Clinical Trials Register

Summary
EudraCT Number:	2015-004596-72
Sponsor's Protocol Code Number:	EXCALIBUR
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:	2021-02-09
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

2015-004596-72

A.3

Full title of the trial

A phase II study evaluating the efficacy of enzalutamide and the role of ARv7 in metastatic castration resistant prostate cancer (mCRPC) patients with visceral disease

Studio di fase II per valutare l’efficacia di Enzalutamide e il ruolo di ARv7 in pazienti affetti da carcinoma della prostata metastatico resistente alla castrazione con malattia viscerale

A.3.1

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

Study evaluating efficacy of enzalutamide and variants of androgens receptor in metastatic castration resistant prostate cancer patients
with visceral disease

Studio sull'efficacia di enzalutamide e sulle varianti del recettore per gli androgeni in pazienti affetti da carcinoma della prostata metastatico resistente alla castrazione con malattia viscerale

A.3.2

Name or abbreviated title of the trial where available

EXCALIBUR

A.4.1

Sponsor's protocol code number

EXCALIBUR

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN00000000

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00000000

A.5.3

WHO Universal Trial Reference Number (UTRN)

U0000-0000-0000

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	Astellas Pharma Europe
B.4.2	Country	Italy
B.4.1	Name of organisation providing support	Fondazione IRCCS Istituto Nazionale Tumori
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 IRCCS Istituto Nazionale Tumori
B.5.2	Functional name of contact point	clinical trial center
B.5.3	Address:
B.5.3.1	Street Address	via giacomo 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	0223903817
B.5.5	Fax number	0223903991
B.5.6	E-mail	trialcenter@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	XTANDI - "40 MG - CAPSULA MOLLE - USO ORALE - BLISTER (PVC/PCTFE/ALU)" 112 CAPSULE
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	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	Xtandi
D.3.2	Product code	[Xtandi]
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	NA
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	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

metastatic prostate cancer resistant to castration with visceral disease

carcinoma della prostata metastatico resistente alla castrazione con malattia viscerale

E.1.1.1

Medical condition in easily understood language

Metastatic castration resistant prostate cancer previously treated with hormonal treatment/chemotherapy with at least one visceral site of disease (lung, liver, lymphnodes)

carcinoma della prostata che ha già ricevuto un trattamento ormonale/chemioterapico con malattia metastatica in almeno una sede viscerale (polmone , fegato , linfonodi)

E.1.1.2

Therapeutic area

Diseases [C] - Male diseases of the urinary and reproductive systems [C12]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10007453
E.1.2	Term	Carcinoma of the prostate metastatic
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

Clinical benefit, in terms of disease control at 3 months (DCR) of Enzalutamide in patients with cancer castration resistant prostate cancer with the presence ofvisceral disease

Beneficio clinico, in termini di controllo di malattia a 3 mesi(DCR) di Enzalutamide in pazienti affetti da carcinoma della prostata metastatico resistente alla castrazione con presenza di malattia viscerale

E.2.2

Secondary objectives of the trial

Evaluate the safety profile of the treatment; Assess the quality of life through specific questionnaires such as EQ-5D-5L and FACT-P; Assess pain using the BPI-SF questionnaire

Valutare il profilo di tollerabilità del trattamento; Valutare la qualità di vita attraverso specifici questionari quali: EQ-5D-5L e FACT-P; Valutare il dolore mediante il questionario BPI-SF.

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

Pharmacogenetics
Version: 1
Date: 27/10/2015
Title: A phase II study evaluating the efficacy of enzalutamide and the role of ARv7 in metastatic castration resistant prostate cancer (mCRPC) patients with visceral disease
Objectives: To explore the association between AR-V7 splicing variants (in CTCs samples) and treatment response/resistance.

Farmacogenetica
Versione: 1
Data: 27/10/2015
Titolo: Studio di fase II per valutare l’efficacia di Enzalutamide e il ruolo di
ARv7 in pazienti affetti da carcinoma della prostata metastatico resistente alla castrazione con malattia viscerale.
Obiettivi: Verificare l’associazione tra la variante di splicing AR-V7 (determinatasui campioni di CTCs) e la risposta/resistenza al trattamento.

E.3

Principal inclusion criteria

- Biopsy (primary tumour or metastases) confirming the diagnosis of prostate adenocarcinoma
- Documented measurable metastatic visceral disease (according to RECIST 1.1 criteria)
- Life expectancy > 3 months
- Patients may have received previous therapy including chemotherapy (including docetaxel)
- Progressive disease by PSA or imaging in the setting of medical or surgical castration. Disease progression for study entry is defined as one or more of the following three criteria (according with PCWG2)

- Diagnosi istologica (tumore primitivo o metastasi) di adenocarcinoma della prostata
- Almeno 1 lesione viscerale metastatica misurabile
- Aspettativa di vita > 3 mesi
- pazienti devono avere ricevuto un trattamento precedente ed essere in fase di resistenza alla castrazione. Possono avere ricevuto un trattamento chemioterapico contenente Docetaxel
- Evolutività di malattia biochimica (PSA) e/o radiologica in accordo con i criteri PCWG2

E.4

Principal exclusion criteria

- Metastases in the brain or active epidural disease
- History of another malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer
- Prior treatment with abiraterone acetate
- Treatment (concomitant or in the previous 2 weeks) with anti-androgens (eg. Bicalutamide, nilutamide, flutamide) or 5-a reductase inhibitors (eg. finasteride, dutasteride)

- Metastasi cerebrali o meningee
- Anamnesi di seconda neoplasia maligna nei 5 anni precedenti eccetto che per tumori della pelle non melanoma trattati radicalmente
- Precedente trattamento con abiraterone
-Trattamento attuale o pregresso nelle 2 settimane precedenti l’inizio del trattamento con il medicinale sperimentale con uno dei seguenti agenti per il carcinoma della prostata: Antiandrogeni (es. bicalutamide, nilutamide, flutamide) Inibitori della 5-a reduttasi (es. finasteride, dutasteride)

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is 3 months DCR

L’endpoint primario è il controllo di malattia a 3 mesi

E.5.1.1

Timepoint(s) of evaluation of this end point

3 month

3 mesi

E.5.2

Secondary end point(s)

- To determine the safety of the treatment
- to evaluate quality of life according EQ-5D-5L e FACT-P
- to evaluate pain according to BPI-SF

- Valutare il profilo di tollerabilità del trattamento
- Valutare la qualità di vita attraverso specifici questionari quali: EQ-5D-5L e FACT-P
- Valutare il dolore mediante il questionario BPI-SF.

E.5.2.1

Timepoint(s) of evaluation of this end point

end of study

fine studio

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

To explore the association between AR-V7 splicing variants (in CTCs samples) and treatment response/resistance.

Verificare l’associazione tra la variante di splicing AR-V7 (determinata
sui campioni di CTCs) e la risposta/resistenza al trattamento

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

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

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:

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

F.4.2.2

In the whole clinical trial

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 standard of care in prectice at the investigator site

standard terapeutico utlizzato nella normale pratica clinica

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

2016-01-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-04-06

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-12-28

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