Clinical Trials Register

Summary
EudraCT Number:	2016-004452-29
Sponsor's Protocol Code Number:	IRST185.04
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2018-09-20
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

2016-004452-29

A.3

Full title of the trial

Randomized, multicentre phase II trial of the sequencing of Radium-223 and Docetaxel plus prednisone in symptomatic bone-only metastatic castration-resistant prostate cancer (mCRPC)

Studio randomizzato, multicentrico, di fase 2, di terapia sequenziale con radio-223 verso docetaxel più prednisone in pazienti affetti da carcinoma prostatico resistente alla castrazione con metastasi ossee sintomatiche

A.3.1

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

Randomized, multicentre phase II trial of the sequencing of Radium-223 and Docetaxel plus prednisone in symptomatic bone-only metastatic castration-resistant prostate cancer (mCRPC)

A.3.2

Name or abbreviated title of the trial where available

RAPSON

A.4.1

Sponsor's protocol code number

IRST185.04

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	ISTITUTO SCIENTIFICO ROMAGNOLO PER LO STUDIO E LA CURA DEI TUMORI (IRST) S.R.L. IRCCS
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	Bayer S.p.A.
B.4.2	Country	Italy
B.4.1	Name of organisation providing support	IRST IRCCS
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	IRST IRCCS
B.5.2	Functional name of contact point	Centro di Coordinamento Studi IRST
B.5.3	Address:
B.5.3.1	Street Address	Dipartimento di Oncologia ed Ematologia, Ospedale Civile S. Maria delle Croci, viale Randi, 5
B.5.3.2	Town/ city	Ravenna
B.5.3.3	Post code	48121
B.5.3.4	Country	Italy
B.5.4	Telephone number	0544285813
B.5.5	Fax number	0544285330
B.5.6	E-mail	cc.ubsc@irst.emr.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	DOCETAXEL ACCORD - 20 MG/1 ML - CONCENTRATO PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO - FLACONCINO (VETRO) - 1 ML 1 FLACONCINO
D.2.1.1.2	Name of the Marketing Authorisation holder	ACCORD HEALTHCARE LIMITED
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	DOCETAXEL_IRSTIRCCS
D.3.2	Product code	DOCETAXEL_IRSTIRCCS
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DOCETAXEL
D.3.9.1	CAS number	114977-28-5
D.3.9.2	Current sponsor code	DOCETAXEL_IRSTIRCCS
D.3.9.3	Other descriptive name	DOCETAXEL
D.3.9.4	EV Substance Code	SUB180674
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	75
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.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	XOFIGO - "1000 KBQ/ML SOLUZIONE INIETTABILE" USO ENDOVENOSO FLACONCINO IN VETRO 6.0 ML - 1 FLACONCINO
D.2.1.1.2	Name of the Marketing Authorisation holder	BAYER PHARMA AG
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	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	radium-223
D.3.9.1	CAS number	444811-40-9
D.3.9.2	Current sponsor code	RADIUM-223_IRSTIRCCS
D.3.9.4	EV Substance Code	SUB185095
D.3.10	Strength
D.3.10.1	Concentration unit	Bq/kg becquerel(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	55000
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	Yes
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

symptomatic bone-only metastatic castration-resistant prostate cancer

carcinoma prostatico resistente alla castrazione con metastasi ossee sintomatiche

E.1.1.1

Medical condition in easily understood language

symptomatic bone-only metastatic castration-resistant prostate cancer

carcinoma prostatico resistente alla castrazione con metastasi ossee sintomatiche

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10001186
E.1.2	Term	Adenocarcinoma of 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 the effects of sequential treatment between radium-223 and docetaxel on the percentage of symptomatic bone-only CRPC patients experiencing improvement or worsening in health-related quality of life (HRQoL).

identificazione del miglior trattamento sequenziale, in termini di miglioramento della qualità della vita, tra radio-223 e docetaxel, nei pazienti affetti da carcinoma prostatico resistente alla castrazione con metastasi ossee sintomatiche

E.2.2

Secondary objectives of the trial

To compare survival in patients treated with sequential therapy between radium-223 and docetaxel and to identify predictive factors of Radium-223 for clinical outcome in this patient population.

Impatto sull’outcome clinico e sulla sopravvivenza ed identificazione di fattori predittivi e prognostici

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients must have histologically or cytologically confirmed adenocarcinoma of prostate
2. Two or more bone metastases confirmed by bone scintigraphy within 4 weeks prior to study entry
3. Known castration-resistant disease, defined according to PCWG3 criteria as: castrate serum testosterone level: ≤50 ng/dL (≤1.73 nmol/L)
4. Subjects who have failed initial hormonal therapy, either by orchiectomy or by using a GnRH agonist in combination with an anti-androgen, must first progress through antiandrogen withdrawal prior to being eligible. The minimum timeframe to document failure of anti-androgen withdrawal will be four weeks
5. Progressive disease based on PSA and/or radiographic criteria
6. ECOG performance status ≤2

1. Pazienti con diagnosi istologica o citologica di carcinoma della prostata
2. Due o più metastasi ossee identificate alla scintigrafia ossea ed assenza di metastasi viscerali
3. Progressione di malattia basata su un inequivocabile aumento del PSA e/o criteri radiografici
4. Malattia resistente alla castrazione, secondo i criteri PCWG3 per cui livelli di testosterone devono essere ≤50 ng/dL (≤1.73 nmol/L)
5. Pazienti che abbiano fallito un trattamento ormonale qualsiasi, incluso anche abiraterone e/o enzalutamide, che deve essere terminato almeno 4 settimane prima di entrare nello studio
6. ECOG performance status ≤2

E.4

Principal exclusion criteria

1. Patients who have had previous chemotherapy.
2. Patients who have had radiotherapy within 4 weeks prior to entering the study.

1. Pazienti che non abbiano ricevuto una precedente chemioterapia
2. Pazienti che non abbiano ricevuto una precedente radioterapia entro 4 settimane dall’inizio dello studio

E.5 End points

E.5.1

Primary end point(s)

QoL clinical benefit

Qualità della vita

E.5.1.1

Timepoint(s) of evaluation of this end point

36 months

36 mesi

E.5.2

Secondary end point(s)

1) Progression-free survival (PFS)
2) Total progression-free survival (TPFS)
3) Overall survival (OS)
4) Safety
5) Identification of markers predictive to clinical outcome

1) Sopravvivenza libera da progressione (PFS)
2) Sopravvivenza totale libera da progressione (TPFS)
3) Sopravvivenza globale (OS)
4) Sicurezza
5) Identificazione di fattori predittivi dell'outcome clinico

E.5.2.1

Timepoint(s) of evaluation of this end point

1) 36 months
2) 36 months
3) 36 months
4) 36 months
5) 36 months

1) 36 mesi
2) 36 mesi
3) 36 mesi
4) 36 mesi
5) 36 mesi

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

Identification of markers predictive to clinical outcome

Identificazione di fattori predittivi dell'outcome clinico

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

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

terapia sequenziale con radio-223 verso docetaxel

sequencing therapy with radio-223 vs docetaxel

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.8.5.1

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

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

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

Information not present in EudraCT

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

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

Information not present in EudraCT

F.3.3.2

Women of child-bearing potential using contraception

Information not present in EudraCT

F.3.3.3

Pregnant women

Information not present in EudraCT

F.3.3.4

Nursing women

Information not present in EudraCT

F.3.3.5

Emergency situation

Information not present in EudraCT

F.3.3.6

Subjects incapable of giving consent personally

Information not present in EudraCT

F.3.3.7

Others

Information not present in EudraCT

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)

Follow-up assessments will be performed 3 and 6 months after the end of each treatment and at disease progression: clinical examination, blood test, chest, abdominal, pelvic and bone scans and quality of life questionnaires.

Le visite di follow-up sono schedulate a 3 e 6 mesi dopo la fine di ciascun trattamento ed al momento dell’eventuale progressione della malattia: visita clinica, prelievo di sangue, scansioni toraciche, addominali pelviche ed ossee, e questionari sulla qualità della vita.

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

2017-03-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-04-12

P. End of Trial
P.	End of Trial Status	Ongoing

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