242110
B.5.6	E-mail	ClinicalTrialsEU@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	ZYTIGA
D.2.1.1.2	Name of the Marketing Authorisation holder	JANSSEN-CILAG INTERNATIONAL NV
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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	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.3.9.2	Current sponsor code	JNJ-212082
D.3.9.4	EV Substance Code	SUB31647
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	250
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	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	PREDNISONE
D.2.1.1.2	Name of the Marketing Authorisation holder	ACIS ARZNEIMITTEL GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	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	PREDNISONE
D.3.9.1	CAS number	53-03-2
D.3.9.4	EV Substance Code	SUB10020MIG
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	5
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	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

Metastatic Hormone-Naive Prostate Cancer (mHNPC)

Carcinoma metastatico della prostata di nuova diagnosi non sottoposto a precedente terapia ormonale

E.1.1.1

Medical condition in easily understood language

Prostate Cancer

Tumore alla prostata

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	LLT
E.1.2	Classification code	10029002
E.1.2	Term	Neoplasm of the prostate
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 determine whether ZYTIGA in combination with low-dose prednisone and ADT is superior to ADT alone in improving survival in subjects with mHNPC with high risk prognostic factors.

L’obiettivo principale consiste nel determinare se ZYTIGA in combinazione con prednisone a basso dosaggio e ADT (Androgen Deprivation Therapy, ADT) sia superiore alla sola ADT nel migliorare le aspettative di vita in soggetti affetti da mHNPC ormonale (Metastatic Hormone-Naïve Prostate Cancer, mHNPC) con fattori prognostici ad alto rischio.

E.2.2

Secondary objectives of the trial

To evaluate the clinically relevant improvements as well as the safety of ZYTIGA plus low-dose prednisone and ADT compared to ADT alone. •To identify microRNA (miRNA) and mRNA profiles predictive of ZYTIGA response or resistance.

Gli obiettivi secondari consistono nel valutare i miglioramenti rilevanti dal punto di vista clinico, oltre alla sicurezza di ZYTIGA più prednisone a basso dosaggio e ADT rispetto alla sola ADT e nell’identificare i profili di microRNA (miRNA) e mRNA predittivi della risposta o resistenza di ZYTIGA in questa popolazione di pazienti.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Newly diagnosed metastatic prostate cancer within 3 months prior to randomization with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology 2. Distant metastatic disease documented by positive bone scan or metastatic lesions on computed tomography or magnetic resonance imaging scan 3. Two of the following high-risk prognostic factors: Gleason score of >=8; presence of 3 or more lesions on bone scan; presence of measurable visceral (excluding lymph node disease) metastasis 4. Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2 5. Adequate hematologic, hepatic, and renal function 6. Agrees to protocol-defined use of effective contraception

1.Diagnosi recente di carcinoma prostatico metastatico entro 3 mesi prima della randomizzazione con adenocarcinoma prostatico confermato mediante esame istologico o citologico, senza differenziazione neuroendocrina o istologia a piccole cellule. 2.Malattia metastatica distante documentata da scintigrafia ossea positiva o lesioni metastatiche evidenziate da TC o RMI. 3.Due dei seguenti fattori prognostici ad alto rischio: -punteggio di Gleason ≥ 8;  -presenza di 3 o più lesioni alla scintigrafia ossea; -presenza di metastasi viscerali misurabili (escluse patologie dei linfonodi) (RECIST 1.1). 4.Stato prestazionale secondo l’Eastern Cooperative Oncology Group (ECOG) di grado 0, 1 o 2 5.Adeguata funzionalità ematologica, epatica e renale 6.Accettazione di contraccezione efficace come da Protocollo

E.4

Principal exclusion criteria

1. Active infection or other medical condition that would make prednisone use contraindicated 2. Any chronic medical condition requiring a higher systemic dose of corticosteroid than 5 mg prednisone per day 3. Pathological finding consistent with small cell carcinoma of the prostate 3. Known brain metastasis 4. Any prior pharmacotherapy, radiation therapy, or surgery with curative intent for metastatic prostate cancer (the following exception is allowed: up to 3 months of androgen deprivation therapy (ADT) with lutenizing hormone releasing hormone agonists or orchiectomy with or without concurrent anti-androgens prior to patients randomization is permitted; patients may have one course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered prior to randomization) 5. Radiation or surgical therapy could not have been initiated 4 weeks after the start of ADT or orchiectomy 6. Uncontrolled hypertension (systolic blood pressure >=160 mmHg or diastolic BP >=95 mmHg; patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment) 7. Active or symptomatic viral hepatitis or chronic liver disease 8. History of adrenal dysfunction 9. Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of <50% at baseline 10. Atrial fibrillation, or other cardiac arrhythmia requiring pharmacotherapy 11. Other malignancy (within 5 years), except non-melanoma skin cancer 12. Administration of an investigational therapeutic or invasive surgical procedure (not including surgical castration) within 30 days of Cycle 1 Day 1 or currently enrolled in an investigational study 13. Any condition or situation which, in the opinion of the investigator, would put the patient at risk, may confound study results, or interfere with the patient's participation in this study

1. Infezione attiva o altra patologia medica che renderebbe controindicato l’impiego di prednisone. 2. Qualsiasi patologia medica cronica che necessita di una dose sistemica maggiore di corticosteroide rispetto ai 5 mg/die di prednisone. 3. Risultato patologico che evidenzi un carcinoma prostatico a piccole cellule. 4. Metastasi cerebrale nota. 5. Qualsiasi terapia farmacologica, radioterapia o intervento chirurgico precedente con intento curativo di carcinoma prostatico metastatico. Sono consentite le seguenti eccezioni:  sono consentiti fino a 3 mesi di ADT con agonisti LHRH o orchiectomia con o senza antiandrogeni concomitanti prima della randomizzazione dei soggetti;  I soggetti possono avere effettuato radioterapia con intento palliativo o terapia chirurgica per trattare i sintomi della patologia metastatica (per esempio rischio di compressione vertebrale o sintomi ostruttivi) se somministrate prima della randomizzazione. Non sono ammesse radioterapia o chirurgia 4 settimane dopo l’inizio dell’ADT o dopo l’orchiectomia. 6. Ipertensione non controllata (pressione sistolica ≥ 160 mmHg o diastolica ≥ 95 mmHg). Sono ammessi i soggetti con anamnesi di ipertensione, purché la pressione sanguigna sia controllata da un trattamento anti-ipertensivo. 7. Epatite virale attiva o sintomatica o patologia epatica cronica. 8. Anamnesi di disfunzione surrenale. 9. Cardiopatia clinicamente significativa con evidenza di infarto miocardico, o eventi trombotici arteriosi manifestatisi negli ultimi 6 mesi, angina grave o instabile, o cardiopatia di classe II-IV della New York Heart Association (NYHA) o misurazione della frazione di eiezione basale < 50%. 10. Fibrillazione atriale o altra aritmia cardiaca che necessiti di farmacoterapia. 11. Altra patologia maligna (nell’arco di 5 anni), eccetto il tumore cutaneo non melanoma. 12. Somministrazione di una procedura terapeutica o chirurgica invasiva sperimentale (esclusa la castrazione chirurgica) entro 30 giorni dal Ciclo 1 Giorno 1 o attualmente arruolati in uno studio sperimentale. 13. Qualsiasi patologia o situazione che, a giudizio dello sperimentatore, metterebbe il soggetto a rischio, potrebbe confondere i risultati dello studio o interferire con la partecipazione del soggetto al presente studio.

E.5 End points

E.5.1

Primary end point(s)

Overall survival

Sopravvivenza

E.5.1.1

Timepoint(s) of evaluation of this end point

Randomization up to the time of death from any cause

Dalla randomizzazione al decesso per qualsiasi causa

E.5.2

Secondary end point(s)

1) Radiographic progression-free survival 2) Time to next subsequent therapy for prostate cancer 3) Time to initiation of chemotherapy 4) Time to prostate specific antigen progression 5) Time to next skeletal-related event

1) Sopravvivenza senza progressione di malattia al riscontro radiografico 2) Tempo fino alla successiva terapia per carcinoma prostatico 3) Tempo fino all’inizio di chemioterapia 4) Tempo fino alla progressione dell’antigene prostatico specifico 5) Tempo al successivo eventi che interessa lo scheletro

E.5.2.1

Timepoint(s) of evaluation of this end point

1From randomization, up to disease progression or death from any cause (up to Month 60) 2, 3 & 4) From randomization to time to the occurrence of each event 5) From randomization to time to the occurrence of one of the following: clinical fracture, spinal cord compression, palliative radiation to bone, surgery to bone

1 Dalla randomizzazione fino a progressione di malattia o morte per qualsiasi causa (fino al mese 60) 2,3 e 4 Dalla randomizzazione fino all’accadere di qualsiasi evento 5 Dalla randomizzazione fino all’accadere di uno dei seguenti: frattura, compressione spinale, radiazione palliativa alle ossa, chirurgia alle ossa

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

Biomarkers

Biomarcatori

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

Yes

E.8.2.3.1

Comparator description

antagonisti LHRH o orchiectomia

LHRH antagonists or ochiectomy

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

123

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

Argentina

Australia

Brazil

Canada

Chile

China

Colombia

Israel

Japan

Korea, Democratic People's Republic of

Malaysia

Mexico

New Zealand

Peru

Russian Federation

Singapore

South Africa

Turkey

Ukraine

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

Number of subjects for this age range:

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:

F.2 Gender

F.2.1

Female

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

667

F.4.2.2

In the whole clinical trial

1270

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)

In the event of a positive study result at either of the interim analyses or at the final analysis, all subjects will have the opportunity to enroll in an open-label Extension Phase of this protocol. The Extension Phase will allow subjects to receive active drug (ZYTIGA plus prednisone) until ZYTIGA becomes commercially available in the subject's country

Nel caso di esito positivo dello studio alla interim o all'analisi finale, tutti i soggetti avranno l'opportunità di partecipare alla fase di estensione di questo protocollo. La fase di estensione permetterà ai soggetti di ricevere il farmaco attivo (ZYTIGA + PREDNISONE) fino a quando ZYTIGA sarà disponibile in commercio nel paese interessato

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

2012-12-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-10-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-02-13

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials