Clinical Trials Register

Summary
EudraCT Number:	2017-004332-11
Sponsor's Protocol Code Number:	P.64Cu.002.02
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2018-10-04
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

2017-004332-11

A.3

Full title of the trial

Use of 64CuCl2 PET/CT Imaging in the selection of patients with prostate cancer in biochemical relapse after prostatectomy, to be successfully treated with salvage radiotherapy on the prostatic bed

Utilizzo dell¿Imaging PET/CT con 64CuCl2 nella selezione dei pazienti con tumore della prostata in recidiva biochimica dopo prostatectomia, da trattare con successo con radioterapia di salvataggio sul letto prostatico

A.3.1

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

Use of the diagnostic PET with 64CuCl2 in order to select patients, in which a disease relapse is shown after prostate surgical removal, to be successfully treated to radiation therapy on the prostate bed

Uso della tecnica diagnostica PET con 64CuCl2 al fine di selezionare pazienti, in cui si ¿ manifestata una ripresa della malattia dopo la rimozione chirurgica della prostata, che risponderanno con successo alla radioterapia sul letto prostatico

A.3.2

Name or abbreviated title of the trial where available

64CuCl2 PET/CT for cancer on the prostatic bed

PET/CT con 64CuCl2 per tumore sul letto prostatico

A.4.1

Sponsor's protocol code number

P.64Cu.002.02

A.5.4

Other Identifiers

Name:

N.A.

Number:

N.A.

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	A.C.O.M. -ADVANCED CENTER ONCOLOGY MACERATA -S.R.L.
B.1.3.4	Country	Italy
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	Sparkle srl
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	Sparkle srl
B.5.2	Functional name of contact point	Project Manager
B.5.3	Address:
B.5.3.1	Street Address	localit¿ cavallino snc
B.5.3.2	Town/ city	montecosaro scalo
B.5.3.3	Post code	62010
B.5.3.4	Country	Italy
B.5.4	Telephone number	0733560354
B.5.5	Fax number	0733560352
B.5.6	E-mail	p.panichelli@sparklepet.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	No
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	64-Rame Cloruro
D.3.2	Product code	[64Cu(II)Cl2]
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	CLORURO DI RAME (Cu-64)
D.3.9.2	Current sponsor code	(64Cu)CuCl2
D.3.9.3	Other descriptive name	64-copper chloride
D.3.10	Strength
D.3.10.1	Concentration unit	Bq/ml becquerel(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	925000000
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

cancer on the prostatic bed

carcinoma su letto prostatico

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	20.0
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

The primary objective is to evaluate the diagnostic accuracy of PET with 64CuCl2 in the diagnosis of local recurrence (PSA> 0.2, <= 1ng / ml) of prostatic carcinoma after radical prostatectomy, in patients negative to traditional methods.

L¿obiettivo primario ¿ quello di valutare l¿accuratezza diagnostica della PET con 64CuCl2 nella diagnosi di recidiva locale (PSA> 0,2, <= 1ng / ml) di carcinoma prostatico dopo prostatectomia radicale, nei pazienti negativi alle metodiche tradizionali.

E.2.2

Secondary objectives of the trial

1. to evaluate the ability to detect relapse sites in subgroups with PSA <0.5 and between 0.5 and 1;
2. to evaluate the clinical impact (treatment modification) of cases with positive 64CuCl2-PET in lymph nodes or for distant metastases (M+);
3. to evaluate all the performance indicators of interest of the 64CuCl2-PET referring to the response after Salvage Radiotherapy
4. to estimate the median time to reach the minimum value (NADIR) of the PSA in B+ patients;
5. to evaluate the optimal SUV for the detection of index lesions in the prostate bed;
6. to evaluate the safety aspects and the surveillance of adverse events.

1. Valutare la capacit¿ di rilevare siti di recidiva nei sottogruppi con PSA <0.5 e compreso tra 0.5 e 1;
2. Valutare l¿impatto clinico (modificazione del trattamento) dei casi con 64CuCl2-PET positiva nei linfonodi o per metastasi a distanza (M+);
3. Valutare tutti gli indicatori di performance d¿interesse della 64CuCl2-PET facendo riferimento alla risposta dopo SRT;
4. Stima del tempo mediano al raggiungimento del valore minimo (NADIR) del PSA nei pazienti B+;
5. Valutare il SUV ottimale per l¿individuazione delle lesioni indice nel letto prostatico;
6. Valutare gli aspetti di sicurezza e la sorveglianza degli eventi avversi.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. >=45 years old at the moment of enrolment in the study
2. Previous documented histological diagnosis of primitive prostate adenocarcinoma
3. Prior radical prostatectomy surgery
4. Zeroing of the circulating PSA values
5. Presence of biochemical relapse documented by circulating PSA values raising in two consecutive determinations performed within three weeks of distance (values over 0.2ng / ml and lower than 1.1 ng /ml)
6. Absence of distant metastatic lesions not shown by previous mpMRI and PET / CT-18F-choline tests
7. Negative clinical history for other pre-existing or current neoplastic diseases, with the exception of non-melanoma skin cancers
8. Previous execution of 18F-FCH-PET not older than 30 days
9. Patients to be treated with rescue radiotherapy on the prostatic bed
10. Previous execution of mpMRI not older than 30 days
11. Karnofski’s Index = 80%
12. Absence of other relevant co-morbidities (see: exclusion criteria)
13. Full ability to understand the information in the informed consent sheet
14. Full ability to sign informed consent

1. Età>=45 anni al momento dell’arruolamento
2. Pregressa diagnosi istologica, documentabile, di adenocarcinoma primitivo della prostata
3. Pregresso intervento chirurgico di prostatectomia radicale
4. Azzeramento dei valori di PSA circolante
5. Presenza di recidiva biochimica documentata da innalzamento dei valori del PSA circolante in due determinazioni eseguite consecutivamente al massimo entro tre settimane di distanza (valori oltre i 0.2ng/ml ed inferiori a 1.1 ng/ml)
6. Assenza di lesioni metastatiche a distanza non evidenziabili da precedenti esami di mpMRI e PET/CT-18F-colina
7. Storia clinica negativa per altre patologie neoplastiche pregresse od in atto, con l’eccezione di carcinomi cutanei non-melanoma
8. Precedente esecuzione di 18F-FCH-PET non più vecchia di 30 giorni
9. Pazienti da trattare con radioterapia di salvataggio sul letto prostatico
10. Precedente esecuzione di mpMRI non più vecchia di 30 giorni
11. Indice di Karnofski = 80%
12. Assenza di altre comorbilità rilevanti (cfr: criteri di esclusione)
13. Piena capacità di comprendere le informazioni riportate nella documentazione illustrativa per il Soggetto
14. Piena capacità di sottoscrivere il consenso informato

E.4

Principal exclusion criteria

1. Anemia with Hb <9 gr / dl
2. Subject treated with ADT (orchiectomy, and / or LHRH agonists, and / or androgen antagonists)
3. Presence of symptoms or signs of sepsis and / or evidence of acute infections
4. AST> 1.5 times the upper limit of the normal range
5. ALT> 1.5 times the upper limit of the normal range
6. Total bilirubin> 1.5 times the upper limit of the normal range
7. Clinical history and / or previous serological evidence for HBV infection
8. Clinical history and / or previous serological evidence for HCV infection
9. copper metabolism diseases (Menkes’ disease, Wilson’s disease)
10. Subjects who have received chemotherapy in the previous 120 days
11. Radiotherapy performed in the previous 120 days
12. Major surgery performed in the previous 120 days
13. Presence of lesions in the prostatic bed evidenced by previous mpMRI and / or US examinations
14. Previous participation in clinical trials with exposure to ionizing radiation for therapeutic purposes
15. Any condition, material, logistics, or Subjective, which, even in the opinion of the Principal Investigator, may condition the subject's compliance with the execution of the procedures established by the Protocol
16. Inability to understand the contents of the information documentation for the subject

1. Anemia con Hb<9 gr/dl
2. Soggetto in trattamento con ADT (orchiectomia, e/o agonisti LHRH, e/o antagonisti degli androgeni)
3. Presenza di sintomi o segni di sepsi e/o evidenza di infezioni acute
4. AST >1.5 volte il limite superiore del range di normalità
5. ALT >1.5 volte il limite superiore del range di normalità
6. Bilirubina totale > 1.5 volte il limite superiore del range di normalità
7. Storia clinica e/o pregressa evidenza sierologica per infezione HBV
8. Storia clinica e/o pregressa evidenza sierologica per infezione HCV
9. Malattie del metabolismo del rame (m. di Menkes, m.di Wilson)
10. Soggetti che abbiano ricevuto Chemioterapia nei 120 gg precedenti
11. Radioterapia effettuata nei 120 gg precedenti
12. Chirurgia maggiore effettuata nei 120 gg precedenti
13. Presenza nel letto prostatico, di lesioni evidenziabili da precedenti esami di mpMRI e/o US
14. Precedente partecipazione a trials clinici con esposizione a radiazioni ionizzanti a scopo terapeutico
15. Qualsiasi condizione, materiale, logistica, o Soggettiva, che, anche a giudizio dello Sperimentatore Principale, possa condizionare la compliance del Soggetto alla esecuzione delle procedure previste dal Protocollo
16. Incapacità a comprendere il contenuto della documentazione informativa per il Soggetto

E.5 End points

E.5.1

Primary end point(s)

To evaluate the relationship between PSA levels (calculated between PSA levels measured before treatment and minimum PSA level measured during the observational period following the treatment) and prostatic bed (positive prostate (B +) and negative prostate (B-). The 64CuCl2-PET is obtained positive (B +) when in the prostate bed a detectable focal absorption is manifested because superior to the value of the background; otherwise it is judged negative (B-) The SRT response is defined as positive (R +) if a PSA decrease of =15% respect to the initial PSA value otherwise the SRT response is defined as negative (R -). It will be considered true positive patients (B+)(R+) and true negatives (B-)(R-).

Valutare la relazione tra la variazione percentuale di PSA (calcolata come differenza tra il valore PSA misurato prima del trattamento e il livello minimo di PSA misurato nei tempi di osservazione successivi all’inizio del trattamento) e il letto prostatico (letto prostatico positivo (B+) e letto prostatico negativo (B-). La 64CuCl2-PET viene valutata positiva (B+) quando nel letto prostatico si manifesta una uptake focale rilevabile perché superiore al valore del fondo; viene altrimenti giudicata negativa (B-) La risposta SRT viene definita come positiva (R+) se si verifica una diminuzione =15% del valore del PSA prima dell’inizio della SRT e valutata come negativa (R-) se non si verifica una diminuzione di almeno il 15%.
Verranno considerati VP (veri positivi) i casi (B+)(R+) e VN (veri negativi) i casi (B-)(R-).

E.5.1.1

Timepoint(s) of evaluation of this end point

5 weeks, 10 weeks and 4 months since the beginning of radiotherapy.

5 settimane, 10 settimane e 4 mesi dall'inizio della radioterapia

E.5.2

Secondary end point(s)

1) Calculation of the maximum variation of PSA in the subgroups of patients with PSA <0.5 and PSA between 0.5 and 1, through the ROC curve and evaluation of the ability to detect sites of recurrence
2) In each patient the impact that the positive results of 64CuCl2-PET out of the prostatic bed would have had on the therapeutic choice will be evaluated and tabulated, also taking into account the classification of the patient in R + / R-;
3) Sensitivity, specificity, positive and negative predictive values and area under the curve (AUC) will be evaluated.
4) The time between treatment beginning (baseline) and the achievement of the minimum value (NADIR) will be estimated through estimates of Kaplan-Meyer curves.
5) The SUV values of the prostate bed index lesions will be correlated with the actual SRT response, in order to identify the SUV limits below which the uptake is not significant
6) Adverse events will be recorded and classified according to the EMA guidelines.

1) Calcolo della variazione massima di PSA nei sottogruppi di pazienti con PSA<0.5 e PSA compreso tra 0.5 e 1, mediante la curva ROC e valutazione della capacit¿ di rilevare siti di recidiva
2) In ciascun paziente verr¿ valutato e tabulato l'impatto che avrebbe avuto sulla scelta terapeutica la presenza di risultati positivi della 64CuCl2-PET fuori del letto prostatico, anche tenendo conto della classificazione del paziente in R+/R-;
3) Verr¿ valutata sensibilit¿, specificit¿, valori predittivi positivi e negativi e area sotto la curva (AUC).
4) Verranno stimati i tempi che intercorrono tra l¿inizio del trattamento (basale) ed il raggiungimento del valore minimo (NADIR) mediante stime delle curve di Kaplan-Meyer.
5) Verranno correlati i valori dei SUV delle lesioni indice del letto prostatico con l¿effettiva risposta alla SRT, al fine di identificare i limiti di SUV al di sotto dei quali la captazione non ¿ significativa
6) Verranno registrati e classificati gli eventi avversi, secondo le direttive EMA.

E.5.2.1

Timepoint(s) of evaluation of this end point

at trial completion

a fine studio

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

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)

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

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

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

138

F.4.2

For a multinational trial

F.4.2.1

In the EEA

138

F.4.2.2

In the whole clinical trial

138

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)

according to routinary clinical practice

come da 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

2018-03-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-01-16

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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