Clinical Trials Register

Summary
EudraCT Number:	2020-004530-38
Sponsor's Protocol Code Number:	ASSTBS-FARONCO-PESETA-20
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:	2022-01-27
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

2020-004530-38

A.3

Full title of the trial

PROSPECTIVE, PHASE II STUDY TO EVALUATE THE EFFICACY OF ADDITION OF PROGESTERONE TO STANDARD CHEMOTHERAPY ACCORDING TO EDP SCHEME PLUS MITOTANE IN PATIENTS WITH ADVANCED ADRENALCORTICAL (PESETA TRIAL)

Studio prospettico, di fase II volto a valutare l’efficacia dell’aggiunta di progesterone alla chemioterapia standard secondo schema EDP + mitotane nei pazienti affetti da carcinoma della corticale del surrene avanzato.

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

PESETA

A.4.1

Sponsor's protocol code number

ASSTBS-FARONCO-PESETA-20

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	UNIVERSITA' DEGLI STUDI DI BRESCIA_ BANDO AIRC
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 SPEDALI CIVILI DI BRESCIA
B.5.2	Functional name of contact point	COORDINAMENTO RICERCA E STUDI DI FA
B.5.3	Address:
B.5.3.1	Street Address	PLE SPEDALI CIVILI 1
B.5.3.2	Town/ city	BRESCIA
B.5.3.3	Post code	25123
B.5.3.4	Country	Italy
B.5.4	Telephone number	0303996851
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	MEGACE - 160 MG COMPRESSE 30 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	PharmaSwiss Ceská republika s.r.o.
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	megace
D.3.2	Product code	[megace]
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	MEGESTROLO ACETATO
D.3.9.2	Current sponsor code	megestrolo
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	320
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

advanced/ metastatic patients with ACC

carcinoma della corticale del surrene avanzato

E.1.1.1

Medical condition in easily understood language

advanced/ metastatic patients with ACC

carcinoma della corticale del surrene avanzato

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 the combination regimen (EDP-M plus progesterone (EDP-MP)
versus EDP-M plus placebo) in advanced/ metastatic patients with ACC

Confrontare l’efficacia della chemioterapia etoposide+doxorubicina+ cisplatino con mitotane associata a:
progestinico (braccio A) o placebo (braccio B) in termini di response rate nei pazienti affetti da ACC
avanzato.

E.2.2

Secondary objectives of the trial

To evaluate the impact of the combination of the two treatments on hormone response
in patients with secreting ACC;
To assess the activity of the combination regimen on disease response assessed by the
CHOI criteria [15], and changes in Standardized Uptake Value (SUV) at FDG Positron
Emission Tomography (PET) scan;
- To compare the two treatment arms in terms of progression free survival (PFS);
- To compare the two treatment arms in terms of overall survival (OS);
- To evaluate the quality of life the quality of life by EORTC QLQ-C30;
- To evaluate the toxicity of the regimen.

Valutare l’effetto del trattamento di combinazione (EDP-M+progestinico) in termini di risposta
ormonale nei casi di ACC secernenti;
- Valutare l’effetto del trattamento di combinazione in termini di risposta considerando i criteri CHOI e le
modifiche del SUV (standardized untake value) nelle scansioni PET-TC;
- Confrontare i due trattamenti in termini di tempo libero da progressione (PFS);
- Confrontare i due trattamenti in termini di sopravvivenza globale (OS);
- Monitorare le modifiche percepite dal paziente in termini di qualità di vita (EORTC QOL-C30);
- Valutare la tossicità e gli eventi avversi, classificati secondo sistema NCI-CTAE (versione 5.0).

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: EVALUATION OF THE PROGNOSTIC IMPACT OF THE EXPRESSION OF KI67, CASPASI3,
NUCLEAR-CHAIN, IMMUNOLOGICAL PARAMETERS IN THE REMOVED RESIDUAL TUMOR
objectives:
THE PROGNOSTIC IMPACT OF THE EXPRESSION OF KI67, CASPASI3,
NUCLEAR-CHAIN, IMMUNOLOGICAL PARAMETERS

Altre tipologie di sottostudi
specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: VALUTAZIONE DELL’IMPATTO PROGNOSTICO DELL’ESPRESSIONE DI KI67, CASPASI3,
NUCLEAR -CATENINA, PARAMETRI IMMUNOLOGICI NEL TUMORE RESIDUO ASPORTATO.
Versione 1.0 del 17-05-2021
obiettivi
IMPATTO PROGNOSTICO DELL’ESPRESSIONE DI KI67, CASPASI3,
NUCLEAR -CATENINA, PARAMETRI IMMUNOLOGICI

E.3

Principal inclusion criteria

-Histologically confirmed diagnosis of ACC
- Locally advanced or metastatic disease not amenable to radical surgery resection
- ECOG performance status 0-2
- Effective contraception
- Life expectancy > 3 months
- Age > 18 years
- Adequate bone marrow reserve (neutrophils >1,000/mm3 and/or platelets >80,000/mm3) and organ function (including renal, liver and cardiac function)
- Be able to comply with the protocol procedures and provide written informed consent.

Diagnosi istologica di ACC;
- ACC in stadio III non operabile o stadio IV;
- Contraccezione adeguata;
- ECOG (performance status) 0-2;
- Età superiore ai 18 anni;
- Aspettativa di vita superiore ai 3 mesi;
- Adeguata riserva midollare (neutrofili > 1,000/mm3 e/o piastrine > 80,000/mm3);
- Buona funzionalità d’organo (comprendendo funzionalità renale, epatica e funzione cardiaca);
- Il paziente deve essere in grado di effettuare le procedure del protocollo e di fornire il consenso
informato in forma scritta.

E.4

Principal exclusion criteria

- History of recent or active prior malignancy, except for cured non-melanoma skin cancer,
cured in situ cervical carcinoma, breast ductal carcinoma in situ, or other treated
malignancies where there has been no evidence of disease for at least 2 years
-Renal insufficiency (estimated glomerular filtration rate [GFR]<50 mL/min/1.73 m2) or significant liver insufficiency (serum bilirubin>2 times the upper normal range and/or serum alanine aminotransferase [ALT] or aspartate aminotransferase [AST]>3 times the upper normal range). GFRs will be calculated according to the validated formula (MDRD)
- Pregnancy or breast feeding
- Congestive heart failure (ejection fraction<45%)
-Preexisting grade 2 peripheral neuropathy
- Previous or current treatment with mitotane or other antineoplastic drugs for ACC
- Previous radiotherapy for ACC

- Storia di recente o attiva neoplasia maligna primitiva, eccetto che si tratti di un tumore cutaneo
non-melanoma trattato ad intento curativo, carcinoma cervicale in situ trattato ad intento curativo,
carcinoma duttale in situ della mammella, od altri tumori maligni trattati senza evidenza di malattia
nei due anni successivi;
- Insufficienza renale (valore di filtrazione glomerulare [GFR] <50 mL/min/1.73m2) o
significativa insufficienza epatica (bilirubinemia > 2 volte il limite superiore del range di normalità e/o livelli ematici di alanina aminotransferasi [ALT] o aspartato aminotransferasi [AST] > 3 volte il
limite superiore del range di normalità). GFRs verrà calcolato con la formula concordata (MDRD);
- Gravidanza o allattamento;
- Scompenso cardiaco (Frazione di Eiezione < 45%);
- Neuropatia periferica di grado 2 preesistente;
- Pregressi trattamenti chemio-radioterapici per la neoplasia surrenalica;

E.5 End points

E.5.1

Primary end point(s)

Evaluation of efficacy
The following criteria will be used to assess treatment efficacy:
- RECIST Criteria 1.1 (see table below);
- Hormone response defined as 50% reduction of 24-h urinary free cortisol (UFC) excretion
within 1 month of treatment;
- CHOI Criteria (see table below);
- SUV variation: PERCIST Criteria (see table below).

Valutazione dell'efficacia:
criteri verranno utilizzati per valutare l'efficacia del trattamento:
- Criteri RECIST 1.1 (vedi tabella sotto);
- Risposta ormonale definita come riduzione del 50% dell'escrezione urinaria di cortisolo libero (UFC) nelle 24 ore
entro 1 mese dal trattamento;
- Criteri CHOI (vedi tabella sotto);
- Variante SUV: Criteri PERCIST

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 4 8 12 16 20 24 28
End of treatment visit (28days after last chemotherapy cycle)
Follow up visit (Every 12weeks for 1 year, t

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

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

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

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

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)

national health system (SSN)

in carico al Sistema Sanitario Nazionale (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

2022-05-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-01-11

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

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Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
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