Clinical Trials Register

Summary
EudraCT Number:	2013-000722-54
Sponsor's Protocol Code Number:	MDV3100-10
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:	2013-10-21
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

2013-000722-54

A.3

Full title of the trial

A Phase 4, Randomized, Double Blind, Placebo Controlled Study of Continued Enzalutamide Treatment Beyond Progression in Patients With Chemotherapy Naïve Metastatic Castration Resistant Prostate Cancer.

Studio di fase 4, randomizzato, in doppio cieco, controllato con placebo teso a valutare il trattamento continuato con enzalutamide in seguito alla progressione in pazienti affetti da cancro alla prostata metastatico resistente alla castrazione e non trattati in precedenza con chemioterapia

A.3.1

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

An International Study to Evaluate the effectiveness of continuing treatment of enzalutamide after PSA Progression in Patients who have not yet received chemotherapy.

Studio internazionale per valutare l’efficacia del trattamento continuo con Enzalutamide dopo la progressione della PSA in pazienti che non hanno ancora ricevuto la chemioterapia.

A.4.1

Sponsor's protocol code number

MDV3100-10

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	Medivation, Inc.
B.1.3.4	Country	United States
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	Medivation, Inc.
B.4.2	Country	United States
B.4.1	Name of organisation providing support	Astellas Pharma Global Development, Inc.
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	Medivation, Inc.
B.5.2	Functional name of contact point	Medical Officer
B.5.3	Address:
B.5.3.1	Street Address	525 Market Street, 36th Floor
B.5.3.2	Town/ city	San Francisco, CA
B.5.3.3	Post code	94105
B.5.3.4	Country	United States
B.5.4	Telephone number	14155433470
B.5.5	Fax number	14155433411

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	Xtandi
D.2.1.1.2	Name of the Marketing Authorisation holder	Astellas Pharma Europe B.V.
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.3.1	Product name	Xtandi (enzalutamide)
D.3.2	Product code	MDV3100
D.3.4	Pharmaceutical form	Capsule, soft
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	ENZALUTAMIDE
D.3.9.1	CAS number	915087-33-1
D.3.9.2	Current sponsor code	MDV3100
D.3.9.3	Other descriptive name	Xtandi
D.3.9.4	EV Substance Code	SUB77412
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	40
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	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	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.3.1	Product name	ZYTIGA (abiraterone acetate)
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	Abiraterone acetate
D.3.9.1	CAS number	154229-18-2
D.3.9.3	Other descriptive name	ABIRATERONE ACETATE
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: 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.2.1.2	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.3.4	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.3.9.3	Other descriptive name	PREDNISONE
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Prednisolone
D.3.9.3	Other descriptive name	PREDNISOLONE
D.3.9.4	EV Substance Code	SUB10018MIG
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	Capsule, soft
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

Patients With Chemotherapy Naïve Metastatic Castration Resistant Prostate Cancer.

Pazienti affetti da cancro alla prostata metastatico, resistente alla castrazione e che non abbiano mai ricevuto chemioterapia.

E.1.1.1

Medical condition in easily understood language

Prostate cancer.

Cancro 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	PT
E.1.2	Classification code	10060862
E.1.2	Term	Prostate cancer
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 determine the efficacy of combination treatment with continued enzalutamide plus abiraterone acetate (abiraterone) and prednisone (or prednisolone) compared with placebo plus abiraterone and prednisone as measured by progression free survival (PFS).

Determinare l'efficacia del trattamento di associazione a base di enzalutamide continuativa con abiraterone acetato (abiraterone) e prednisone (o prednisolone) rispetto a placebo con abiraterone e prednisone misurandola in termini di sopravvivenza libera da progressione (PFS).

E.2.2

Secondary objectives of the trial

To evaluate the effect of combination treatment with continued enzalutamide plus abiraterone and prednisone compared with placebo plus abiraterone and prednisone after PSA progression on treatment with enzalutamide in patients with chemotherapy naïve metastatic CRPC on the following: Time to PSA progression, PSA response, objective response rate, rate of pain progression, time to first use of subsequent antineoplastic therapy for prostate cancer, quality of life and safety.

Valutare l'effetto del trattamento di associazione a base di enzalutamide continuativa con abiraterone e prednisone rispetto a placebo con abiraterone e prednisone dopo progressione del PSA durante il trattamento con enzalutamide in pazienti non trattati in precedenza con chemioterapia affetti da CRPC metastatico in termini di: Tempo alla progressione del PSA, Risposta del PSA, Tasso di risposta obiettiva, Tasso di progressione del dolore, Tempo al primo utilizzo di terapia antitumorale successiva per il cancro della prostata, Qualità della vita, Sicurezza.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Age 18 years or older and willing and able to provide informed consent;
Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, or signet cell or small cell features;
Presence of metastatic disease as assessed by CT/MRI and/or whole body radionuclide bone scan;
Throughout study, ongoing androgen deprivation therapy with a GnRH agonist/antagonist or prior bilateral orchiectomy (medical or surgical castration);
Testosterone ≤ 1.73 nmol/L (≤ 50 ng/dL) at screening;
Progressive disease on androgen deprivation therapy at screening defined as a minimum of 3 sequential rising PSA values (PSA1 < PSA2 < PSA3) assessed by the local laboratory (local PSA) with an interval of ≥ 1 week between each determination;
The most recent local PSA and the initial screening PSA assessed by the central laboratory should be ≥ 2 µg/L (≥ 2 ng/mL). In the event of prior androgen receptor inhibitor use, the most recent local PSA and the initial screening PSA assessed by the central laboratory (central PSA) must be obtained at least 4 weeks after the last dose of the androgen receptor inhibitor.

Età uguale o superiore ai 18 anni, intenzionato e in grado di fornire il consenso informato.
Affetto da adenocarcinoma della prostata istologicamente o citologicamente confermato, senza differenziazione neuroendocrina, a cellule ad anello o a piccole cellule.
Presenza di malattia metastatica valutata mediante TAC/RM e/o scintigrafia ossea total body con radionuclide.
Per l'intera durata dello studio, terapia di deprivazione androgenica a base di agonista/antagonista del GnRH in corso o orchiectomia bilaterale precedente (castrazione medica o chirurgica).
Testosterone ≤ 1,73 nmol/l (≤ 50 ng/dl) allo screening.
Malattia in progressione durante la terapia di deprivazione androgenica allo screening, definita da almeno 3 valori sequenziali di PSA in aumento (PSA1 < PSA2 < PSA3) determinati dal laboratorio locale (PSA locale) con un intervallo ≥ 1 settimana tra ciascuna misurazione.
Il PSA locale più recente e il PSA iniziale allo screening valutato dal laboratorio centrale (PSA centrale) devono essere ≥ 2 µg/l (≥ 2 ng/ml). In caso di utilizzo precedente di inibitori del recettore degli androgeni, il PSA locale più recente e il PSA iniziale allo screening valutati dal laboratorio centrale (PSA centrale) devono essere stati determinati almeno 4 settimane dopo l'ultima dose dell'inibitore del recettore degli androgeni.

E.4

Principal exclusion criteria

Prior cytotoxic chemotherapy, aminoglutethimide, ketoconazole, abiraterone acetate, or enzalutamide for the treatment of prostate cancer or participation in a clinical trial of an investigational agent that inhibits the androgen receptor or androgen synthesis (unless treatment was placebo);
Medical contraindication to prednisone use; Treatment with hormonal therapy (eg, androgen receptor inhibitors, 5 alpha reductase inhibitors) or biologic therapy for prostate cancer (other than denosumab, GnRH agonist/antagonist therapy, or corticosteroid therapy) within 4 weeks of screening;
Use of an investigational agent within 4 weeks of the screening visit;
Current or previously treated brain metastasis or active leptomeningeal disease.

Trattamento precedente con chemioterapia citotossica, amminoglutetimide, ketoconazolo, abiraterone acetato o enzalutamide per il trattamento del cancro della prostata oppure partecipazione a una sperimentazione clinica con un farmaco sperimentale che inibisce il recettore degli androgeni o la sintesi degli androgeni (a meno che il trattamento sia con placebo).
Controindicazione medica all'uso di prednisone.
Trattamento con terapia ormonale (ad es., inibitori del recettore degli androgeni, inibitori della 5-alfa reduttasi) o terapia biologica per il cancro della prostata (ad eccezione di denosumab, terapia a base di agonisti/antagonisti del GnRH o terapia con corticosteroidi) nelle 4 settimane precedenti allo screening.
Trattamento con un farmaco sperimentale nelle 4 settimane precedenti alla visita di screening.
Metastasi cerebrale in atto o trattata in precedenza oppure malattia leptomeningea in atto.

E.5 End points

E.5.1

Primary end point(s)

Progression Free Survival

sopravvivenza libera da progressione (PFS)

E.5.1.1

Timepoint(s) of evaluation of this end point

PFS is defined as the time from randomization to the earliest objective evidence of radiographic progression, unequivocal clinical progression, or death on study (death within 112 days of treatment discontinuation without objective evidence of radiographic progression), whichever occurs first.

La PFS è definita come il lasso di tempo che intercorre tra la randomizzazione e la prima evidenza obiettiva di progressione radiografica, inequivocabile progressione clinica o decesso durante lo studio (decesso entro 112 giorni dall'interruzione del trattamento senza evidenza obiettiva di progressione radiografica), a seconda di quale evento si verifichi per primo.

E.5.2

Secondary end point(s)

Time to PSA progression

Tempo alla progressione della PSA

E.5.2.1

Timepoint(s) of evaluation of this end point

Time to PSA progression is defined as the time from randomization to the date of the first PSA value demonstrating progression, which must be subsequently confirmed.

Per tempo alla progressione del PSA si intende il lasso di tempo che intercorre tra la randomizzazione e la data del primo valore di PSA confermato che dimostra progressione, che deve essere successivamente confermato.

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

Quality of life.

Qualità della vita

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

Yes

E.8.1.7.1

Other trial design description

Periodo 1: trattamento in aperto con Enzalutamide

Period 1: enzalutamide open-label treatment

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

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

Australia

Belgium

Denmark

Finland

France

Germany

Italy

Spain

Sweden

Russian Federation

Slovakia

United Kingdom

United States

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

Study drugs will continue until disease progression (as defined by radiographic imaging or unequivocal clinical progression), intolerable toxicity, patient withdrawal, or death on study, whichever occurs first.

La somministrazione dello studio continuerà fino alla progressione della malattia (come definita dalla progressione radiografica e dalla progressione clinica inequivocabile), tossicità intollerabile, ritiro del paziente, o morte nel corso dello studio, qualunque avvenga per prima.

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

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:

175

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

325

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

324

F.4.2.2

In the whole clinical trial

500

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)

Standard of care for patients with progressive metastatic prostate cancer

Trattamento standard per i pazienti con cancro alla prostata metastatico progressivo.

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

2014-01-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-05-06

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

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