Clinical Trials Register

Summary
EudraCT Number:	2017-001994-18
Sponsor's Protocol Code Number:	SYD985.002
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-01-27
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

2017-001994-18

A.3

Full title of the trial

A multi-centre, open-label, randomized clinical trial comparing the efficacy and safety of the antibody-drug conjugate SYD985 to physician's choice in patients with HER2-positive unresectable locally advanced or metastatic breast cancer

Studio clinico, multicentrico, in aperto, randomizzato , teso a confrontare l'efficacia e la sicurezza del coniugato anticorpo-farmaco SYD985 rispetto a un trattamento a scelta del medico in pazienti con tumore mammario HER2-positivo localmente avanzato non resecabile o metastatico.

A.3.1

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

A study to compare the efficacy and safety of SYD985 to four standard available treatments in patients with HER2-positive unresectable locally advanced or metastatic breast cancer.

Studio per confrontare l'efficacia e la sicurezza di SYD985 rispetto a quattro trattamenti standard disponibili in pazienti con tumore mammario HER2-positivo localmente avanzato non resecabile o metastatico.

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

SYD985.002

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	SYNTHON BIOPHARMACEUTICAL BV
B.1.3.4	Country	Netherlands
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	Synthon Biopharmaceuticals BV
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Synthon Biopharmaceuticals BV
B.5.2	Functional name of contact point	Clinical Development
B.5.3	Address:
B.5.3.1	Street Address	Microweg 22
B.5.3.2	Town/ city	Nijmegen
B.5.3.3	Post code	6545 CM
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	0031243727700
B.5.5	Fax number	0031243727705
B.5.6	E-mail	Evelyn.vandenTweel@synthon.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	Trastuzumab vc-seco-DUBA
D.3.2	Product code	SYD985
D.3.4	Pharmaceutical form	Powder for solution for infusion
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	trastuzumab duocarmazine
D.3.9.1	CAS number	1642152-40-6
D.3.9.2	Current sponsor code	SYD985
D.3.10	Strength
D.3.10.1	Concentration unit	µg/kg microgram(s)/kilogram
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	900 to 1200
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)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	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	Yes
D.3.11.13.1	Other medicinal product type	Coniugato anticorpo-farmaco (ADC)
D.IMP: 2
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	TYVERB - 250 MG COMPRESSA RIVESTITA CON FILM - USO ORALE BLISTER (PA/ALU/PVC/ALU) 70 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	GLAXO GROUP LIMITED
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	lapatinib
D.3.2	Product code	NA
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	LAPATINIB
D.3.9.1	CAS number	231277-92-2
D.3.9.2	Current sponsor code	na
D.3.9.4	EV Substance Code	SUB25379
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	250
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	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	XELODA - 500 MG 120 COMPRESSE FILMRIVESTITE IN BLISTER USO ORALE
D.2.1.1.2	Name of the Marketing Authorisation holder	ROCHE REGISTRATION LIMITED
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	capecitabina
D.3.2	Product code	[NA]
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	CAPECITABINA
D.3.9.2	Current sponsor code	na
D.3.9.4	EV Substance Code	SUB12474MIG
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	500
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	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	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	HERCEPTIN - 150 MG POLVERE PER CONCENTRATO PER SOLUZIONE PER INFUSIONE ENDOVENOSA 1 FLACONCINO USO ENDOVENOSO
D.2.1.1.2	Name of the Marketing Authorisation holder	ROCHE REGISTRATION LIMITED
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	trastuzumab
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Powder for solution for infusion
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	TRASTUZUMAB
D.3.9.1	CAS number	180288-69-1
D.3.9.2	Current sponsor code	na
D.3.9.4	EV Substance Code	SUB12612MIG
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	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 5
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	HALAVEN - 0.44MG/ML - SOLUZIONE INIETTABILE - USO ENDOVENOSO - FLACONCINO(VETRO) 2ML 6 FLACONCINI
D.2.1.1.2	Name of the Marketing Authorisation holder	EISAI LTD
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	eribulina
D.3.2	Product code	[NA]
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	ERIBULINA
D.3.9.1	CAS number	253128-41-5
D.3.9.2	Current sponsor code	na
D.3.9.4	EV Substance Code	SUB31134
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0
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	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	NAVELBINE - 10 MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FLACONE 1 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	PIERRE FABRE PHARMA S.R.L.
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	vinorelbine
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
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	VINORELBINA
D.3.9.1	CAS number	71486-22-1
D.3.9.2	Current sponsor code	na
D.3.9.4	EV Substance Code	SUB00069MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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	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	XELODA - 150 MG 60 COMPRESSE FILMRIVESTITE IN BLISTER USO ORALE
D.2.1.1.2	Name of the Marketing Authorisation holder	ROCHE REGISTRATION LIMITED
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	capecitabina
D.3.2	Product code	NA
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	CAPECITABINA
D.3.9.2	Current sponsor code	na
D.3.9.4	EV Substance Code	SUB12474MIG
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	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	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	HERCEPTIN - 600 MG/5 ML SOLUZIONE INIETTABILE - USO SOTTOCUTANEO - FLACONCINO (VETRO) DA 6 ML - 1 FLACONCINO
D.2.1.1.2	Name of the Marketing Authorisation holder	ROCHE REGISTRATION LIMITED
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	trastuzumab
D.3.2	Product code	[NA]
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	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TRASTUZUMAB
D.3.9.1	CAS number	180288-69-1
D.3.9.2	Current sponsor code	na
D.3.9.4	EV Substance Code	SUB12612MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	120
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

breast tumours

tumori al seno

E.1.1.1

Medical condition in easily understood language

breast tumours

tumori al seno

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	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10006317
E.1.2	Term	Breast tumour malignant
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to demonstrate that SYD985 is superior to physician's choice in prolonging PFS on the basis of the blinded independent central review of tumour assessment.

L'obiettivo primario di questo studio ¿ dimostrare che SYD985 ¿ superiore alla scelta del medico nel prolungare la sopravvivenza libera da progressione (Progression-Free Survival, PFS) sulla base dell'esame del laboratorio centrale indipendente in cieco della valutazione del tumore.

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are to compare the two treatment groups with respect to:
¿Overall survival (OS);
¿Objective response rate (ORR) on the basis of the blinded independent central review;
¿Investigator assessed PFS;
¿Patient reported outcomes for health related quality of life;
¿Safety and tolerability.

Gli obiettivi secondari di questo studio sono confrontare i due gruppi di trattamento rispetto a:
¿ Sopravvivenza globale (OS);
¿ Tasso di risposta obiettiva (ORR) sulla base dell'esame centrale indipendente in cieco;
¿ PFS secondo la valutazione dello sperimentatore;
¿ esiti riportati dal paziente per la qualit¿ della vita in relazione alla salute;
¿ sicurezza e tollerabilit¿.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Female patients, age = 18 years old at the time of signing informed consent;
2. Patients with histologically-confirmed, unresectable locally advanced or metastatic breast cancer;
3. Patients should have had either progression during or after at least two HER2-targeting treatment regimens for locally advanced or metastatic disease or progression during or after (ado-)trastuzumab emtansine treatment for locally advanced or metastatic disease;
4. HER2-positive tumour status according to the ASCO-CAP guidelines (defined as a 3+ score on immunohistochemistry (IHC) and/or positive by in situ hybridization (ISH)) confirmed by the central laboratory;
5. Patients must have measurable or non-measurable disease that is evaluable per Response Evaluation Criteria for Solid Tumours (RECIST version 1.1). Patients with bone-only sclerotic disease without a lytic component are not eligible;
6. Eastern Cooperative Oncology Group (ECOG) performance status = 2;
7. Estimated life expectancy > 12 weeks at randomization;
8. Adequate organ function, evidenced by the following (local) laboratory results:
–Absolute neutrophil count = 1.5 x 109/L;
–Platelet count = 100 x 109/L;
–Hemoglobin = 9.0 g/dL;
–Total bilirubin = 1.5 x the upper limit of normal (ULN);
–Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
= 3.0 x ULN (or = 5.0 x ULN in the presence of liver metastases);
–Serum creatinine = 1.5 x ULN;
9. For women of childbearing potential two methods of effective contraception must be used during the study and up to 6 months after last study treatment. This is not required in case the patient or sole partner is surgically sterilized or in case the patient truly abstains from sexual activity.

1. Pazienti donne, età = 18 anni al momento della firma del consenso informato.
2. Pazienti con tumore mammario localmente avanzato non resecabile o metastatico, confermato istologicamente.
3. Le pazienti devono aver presentato progressione durante o dopo almeno due regimi di trattamento anti-HER2 per malattia localmente avanzata o metastatica o progressione durante o dopo il trattamento con (ado-) trastuzumab emtansine per malattia localmente avanzata o metastatica.
4. Lo stato del tumore HER2-positivo secondo le lineeguida ASCO_CAP (definito con un punteggio di immunoistochimica (IHC) pari a 3+ e/o positivo mediante ibridazione in situ (In Situ Hybridization, ISH)) confermato dal laboratorio centrale.
5. Le pazienti devono presentare una malattia misurabile o non misurabile che sia valutabile secondo i criteri di valutazione delle risposte per tumori solidi (Response Evaluation Criteria for Solid Tumours, RECIST versione 1.1). Le pazienti con malattia sclerotica solo ossea senza componente litica non sono idonee.
6. Stato di validità ECOG (Eastern Cooperative Oncology Group) = 2.
7. Aspettativa di vita stimata > 12 settimane al momento della randomizzazione.
8. Funzionalità organica adeguata, evidenziata dai seguenti risultati del laboratorio locale:
– Conta assoluta dei neutrofili = 1,5 x 109/l
– Conta piastrinica = 100 x 109/l
– Emoglobina = 9,0 g/dl
– Bilirubina totale =1,5 x il limite superiore normale (ULN)
– Aspartato aminotransferasi (AST) e alanina aminotransferasi (ALT) = 3,0 x ULN (o = 5,0 x ULN in presenza di metastasi epatiche)
– Creatinina sierica =1,5 volte ULN
9. Le donne in grado di procreare devono utilizzare due metodi di contraccezione efficace durante lo studio e fino a sei mesi dopo l'ultimo trattamento dello studio. Ciò non è necessario nel caso in cui la paziente, o il partner, sia sterilizzata/o chirurgicamente o si astenga veramente dall'attività sessuale.

E.4

Principal exclusion criteria

1. Having been treated with:
a. SYD985 at any time;
b. Anthracycline treatment within 12 weeks prior to randomization;
c. Other anticancer therapy including chemotherapy, immunotherapy, or investigational agents within 4 weeks prior to randomization;
d. Radiotherapy within 2 weeks prior to randomization;
e. Hormone therapy within 1 week prior to randomization;
The patient must have sufficiently recovered from any treatment-related toxicities to NCI CTCAE Grade = 1 (except for toxicities not considered a safety risk for the patient at the investigator's discretion);
2. History of infusion-related reactions and/or hypersensitivity to trastuzumab, (ado-)trastuzumab emtansine or excipients of the study drug which led to permanent discontinuation of the treatment;
3. History of keratitis;
4. Severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary, or metabolic disease) at screening;
5. Left ventricular ejection fraction (LVEF) < 50% as assessed by either echocardiography or multigated acquisition (MUGA) scan at screening, or a history of clinically significant decrease in LVEF during previous treatment with trastuzumab or (ado-)trastuzumab emtansine leading to permanent discontinuation of treatment;
6. Cardiac troponin value above the ULN (local laboratory) at screening;
7. History (within 6 months prior to randomization) of clinically significant cardiovascular disease such as unstable angina, congestive heart failure (CHF), myocardial infarction, uncontrolled hypertension, or cardiac arrhythmia requiring medication;
8. Untreated brain metastases, symptomatic brain metastases, brain metastases requiring steroids to manage symptoms, or treatment for brain metastases within 8 weeks prior to randomization. Patients with prior treatment of brain metastasis must have evidence of disease stability on baseline brain imaging as compared to historical brain
imaging;
9. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic neumonitis, or evidence of active pneumonitis on screening chest CT scan
10. Known active Hepatitis B or C infection;
11. Major surgery within 4 weeks prior to randomization;
12. Pregnancy or lactation;
13. Other condition, which in the opinion of the investigator, would compromise the safety of the patient or the patient's ability to complete the study.

1. Precedente trattamento con:
a. SYD985 in qualsiasi momento.
b. Trattamento con antraciclina nelle 12 settimane precedenti la randomizzazione.
c. Altre terapie antitumorali comprese chemioterapia, immunoterapia o agenti sperimentali nelle 4 settimane precedenti la randomizzazione.
d. Radioterapia nelle 2 settimane precedenti la randomizzazione.
e. Ormonoterapia nella settimana precedente la randomizzazione.
La paziente deve essersi sufficientemente ripresa da tossicità correlata al trattamento raggiungendo il grado =1 secondo i criteri NCI CTCAE (ad eccezione delle tossicità non considerate un rischio per la sicurezza della paziente a discrezione dello sperimentatore).
2. Anamnesi di reazioni correlate all'infusione e/o ipersensibilità a trastuzumab, (ado-)trastuzumab emtansine o agli eccipienti del farmaco dello studio che hanno portato a interruzione permanente del trattamento.
3. Anamnesi di cheratite.
4. Malattia sistemica grave non controllata (ad es. malattia cardiovascolare, polmonare o metabolica clinicamente significativa) allo screening.
5. Frazione di eiezione del ventricolo sinistro (Left Ventricular Ejection Fraction, LVEF) <50% valutata mediante ecocardiografia o arteriografia a porte multiple (MUGA) allo screening, o anamnesi di diminuzione clinicamente significativa di LVEF durante il precedente trattamento con trastuzumab o (ado-)trastuzumab emtansine con conseguente interruzione permanente del trattamento.
6. Valore della troponina cardiaca superiore a ULN (laboratorio locale) allo screening.
7. Anamnesi (nei 6 mesi precedenti la randomizzazione) di malattia cardiovascolare clinicamente significativa quale angina instabile, insufficienza cardiaca congestizia (CHF), infarto miocardico, ipertensione non controllata o aritmia cardiaca che richieda farmaci.
8. Metastasi cerebrali non trattate, metastasi cerebrali sintomatiche, metastasi cerebrali che richiedono steroidi per gestire i sintomi o trattamento per metastasi cerebrali nelle 8 settimane prima della randomizzazione. Le pazienti sottoposte a precedente trattamento di metastasi cerebrali devono evidenziare stabilità della malattia su immagini radiologiche del cervello al basale rispetto a precedenti immagini radiologiche del cervello.
9. Anamnesi di fibrosi idiopatica polmonare, polmonite organizzata (es. bronchiolite obliterante), polmonite farmaco-indotta o polmonite idiopatica, o evidenza di polmonite attiva durante la TAC toracica dello screening
10. Infezione nota da epatite B o C attiva.
11. Intervento di chirurgia maggiore nelle 4 settimane prima della randomizzazione.
12. Gravidanza o allattamento.
13. Altra condizione, che a giudizio dello sperimentatore comprometterebbe la sicurezza della paziente o la capacità della paziente di completare lo studio.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is PFS based on blinded independent central review (ICR) of tumour assessment according to RECIST 1.1.

L'endopoint primario di efficacia è la Sopravvivenza Libera da Progressione di Malattia (Progression-Free Survival, PFS) basata sulla revisione centrale indipendente in cieco (ICR) della valutazione del tumore secondo il RECIST 1.1.

E.5.1.1

Timepoint(s) of evaluation of this end point

PFS is defined as the time from the date of randomization to the date of first documented ICR-assessed disease progression according to RECIST 1.1 or death due to any cause (whichever occurs earlier).

La PFS è definite come il tempo dalla data di randomizzazione alla data della prima progressione di malattia documentata dall'ICR secondo il RECIST 1.1 o il decesso dovuto a qualsiasi causa (l'evento che si manifesta per primo).

E.5.2

Secondary end point(s)

The secondary efficacy endpoints are:
¿ Overall Survival;
¿ Objective Response Rate on the basis of the blinded independent
central review;
¿ Investigator assessed PFS;
¿ Patient reported outcomes for health related quality of life;

Enpoint secondari
¿ Sopravvivenza globale (OS)
¿ Tasso di risposta obiettiva (ORR) sulla base dell'esame di un laboratorio centrale indipendente in cieco
¿ PFS secondo la valutazione dello sperimentatore;
¿ Esiti riportati dal paziente per la qualit¿ della vita in relazione alla salute

E.5.2.1

Timepoint(s) of evaluation of this end point

As per trial flow chart documented in the protocol

Come descritto nella flow chart dello studio riportata nel protocollo

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

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

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

Canada

Singapore

United States

Belgium

Denmark

France

Italy

Netherlands

Spain

Sweden

United Kingdom

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:

322

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

101

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

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

324

F.4.2.2

In the whole clinical trial

423

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. Trial participation will be until disease progression or unacceptable toxicity.

Nessuno. La partecipazione allo studio continuer¿ fino a progressione di malattia o tossicit¿ inaccettabile

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

2018-01-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-11-09

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

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