Clinical Trials Register

Summary
EudraCT Number:	2020-001824-33
Sponsor's Protocol Code Number:	EFC15935
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-06-15
Trial results	View 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

2020-001824-33

A.3

Full title of the trial

A randomized, multicenter, double-blind phase 3 study of amcenestrant (SAR439859) plus palbociclib versus letrozole plus palbociclib for the treatment of patients with ER (+), HER2 (-) breast cancer who have not received prior systemic anti-cancer treatment for advanced disease

Studio di fase 3, randomizzato, multicentrico, in doppio cieco su amcenestrant (SAR439859) in associazione a palbociclib rispetto a letrozolo in associazione a palbociclib per il trattamento di pazienti con carcinoma mammario ER(+), HER2(-) che non hanno ricevuto una precedente terapia sistemica antitumorale per la loro malattia in stadio avanzato

A.3.1

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

Amcenestrant (SAR439859) plus palbociclib as first line therapy for patients with ER(+) HER2(-) advanced breast cancer

Amcenestrant (SAR439859) in associazione a palbociclib come terapia di prima linea per pazienti con carcinoma mammario avanzato ER(+) HER2(-)

A.3.2

Name or abbreviated title of the trial where available

AMEERA-5

A.4.1

Sponsor's protocol code number

EFC15935

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04478266

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1233-0486

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	SANOFI-AVENTIS RECHERCHE E DEVELOPPEMENT
B.1.3.4	Country	France
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	Sanofi-Aventis Recherche & Développement
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	SANOFI S.p.A.
B.5.2	Functional name of contact point	Contact Point
B.5.3	Address:
B.5.3.1	Street Address	Viale Luigi Bodio 37/B
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20158
B.5.3.4	Country	Italy
B.5.4	Telephone number	800226343
B.5.5	Fax number	0239394168
B.5.6	E-mail	informazioni.medicoscientifiche@sanofi.com

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	amcenestrant
D.3.2	Product code	[SAR439859]
D.3.4	Pharmaceutical form	Film-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	amcenestrant
D.3.9.2	Current sponsor code	SAR439859
D.3.9.4	EV Substance Code	SUB186740
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	200
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	Ibrance® 75 mg compressa rivestita con film
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Europe MA EEIG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Palbociclib
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Film-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	PALBOCICLIB
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	PALBOCICLIB
D.3.9.4	EV Substance Code	SUB177204
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	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: 3
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	Ibrance® 100 mg compressa rivestita con film
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Europe MA EEIG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Palbociclib
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Film-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	PALBOCICLIB
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	PALBOCICLIB
D.3.9.4	EV Substance Code	SUB177204
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	100
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: 4
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	Ibrance® 125 mg compressa rivestita con film
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Europe MA EEIG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Palbociclib
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Film-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	PALBOCICLIB
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	PALBOCICLIB
D.3.9.4	EV Substance Code	SUB177204
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	125
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: 5
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	Ibrance® 75 mg capsula rigida
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Europe MA EEIG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Palbociclib
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Capsule, hard
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	PALBOCICLIB
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	PALBOCICLIB
D.3.9.4	EV Substance Code	SUB177204
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	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: 6
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	Ibrance® 100 mg capsula rigida
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Europe MA EEIG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Palbociclib
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Capsule, hard
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	PALBOCICLIB
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	PALBOCICLIB
D.3.9.4	EV Substance Code	SUB177204
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	100
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: 7
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	Ibrance® 125 mg capsula rigida
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Europe MA EEIG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Palbociclib
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Capsule, hard
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	PALBOCICLIB
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	PALBOCICLIB
D.3.9.4	EV Substance Code	SUB177204
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	125
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: 8
D.1.2 and D.1.3	IMP Role	Comparator
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	Femara® 2.5 mg compresse rivestite con film
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Pharma GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Letrozole
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Capsule
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	LETROZOLO
D.3.9.1	CAS number	112809-51-5
D.3.9.2	Current sponsor code	NA
D.3.9.4	EV Substance Code	SUB08444MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2500
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: 9
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.2.1.2	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	GOSERELIN
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Implant
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	GOSERELIN ACETATO
D.3.9.2	Current sponsor code	NA
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3600
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	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
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

ER (+), HER2 (-) breast cancer

Carcinoma mammario ER(+), HER2(-)

E.1.1.1

Medical condition in easily understood language

Breast cancer

Carcinoma mammario

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	10006187
E.1.2	Term	Breast cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10028997
E.1.2	Term	Neoplasm malignant
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 determine whether Amcenestrant (SAR439859) in combination with palbociclib improves progression free survival (PFS) when compared with letrozole in combination with palbociclib in participants with ER+, HER2- advanced breast cancer who have not received any prior systemic anticancer therapies for advanced disease

Determinare se Amcenestrant (SAR439859) in associazione a palbociclib migliora la sopravvivenza libera da progressione (PFS) rispetto a letrozolo in associazione a palbociclib in partecipanti con carcinoma mammario avanzato ER+, HER2- che non hanno ricevuto una precedente terapia sistemica antitumorale per la malattia in stadio avanzato.

E.2.2

Secondary objectives of the trial

-To compare the overall survival in both treatment arms
-To evaluate the objective response rate in both treatment arms
-To evaluate the duration of response in both treatment arms
-To evaluate the clinical benefit rate in both treatment arms
-To evaluate progression-free survival on next line of therapy
-To evaluate the pharmacokinetics of amcenestrant, and palbociclib
-To evaluate health-related quality of life in both treatment arms
-To evaluate the time to first chemotherapy in both treatment arms
-To evaluate safety in both treatment arms

- confrontare la sopravvivenza globale in entrambi i bracci di trattamento
- valutare il tasso di risposta obiettiva in entrambi i bracci di trattamento
- valutare la durata della risposta in entrambi i bracci di trattamento
- valutare il tasso di beneficio clinico in entrambi i bracci di trattamento
- Valutare la sopravvivenza libera da progressione nella linea terapeutica successiva
- valutare la farmacocinetica di amcenestrant, e palbociclib
- valutare la qualità della vita correlata alla salute in entrambi i bracci di trattamento
- valutare il tempo intercorrente alla prima chemioterapia in entrambi i bracci di trattamento
- valutare la sicurezza in entrambi i bracci di trattamento

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Adult participants with loco-regional recurrent or metastatic disease not amenable to curative treatment
-Confirmed diagnosis of ER+/HER2- breast cancer
-No prior systemic treatment for loco-regional recurrent or metastatic disease
-Measurable disease evaluable per Response Evaluation Criterion in Solid Tumors (RECIST) v.1.1 or non-measurable bone-only disease
-Eastern Cooperative Oncology Group (ECOG) performance status 0-2
-Participants should be willing to provide tumor tissue
-Capable of giving informed consent

-Partecipanti adulti con malattia loco-regionale ricorrente o metastatica non suscettibile a trattamento curativo
-Diagnosi confermata di carcinoma mammario ER + / HER2-
-Nessuna precedente terapia sistemica per la malattia loco-regionale ricorrente o metastatica
- Malattia misurabile valutabile secondo i criteri RECIST v.1.1, o malattia ossea non misurabile.
- Stato di funzionalità 0-2 secondo l’Eastern Cooperative Oncology Group (ECOG).
- I partecipanti devono essere disponibili a fornire tessuto tumorale
- In grado di fornire il consenso informato

E.4

Principal exclusion criteria

-Known active brain metastases
-Prior neo (adjuvant) treatment with any selective estrogen receptor degrader (SERD)
-Inadequate organ and marrow function
-Disease recurrence while on, or within 12 months of completion of (neo)adjuvant endocrine therapy
-Pregnant, breastfeeding, or woman of child bearing potential unwilling to use recommended contraception methods
-Male participants who disagree to follow contraception
-Participants with advanced, symptomatic visceral spread, that are at risk of life-threatening complications in the short term
-Participants with significant concomitant illness

- metastasi cerebrali attive note
-Precedente trattamento (neo) adiuvante con un altro degradatore selettivo del recettore degli estrogeni (SERD)
-Inadeguata funzionalità d’organo e midollare
- Recidiva della malattia durante o entro 12 mesi dal completamento della terapia endocrina (neo)adiuvante
- Gravidanza, allattamento o donna in età fertile non disposte a utilizzare i metodi contraccettivi raccomandati
-Partecipanti di sesso maschile che non sono accettano di praticare contraccezione
-Partecipanti con diffusione viscerale sintomatica avanzata, che sono a rischio di complicanze pericolose per la vita nel breve termine
-Partecipanti con malattia significativa concomitante

E.5 End points

E.5.1

Primary end point(s)

Progression-free survival. Progression-free survival is defined as the time interval from the date of randomization to the date of first documented tumor progression as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or death (due to any cause), whichever come first

Sopravvivenza libera da progressione. La sopravvivenza libera da progressione è definita come l'intervallo di tempo dalla data della randomizzazione alla data della prima progressione documentata del tumore secondo i Criteri di valutazione della risposta nei tumori solidi (RECIST 1.1) o del decesso (da qualsiasi causa), a seconda di quale evento si verifichi per primo

E.5.1.1

Timepoint(s) of evaluation of this end point

From randomization date to date of first documentation of progression OR death (up to approximately 4 years)

Dalla data della randomizzazione alla data della prima progressione documentata O del decesso (fino a circa 4 anni)

E.5.2

Secondary end point(s)

1. Overall Survival. Overall survival is defined as the time interval from the date of randomization to the date of documented death (due to any cause).
2. Objective Response Rate. Objective response rate is defined as the proportion of participants who have a CR or PR, as best overall response determined as per RECIST 1.1, from the date of randomization to the date of until disease progression, death, cutoff date, initiation of posttreatment anti-cancer therapy, whichever occurs first.
3. Duration of Response. Duration of response is defined as the time from first documented evidence of CR or PR until progressive disease (PD) as determined as per RECIST 1.1 or death from any cause, whichever occurs first.
4. Clinical Benefit Rate. Clinical benefit rate is defined as the proportion of participants who have a confirmed CR, PR, or SD for at least 24 weeks determined as per RECIST 1.1, from the date of randomization until disease progression, death, cutoff date, initiation of post-treatment anticancer therapy, whichever occurs first.
5. PK parameter: Plasma concentrations. Plasma concentrations of Amcenestrant and palbociclib.
6. Number of participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs). Incidence of participants with TEAEs, SAEs and laboratory abnormalities according to NCI CTCAE V5.
7. Time to First Chemotherapy. Time to chemotherapy is defined as the time interval from the date of randomization to the start date of the first chemotherapy after study treatment discontinuation.
8. Health state utility and health status will be assessed using the European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L). Change From Baseline between treatment comparison Using the European Quality of Life- 5-Dimension 5 Level (EQ-5D 5L).
9. Disease-specific HRQL will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30). Change From Baseline between treatment comparison in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30).
10. Disease- and treatment-related quality of life will be assessed using the EORTC breast cancer module (QLQ-BR45) questionnaire. Change From Baseline between treatment comparison in Quality of Life Using the EORTC QLQ-BR45 (Breast) Questionnaire.
11. Disease- and treatment-related quality of life will be assessed using the EORTC breast cancer module (QLQ-BR23) questionnaire. Change From Baseline between treatment comparison in Quality of Life Using the EORTC QLQ-BR23 (Breast) Questionnaire.
12.Progression-free survival on next line of therapy (PFS2): PFS2 is defined as the time from the date of randomization to the date of first documentation of PD on the next systemic anti-cancer therapy according to investigator or death due to any cause, whichever occurs first.

1. Sopravvivenza globale. La sopravvivenza globale è definita come l'intervallo di tempo dalla data della randomizzazione alla data di decesso documentato (per qualsiasi causa).
2. Tasso di risposta obiettiva. Il tasso di risposta obiettiva è definito come la percentuale di partecipanti che presentano una CR o PR, come migliore risposta complessiva determinata secondo i criteri RECIST 1.1, dalla data della randomizzazione alla progressione della malattia, al decesso, alla data di cut-off, all’inizio della terapia antitumorale post-trattamento, a seconda di quale evento si verifichi per primo.
3. Durata della risposta. La durata della risposta è definita come il tempo dalla prima evidenza documentata di CR o PR fino alla malattia progressiva (PD) come determinato secondo i criteri RECIST 1.1 o al decesso da qualsiasi causa, a seconda di quale evento si verifichi per primo.
4. Tasso di beneficio clinico. Il tasso di beneficio clinico è definito come la percentuale di partecipanti che presentano una CR, PR o SD confermata per almeno 24 settimane determinata secondo i criteri RECIST 1.1, dalla data di randomizzazione alla progressione della malattia, al decesso, alla data di cut-off, all’inizio della terapia antitumorale post-trattamento, a seconda di quale evento si verifichi per primo.
5. Parametro PK: concentrazioni plasmatiche. Concentrazioni plasmatiche di Amcenestrant e palbociclib.
6. Numero di partecipanti con eventi avversi emergenti dal trattamento (TEAE) ed eventi avversi seri (SAE). Incidenza dei partecipanti con TEAE, SAE e anomalie di laboratorio secondo NCI CTCAE V5.
7. Tempo alla prima chemioterapia. Il tempo intercorrente alla chemioterapia è definito come l'intervallo di tempo dalla data di randomizzazione alla data di inizio della prima chemioterapia dopo l'interruzione del trattamento dello studio
8. L'utilità dello stato di salute e lo stato di salute saranno misurati utilizzando il questionario sulla qualità della vita EORTC, a 5 dimensioni e 5 livelli per dimensione (EQ-5D-5L). Confronto della variazione rispetto al basale tra i trattamenti utilizzando il questionario a 5 dimensioni - 5 livelli (EQ-5D-5L)
9. L'HRQL specifica per la malattia sarà valutata utilizzando il questionario di base sulla qualità della vita (QLQ-C30) dell'EORTC. Confronto della variazione rispetto al basale tra i trattamenti in termini di qualità della vita utilizzando il Questionario- Core 30 dell' EORTC (EORTC QLQ-C30).
10. La qualità della vita correlata alla malattia e al trattamento sarà valutata utilizzando il modulo specifico per il carcinoma mammario del questionario EORTC (QLQBR45). Confronto della variazione rispetto al basale tra i trattamenti in termini di qualità della vita utilizzando il questionario EORTC QLQ-BR45 (breast).
11. La qualità della vita correlata alla malattie e al trattamento sarà valutata utilizzando il modulo specifico per il carcinoma mammario del questionario EORTC (QLQBR23). Confronto della variazione rispetto al basale tra i trattamenti in termini di qualità della vita utilizzando il questionario EORTC QLQ-BR23 (breast)
12. Sopravvivenza libera da progressione nella linea terapeutica successiva (PFS2): la PFS2 è definita come il tempo dalla data della randomizzazione alla data della prima documentazione di PD sulla successiva terapia antitumorale sistemica secondo lo sperimentatore o il decesso per qualsiasi causa, a seconda di quale evento si verifichi per primo

E.5.2.1

Timepoint(s) of evaluation of this end point

1.From randomization date to date of death (up to approximately 6 years)
2, 3, 4, 5, 7. From randomization date to end of treatment (up to approximately 4 years)
6. From Baseline up to end of study (approximately 6.5 years)
8, 9, 10, 11. From Baseline to 90 days after end of treatment (up to approximately 4 years)
12.From randomization date to date of death (up to approximately 6.5 years)

1. Dalla data della randomizzazione alla data di decesso (fino a circa 6 anni)
2, 3, 4, 5, 7. Dalla data della randomizzazione alla fine del trattamento (fino a circa 4 anni)
6. Dal basale fino alla fine dello studio (circa 6,5 anni)
8, 9, 10, 11. Dal basale a 90 giorni dopo la fine del trattamento (fino a circa 4 anni).
12. Dalla data della randomizzazione alla data di decesso (fino a circa 6,5 anni)

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

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

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

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

Yes

E.8.1.7.1

Other trial design description

Disegno complesso: double-dummy

Complex design: double-dummy

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

112

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Brazil

Canada

Chile

China

Georgia

India

Japan

Korea, Republic of

Mexico

Russian Federation

Singapore

South Africa

Taiwan

Turkey

Ukraine

United States

Austria

Belgium

Bulgaria

Denmark

Estonia

Finland

France

Germany

Hungary

Italy

Netherlands

Poland

Portugal

Romania

Spain

United Kingdom

Czechia

Argentina

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:

800

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

533

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

386

F.4.2.2

In the whole clinical trial

1333

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)

none

nessuno

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

2020-11-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-09-16

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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