Clinical Trials Register

Summary
EudraCT Number:	2016-000579-26
Sponsor's Protocol Code Number:	TRANSLATE-P
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:	2021-09-30
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

2016-000579-26

A.3

Full title of the trial

RESTORE IMMUNE COMPETENCE AGAINST CANCER CELLS IN PROSTATE CARCINOMA RESISTANT TO STANDARD TREATMENTS
TRANSLATE – prostate STUDY

ATTIVAZIONE DELLA RISPOSTA IMMUNITARIA IN PAZIENTI RESISTENTI AL TRATTAMENTO STANDARD - studio “TRANSLATE - prostata”

A.3.1

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

RESTORE IMMUNE COMPETENCE AGAINST CANCER CELLS IN PROSTATE CARCINOMA RESISTANT TO STANDARD TREATMENTS
TRANSLATE – prostate STUDY

ATTIVAZIONE DELLA RISPOSTA IMMUNITARIA IN PAZIENTI RESISTENTI AL TRATTAMENTO STANDARD - studio “TRANSLATE - prostata”

A.3.2

Name or abbreviated title of the trial where available

TRANSLATE-PROSTATE

TRANSLATE-PROSTATA

A.4.1

Sponsor's protocol code number

TRANSLATE-P

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	AZIENDA SANITARIA OSPEDALIERA S.CROCE E CARLE CUNEO
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	RETE ONCOLOGICA DEL PIEMONTE E VALLE D'AOSTA
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	AZIENDA OSPEDALIERA S. CROCE E CARLE DI CUNEO
B.5.2	Functional name of contact point	UFFICIO SPERIMENTAZIONI CLINICHE
B.5.3	Address:
B.5.3.1	Street Address	OSPEDALE CARLE - VIA ANTONIO CARLE, 25
B.5.3.2	Town/ city	CUNEO
B.5.3.3	Post code	12100
B.5.3.4	Country	Italy
B.5.4	Telephone number	00390171616738
B.5.5	Fax number	00390171616737
B.5.6	E-mail	trials@ospedale.cuneo.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	ENDOXAN BAXTER - 50 MG COMPRESSE RIVESTITE 50 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	BAXTER S.P.A.
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	Endoxan
D.3.4	Pharmaceutical form	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	CICLOFOSFAMIDE
D.3.9.2	Current sponsor code	na
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	50
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	PROLEUKIN - INIETTABILE 1 FLAC 18.000.000 UI 1 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	NOVARTIS FARMA S.P.A.
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	PROLEUKIN
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INTERLEUKINA 2 RECOMBINANT
D.3.9.2	Current sponsor code	NA
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1000000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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 castration resistant prostate carcinoma (mCRPC)

carcinoma della prostata metastatico resistente alla castrazione (mCRPC)

E.1.1.1

Medical condition in easily understood language

metastatic castration resistant prostate carcinoma (mCRPC)

carcinoma della prostata metastatico resistente alla castrazione (mCRPC)

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	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

Objective response rate

Tasso di risposte obiettive

E.2.2

Secondary objectives of the trial

Toxicity
QoL
Progression Free Survival (PFS)
Overall Survival (OS)

Tossicità
Valutazione della qualità di vita
Sopravvivenza libera da progressione (PFS)
Sopravvivenza globale (OS)

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

Other types of substudies
Specify title, date and version of each substudy with relative objectives: TRANSLATE - TRANSLATIONAL v. 1.0 08feb2016
Objectives

Analysis of changes of major circulating immunologic factors during the TRANSLATE study.
Analysis impact of the observed changes (if any) on the patients’ outcome.
Analysis of immunologic status at progression.

Altre tipologie di sottostudi
specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: TRANSLATE - TRANSLATIONAL v. 1.0 08/02/2016
Obiettivi

Analizzare le variazioni fra i maggiori fattori immunologici circolanti durante lo studio TRANSLATE.
Analizzare l’impatto dei cambiamenti osservati (se presenti) sull’outcome del paziente.
Analizzare lo stato immunitario alla progressione di malattia.

E.3

Principal inclusion criteria

- Hystologically confirmed mCRPC
- Metastatic disease previously treated with at least two lines of different systemic therapy.
- Measurable disease (RECIST criteria).
- At least one metastatic site suitable for irradiation.
- Signed informed consent.
- Geographical accessibility.
- Age >18 y.o.
- Karnofsky P.S. ¿ 60(attachment 1).
- Life expectancy > 3 months.
- Adequate bone marrow function (Absolut Neutrophil count ¿¿1,5 x 109/l, platelets ¿¿100 x 109/l, hemoglobin ¿¿10 g/dL).
- Adequate liver function: transaminases = 2.5 x upper limit of normality (ULN); bilirubin = 1.5 x ULN.
- Adequate renal function: Creatinine = ULN or creatinine clearance > 60 mL/min (Cockroft-Gault).
- Fertil men must be using adequate contraceptive measures throughout the study period and for up to 6 months after the last dose of study treatment if their partner are women of childbearing potential.
- Adequate cardiac function (LVEF ¿ 50% evacuate by MUGA Scan or Echocardiography) .

• Diagnosi istologica di carcinoma della prostata
• Malattia metastatica pretrattata con almeno due linee di trattamento sistemico
• Malattia misurabile secondo i criteri RECIST
• Almeno una sede di malattia metastatica suscettibile di trattamento radioterapico
• Consenso informato scritto
• Accessibilità geografica
• Età superiore ai 18 anni
• Karnofsky Performance Status > 60% (allegato 1)
• Aspettativa di vita > 3 mesi
• Adeguato profilo ematologico: conta assoluta dei neutrofili (ANC) ¿¿1,5 x 109/l, piastrine ¿¿100 x 109/l, emoglobina ¿¿10 g/dL.
• Adeguata funzionalità epatica: transaminasi ¿¿2,5 volte il limite superiore di normalità (ULN), bilirubina totale ¿¿1,5 volte l’ULN
• Adeguata funzionalità renale: creatinina sierica ¿¿ULN o clearance della creatinina calcolata (Cockroft-Gault) > 60 mL/min
• Gli uomini fertili, se le loro partner sono in età fertile, devono usare un metodo contraccettivo adeguato durante tutto lo studio e fino ad almeno 6 mesi dopo la sua interruzione
• Adeguata funzionalità cardiaca (frazione di eiezione > 50 %, valutata con MUGA scan o ecocardiogrammma)

E.4

Principal exclusion criteria

- History of malignant disease (with the exception of non-melanoma skin tumours) in the preceding five years.
- Prior organ transplantation.
- Brain metastasis.
- Autoimmune or allergic disorders.
- Prior treatment with IL-2.
- Previous HBV or HCV infections.
- Active steroid therapy.
- Any active infection requiring specific treatment (Antibiotics, antimicotic, antiviral).
- Radiotherapy within 6 weeks before enrollment.
- Other non-malignant uncontrolled systemic diseases or social conditions that would preclude trial entry in the opinion of the investigator.
- IL-2 treatment contraindications:
1. Hypersensitivity to the active ingredient or to any excipient.
2. Inadequate bone marrow function: WBC <2900 mm3 and/or HCT <30% and/or platelets count <90000 mm3.
3. Uncontrolled serous effusions (pleural, pericardic or peritoneal)
4. Blood Pressure <60 mmHg.
5. Pregnancy or breast feeding.
6. Active infections.
7. Brain metastases.
Cyclophosphamide treatment contraindications:
1. Cystitis.
2. Urinary Obstruction.
3. Inadequate bone marrow function: WBC <2900 mm3 and/or HCT <30% and/or platelets count <90000 mm3.
4. Active infections.
5. Pregnancy or breast feeding.

• Pregresse neoplasie maligne d'altra origine nei precedenti 5 anni (esclusi tumori della cute, non melanoma) .
• Trapianti d'organo
• Metastasi cerebrali
• Patologia autoimmune od allergica
• Pregresso trattamento con IL2
• Pregresse infezioni da HBV e/o HCV
• Trattamento attivo con cortisonici.
• Malattia infettiva in atto che necessita di terapia specifica (antibiotica, antimicotica o antivirale ).
• Radioterapia nelle 6 settimane precedenti l’arruolamento.
• Presenza di altra condizione non oncologica non controllata o condizioni sociali che precludano l’entrata in studio nell’opinione del clinico.
• Controindicazioni al trattamento con Interleukina-2:
1. Ipersensibilità ai principi attivi o a uno qualsiasi degli eccipienti.
2. Funzione midollare gravemente compromessa: globuli bianchi totali <2900 mmc e/o Ematocrito <30% e/o Piastrine <90000 mmc.
3. Versamenti sierosi non controllati (pleurici, pericardici, peritoneali).
4. Pressione arteriosa < 60 mmHg a riposo.
5. Gravidanza o allattamento.
6. Infezioni in atto.
7. Metastasi cerebrali note.
• Controindicazioni al trattamento con Ciclofosfamide:
1. Cistite.
2. Ostruzione flusso urinario.
3. Funzione midollare gravemente compromessa: globuli bianchi totali <2900 mmc e/o Ematocrito <30% e/o Piastrine <90000 mmc.
4. Infezioni in atto.
5. Gravidanza o allattamento.

E.5 End points

E.5.1

Primary end point(s)

Objective response rate

Tasso di risposte obiettive

E.5.1.1

Timepoint(s) of evaluation of this end point

during treatment

durante il trattamento

E.5.2

Secondary end point(s)

Toxicity; QoL; Progression Free Survival; Overall Survival

Tossicità; Valutazione della qualità di vita; sopravvivenza libera da progressione; sopravvivenza globale

E.5.2.1

Timepoint(s) of evaluation of this end point

during treatment and during 4 weeks after the end of treatment; every cycle and at the end of treatment; from study entry to first documented disease progressione or Death from any cause wichever occurred first; from study entry to Death from any cause

durante il trattamento e nelle 4 settimane successive al termine del trattamento; ad ogni ciclo e a fine trattamento; dall'entrata in studio al primo riscontro di progressione di malattia o morte per qualsivoglia causa; dall'entrata in studio alla morte per qualunque causa

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

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.8.3

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

Death of all enrolled patients

decesso di tutti i pazienti arruolati

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:

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)

follow-up until death

follow-up fino a decesso

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

2016-06-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-07-13

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

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