Clinical Trials Register

Summary
EudraCT Number:	2016-000945-29
Sponsor's Protocol Code Number:	ASSTBS-ONCO-ABACUS-16
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:	2020-11-04
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

2016-000945-29

A.3

Full title of the trial

Activity of Abiraterone Acetate in the management of Cushing’s syndrome in patients with adrenocortical carcinoma (ABACUS)

Attività di Abiraterone nel trattamento della sindrome di Cushing in pazienti con carcinoma corticosurrenalico (ACC)

A.3.1

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

Activity of Abiraterone Acetate in the management of Cushing’s syndrome in patients with adrenocortical carcinoma (ABACUS)

Attività di Abiraterone nel trattamento della sindrome di Cushing in pazienti con carcinoma corticosurrenalico (ACC)

A.3.2

Name or abbreviated title of the trial where available

ABACUS

A.4.1

Sponsor's protocol code number

ASSTBS-ONCO-ABACUS-16

A.5.4

Other Identifiers

Name:

ABACUS

Number:

ASSTBS-ONCO-ABACUS-16

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 SOCIO SANITARIA TERRITORIALE DEGLI SPEDALI CIVILI DI BRESCIA
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	JansennCilag
B.4.2	Country	Italy
B.4.1	Name of organisation providing support	Università degli studi d iTorino- Polizza Assicura
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	ASST SPEDALICIVILI DI BRESCAI
B.5.2	Functional name of contact point	COORDINAMENTO RICERCA CLINICA
B.5.3	Address:
B.5.3.1	Street Address	P.LE SPEDALICIVILI 1
B.5.3.2	Town/ city	BRESCIA
B.5.3.3	Post code	25124
B.5.3.4	Country	Italy
B.5.4	Telephone number	0303996851
B.5.5	Fax number	0303996125
B.5.6	E-mail	coordinamento.ricerca@asst-spedalicivili.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	ZYTIGA - 250 MG - COMPRESSA - USO ORALE - FLACONE 120 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	JANSSEN-CILAG INTERNATIONAL N.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	ZYTIGA
D.3.2	Product code	[ZYTIGA]
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 acetato
D.3.9.1	CAS number	154229-18-2
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	1000
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

Cushing’s syndrome in patients with adrenocortical carcinoma

sindrome di Cushing in pazienti con carcinoma corticosurrenalico

E.1.1.1

Medical condition in easily understood language

Cushing’s syndrome in patients with adrenocortical carcinoma

sindrome di Cushing in pazienti con carcinoma corticosurrenalico (ACC)

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	10001388
E.1.2	Term	Adrenocortical carcinoma
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 assess the activity of AA in attaining normalization of 24-h urinary free cortisol (UFC) excretion relative to baseline within 1 month from treatment start;

: valutare l’attività di Abiraterone nell’indurre la normalizzazione dell’escrezione nelle 24 ore del cortisolo libero urinario (24-h UFC) rispetto al valore basale dopo 1 mese di trattamento;

E.2.2

Secondary objectives of the trial

to assess the activity of AA in attaining 50% reduction of 24-h UFC excretion within 1 month of treatment; - time to reduction of UFC; time to reduction of UFC; - effect of AA on levels of serum cortisol, UFC, midnight salivary cortisol, ACTH, aldosterone, PRA, DHEA-S, total testosterone, and steroid precursors; - improvement of the clinical signs associated to hypercortisolism as evaluated by a multiparameter scoring based on clinical signs/and symptoms (blood pressure, facial plethora, buffalo hump, supraclavicular fullness, hirsutism, striae rubrae, myopathy, depression) and biochemical alterations associated to hypercortisolism

valutare l’attività di Abiraterone nell’indurre una riduzione del 50% dell’escrezione di 24-h UFC excretion entro 1 mese di trattamento; - tempo necessario alla riduzione del 24-h UFC; - effetto di Abiraterone sui livelli sierici di cortisolo, UFC, cortisolo salivare midnight, ACTH, aldosterone, PRA, DHEA-S, testosterone totale e precursori steroidei in termini di variazione percentuale rispetto al baseline; - miglioramento dei segni clinici associate all’ipercortisolismo valutato da un sistema multiparametrico basato su segni e sintomi clinici (pressione arteriosa, plethora facciale, gibbo bufalino, imbottimento sopraclavicolare, irsutismo, striae rubrae, miopatia, depression) ed alterazioni biochimiche associate all’ipercortisolismo

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Histologically-confirmed diagnosis of ACC
• CT or MRI evidence of metastatic or locally advanced ACC (ENSAT stage III-IV) unsuitable for radical surgery
• Age = 18 years
• Confirmed diagnosis of Cushing’s syndrome validated by:
- two 24 h urinary collections for UFC at least 1.5 times the upper the normal levels, within 2 weeks prior to enrollment;
- serum ACTH levels lower than the normal range;
• ECOG performance status = 2
• Effective contraception

• Diagnosi di ACC istologicamente confermata
• ACC metastatico o localmente avanzato in base a CT or MRI (stadio ENSAT III-IV) non suscettibile di chirurgia radicale
• Età = 18 anni
• Diagnosi confermata di syndrome di Cushing validate da:
- due raccolte di urine delle 24 ore per UFC con valori almeno di 1,5 volte al di sopra dei valori di normalità, entro 2 settimane dall’arruolamento;
- livelli sierici di ACTH inferori al range di normalità;
• ECOG performance status = 2
• Effective contraception

E.4

Principal exclusion criteria

• Life expectancy less than 3 months
• Liver disease, such as cirrhosis, chronic or persistent active hepatitis or AST/ALT > 2 x ULN, bilirubin >2 x ULN
• Heart failure (NYHA class III or IV), unstable angina, severe arrhythmia or clinically significant impairment of heart function
• Major surgical procedure within one month prior entering the study
• Renal impairment (creatinine clearance < 40 ml/min).
• WBC <3 x 109 /L; Hb <13 g/dL for men and <12 g/dL for women; platelets <100 x 109 /L
• Any other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
• Pregnant or breast-feeding women
• History of alcohol or drug abuse
• History of recent or active prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other treated malignancies with no evidence of disease for at least three years)
• Acute or chronic uncontrolled infections
• Patient non-compliance

• Aspettativa di vita < 3 mesi
• Epatopatie come cirrosi, epatite cronica o attiva persistente o AST/ALT > 2 x ULN, bilirubina >2 x ULN
• Insufficienza cardiaca (classe NYHA III o IV), angina instabile, aritmia grave o alterazione clinicamente significativa della funzione cardiaca
• Interventi di chirurgia maggiore entro 1 mese prima dell’arruolamento nello studio
• Insufficienza renale (clearance creatinina < 40 ml/min).
• Leucociti <3 x 109 /L; Hb <13 g/dL per gli uomini e <12 g/dL per le donne; piastrine <100 x 109 /L
• Ogni altra condizione medica grave acuta o cronica o disordine psichiatrico o alterazione di laboratorio che rappresenterebbe , a giudizio dello sperimentatore, un rischio eccessivo alla partecipazione allo studio, alla somministrazione del farmaco in studio, o che, a giudizo dello sperimentatore, renderebbe il paziente ineleggibile alla partecipazione a questo studio
• Donne in gravidanza o in allattamento
• Storia di abuso alcolico e di droghe
• Anamnesi recente di una neoplasia o neoplasia attiva, ad eccezione dei tumori cutanei non-melanoma trattati, carcinoma della cervice uterine in situ trattato o altre neoplasie trattate senza evidenza di malattia attiva per almeno 3 anni.
• Infezioni acute o croniche non controllate
• Mancanza di compliance del paziente

E.5 End points

E.5.1

Primary end point(s)

to assess the activity of AA in attaining normalization of 24-h urinary free cortisol (UFC) excretion relative to baseline within 1 month from treatment start;

: valutare l’attività di Abiraterone nell’indurre la normalizzazione dell’escrezione nelle 24 ore del cortisolo libero urinario (24-h UFC) rispetto al valore basale dopo 1 mese di trattamento;

E.5.1.1

Timepoint(s) of evaluation of this end point

1 month from treatment start

1 mese di trattamento

E.5.2

Secondary end point(s)

1 mese di trattamento; - time to reduction of UFC; time to reduction of UFC; - effect of AA on levels of serum cortisol, UFC, midnight salivary cortisol, ACTH, aldosterone, PRA, DHEA-S, total testosterone, and steroid precursors; - improvement of the clinical signs associated to hypercortisolism as evaluated by a multiparameter scoring based on clinical signs/and symptoms (blood pressure, facial plethora, buffalo hump, supraclavicular fullness, hirsutism, striae rubrae, myopathy, depression) and biochemical alterations associated to hypercortisolism (hyperglycemia, Homa index, hypokalemia, dyslipidemia); - improvement of quality of life, based on validated questionnaire (FACT-G); - safety and tolerability of oral assumption of AA; - treatment response (according to RECIST criteria); - progression-free survival (defined as the time elapsing from patient registration and disease progression); - time to syndrome relapse (defined as the time elapsing from the best syndrome control within the first month to relapse of syndrome defined as: 1) Cushing symptoms recurrence; 2) increase more than 50% of nadir cortisol levels); - overall survival.; Pharmacokinetic

valutare l’attività di Abiraterone nell’indurre una riduzione del 50% dell’escrezione di 24-h UFC excretion ; ; effetto di Abiraterone sui livelli sierici di cortisolo, UFC, cortisolo salivare midnight, ACTH, aldosterone, PRA, DHEA-S, testosterone totale e precursori steroidei in termini di variazione percentuale rispetto al baseline; miglioramento dei segni clinici associate all’ipercortisolismo valutato da un sistema multiparametrico basato su segni e sintomi clinici (pressione arteriosa, plethora facciale, gibbo bufalino, imbottimento sopraclavicolare, irsutismo, striae rubrae, miopatia, depression) ed alterazioni biochimiche associate all’ipercortisolismo (hiperglicemia, Homa index, hipokaliemia, dislipidemia); - miglioramento della qualità di vita basato su questionari validati; - sicurezza e tollerabilità dell’assunzione orale di Abiraterone; - risposta obiettiva al trattamento (secondo criteri RECIST); - sopravvivenza libera da progressione (definite come tempo trascorso dalla registrazione del paziente alla progressione di ACC); - tempo alla recidiva della syndrome di Cushing (definite come tempo trascorso dal miglior controllo sindromico nel primo mese alla recidiva della syndrome definite come: 1) ripresa dei sintomi della sindrome di Cushing; 2) incremento di oltre il 50% del nadir dei livelli di cortisolo); - sopravvivenza globale.; analisi farmacocinetiche

E.5.2.1

Timepoint(s) of evaluation of this end point

1 month of treatment; ; at any time of followup; at any time of followup; T0: 4 weeks T1: 6 weeks T2: 8 weeks T3: 10 weeks T4: 12 weeks T5: 14 weeks T6: 16 weeks

to assess the activity of AA in attaining 50% reduction of 24-h UFC excretion within 1 month of treatment; ; a qualunque punto di followup; a qualunque punto di followup; T0: 4 weeks T1: 6 weeks T2: 8 weeks T3: 10 weeks T4: 12 weeks T5: 14 weeks T6: 16 weeks

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

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

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.8.2.4

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

Yes

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

Yes

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)

at the end of the study patients will be treated according to the programs covered by the
national health system

al termine dello studio i pazienti saranno trattati secondo i programmi previsti dal SSN

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

2016-06-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-04-19

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

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