Clinical Trials Register

Summary
EudraCT Number:	2016-003881-14
Sponsor's Protocol Code Number:	CA209-901
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:	2021-06-17
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2016-003881-14

A.3

Full title of the trial

A Phase 3, Open-label, Randomized Study of Nivolumab Combined with
Ipilimumab, or with Standard of Care Chemotherapy, versus Standard of
Care Chemotherapy in Participants with Previously Untreated Unresectable
or Metastatic Urothelial Cancer

Studio in fase 3, in aperto, randomizzato di Nivolumab combinato con Ipilimumab o con chemioterapia standard di cura, rispetto a chemioterapia standard di cura nei soggetti con carcinoma uroteliale precedentement non trattato, non resecabile o metastatico

A.3.1

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

A study of Nivolumab combined with Ipilimumab or Standard of Care chemotherapy, versus standard of care chemotherapy in patients with previously untreated unresectable or metastatic urothelial cancer.

Studio di nivolumab combinato ad ipilimumab o con chemioterapia standard di cura verso chemioterapia standard di cura in soggetti affetti da carcinoma uroteliale precedentemente non trattato, non reseabile o metastatico.

A.3.2

Name or abbreviated title of the trial where available

CheckMate 901: CHECKpoint pathway and nivoluMAb clinical Trial

CA209-901 (CheckMate 901)

A.4.1

Sponsor's protocol code number

CA209-901

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03036098

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1187-9637

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	BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
B.1.3.4	Country	Belgium
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	Bristol-Myers Squibb International Corporation
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bristol-Myers Squibb International Corporation
B.5.2	Functional name of contact point	GCT-SU
B.5.3	Address:
B.5.3.1	Street Address	Parc de l'Alliance - Avenue de Finlande, 4
B.5.3.2	Town/ city	Braine-l'Alleud
B.5.3.3	Post code	1420
B.5.3.4	Country	Belgium
B.5.4	Telephone number	000
B.5.5	Fax number	000
B.5.6	E-mail	clinical.trials@bms.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	Yes
D.2.1.1.1	Trade name	Opdivo (100 mg/10 ml)
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb Pharma 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.3.4	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	NIVOLUMAB
D.3.9.1	CAS number	946414-94-4
D.3.9.2	Current sponsor code	BMS-936558
D.3.9.3	Other descriptive name	MDX1106, ONO-4538
D.3.9.4	EV Substance Code	SUB32944
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	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: 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	Yervoy (200mg/40ml)
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb Pharma 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.3.4	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	ipilimumab
D.3.9.1	CAS number	477202-00-9
D.3.9.2	Current sponsor code	BMS-734016
D.3.9.3	Other descriptive name	MDX010/MDX-CTLA-4
D.3.9.4	EV Substance Code	SUB22577
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	5
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: 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	PARAPLATIN 450 mg/45 ml solution for infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb, S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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.3.4	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	CARBOPLATINO
D.3.9.2	Current sponsor code	N/A
D.3.9.3	Other descriptive name	CARBOPLATIN
D.3.9.4	EV Substance Code	SUB06614MIG
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: 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	Gemcitabine 38 mg/ml Concentrate for Solution for Infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Hospira UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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.3.4	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	GEMCITABINA CLORIDRATO
D.3.9.2	Current sponsor code	N/A
D.3.9.3	Other descriptive name	GEMCITABINE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB02324MIG
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	38
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	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	Cisplatin NeoCorp¿ 1 mg/ml ¿ Concentrate for solution for infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Hexal AG
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.3.4	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	CISPLATINO
D.3.9.2	Current sponsor code	Not available
D.3.9.3	Other descriptive name	CISPLATIN
D.3.9.4	EV Substance Code	SUB07483MIG
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	1
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	Cisplatin-Ebewe, 1 mg/ml, concentrate for solution for infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	EBEWE Pharma Ges.m.b.H. Nfg. KG
D.2.1.2	Country which granted the Marketing Authorisation	Poland
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.3.4	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	CISPLATINO
D.3.9.2	Current sponsor code	Not applicable
D.3.9.3	Other descriptive name	CISPLATIN
D.3.9.4	EV Substance Code	SUB07483MIG
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	1
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	Gemcitabine 1 g Powder for Solution for Infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Accord Healthcare Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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.3.4	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	GEMCITABINA CLORIDRATO
D.3.9.1	CAS number	00-00-0
D.3.9.2	Current sponsor code	000
D.3.9.3	Other descriptive name	GEMCITABINE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB02324MIG
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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	Cisplatin TEVA, 1mg/ml concentrate for solution for infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	TEVA 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.3.4	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.3.11 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	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	No
D.2.1.1.1	Trade name	Carboplatin-Actavis 10mg/ml concentrate for solution for infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Actavis Group PTC ehf.
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	NA
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	CARBOPLATIN
D.3.9.2	Current sponsor code	NA
D.3.9.4	EV Substance Code	SUB06614MIG
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.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

Untreated Unresectable or Metastatic Urothelial Cancer

carcinoma uroteliale precedentemente non trattato, non resecabile o metastatico

E.1.1.1

Medical condition in easily understood language

Untreated Inoperable or Metastatic Urothelial Cancer

carcinoma uroteliale non trattato e inoperabile

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	LLT
E.1.2	Classification code	10064467
E.1.2	Term	Urothelial carcinoma
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

To compare Overall Survival (OS), and Progression Free Survival (PFS) of nivolumab combined with ipilimumab versus standard of care (SOC) chemotherapy in cisplatin-ineligible participants with previously untreated, unresectable or metastatic urothelial carcinoma (UC).

Confrontare La sopravvivenza complessiva (OS) e la sopravvivenza libera da progressione (PFS) , di nivolumab in combinazione con ipilimumab rispetto alla chemioterapia standard di cura (standard of care, SOC) in partecipanti non eleggibili a ricevere cisplatino, affetti da carcinoma uroteliale (UC) non pretrattato, non resecabile o metastatico

E.2.2

Secondary objectives of the trial

To compare OS and PFS of nivolumab combined with ipilimumab versus SOC chemotherapy in all randomized participants with previously untreated, unresectable or metastatic UC. To evaluate changes from baseline in Health-Related QOL (HRQoL) of nivolumab combined with ipilimumab versus SOC chemotherapy in all randomized participants with previously untreated, unresectable or metastatic UC. To evaluate whether PD-L1 expression is a predictive biomarker of efficacy (PFS and OS) of nivolumab combined with ipilimumab as first-line therapy in participants with previously untreated, unresectable or metastatic UC.

Confrontare OS e PFS di nivolumab in combinazione con ipilimumab rispetto alla chemioterapia SOC in tutti i partecipanti randomizzati affetti da UC non pretrattato, non resecabile o metastatico. Valutare le variazioni dal basale nel (quality of life, QOL ) correlata alla salute (HRQoL) di nivolumab in combinazione con ipilimumab rispetto alla chemioterapia SOC in tutti i partecipanti randomizzati affetti da UC non pretrattato, non resecabile o metastatico. Valutare se l¿espressione di PD-L1 sia un biomarcatore predittivo dell¿ efficacia (PSF e OS) di nivolumab combinato con ipilimumab come terapia di prima linea nei parteciapnti affetti da UC non pretrattato, non resecabile o metastatico

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

Pharmacogenetics
Version: Revised Protocol Number: 02
Date: 21/04/2017
Title: A Phase 3, Open-label, Randomized Study of Nivolumab Combined with Ipilimumab, or with Standard of Care Chemotherapy, versus Standard of Care Chemotherapy in Participants with Previously Untreated Unresectable or Metastatic Urothelial Cancer.
Objectives: This protocol will include both sample collection and residual sample
storage for additional research (AR).
For more details please refer to section 9.8.1 of the protocol.
Main objective of the substudy as per revised protocol 02 dated 21-Apr-
2017 (A Phase 3, Open-label, Randomized Study of Nivolumab Combined
with Ipilimumab, or with Standard of Care Chemotherapy, versus
Standard of Care Chemotherapy in Participants with Previously
Untreated Unresectable or Metastatic Urothelial Cancer): To compare
PFS of nivolumab combined with SOC chemotherapy versus SOC
chemotherapy in cisplatin-eligible participants with previously
untreated, unresectable or metastatic urothelial carcinoma (UC)
Secondary Objectives of the substudy as per revised protocol 02 dated
XML File Identifier: O9+soSeoLQPKS67UvV2dwGtVen4=
Page 39/56
21-Apr-2017:
-To compare OS of nivolumab combined with SOC chemotherapy versus
SOC chemotherapy in cisplatin-eligible participants with previously
untreated, unresectable or metastatic UC
-To evaluate changes from baseline in Health-Related QOL (HRQoL) of
nivolumab combined with SOC chemotherapy versus SOC chemotherapy
in cisplatin-eligible participants with previously untreated, unresectable
or metastatic UC
-To evaluate whether PD-L1 expression is a predictive biomarker of
efficacy (PFS and OS) of nivolumab combined with SOC chemotherapy as
first-line therapy in participants with previously untreated, unresectable
or metastatic UC

Pharmacogenomics
Version: Revised Protocol Number: 01
Date: 19/12/2016
Title: A Phase 3, Open-label, Randomized Study of Nivolumab Combined with Ipilimumab versus Standard of Care Chemotherapy in Participants with Previously Untreated Unresectable or Metastatic Urothelial Cancer
Objectives: This protocol will include both sample collection and residual sample storage for additional research (AR).
Additional research is optional for all study articipants, except where retention and/or collection is prohibited by local laws or regulations,
ethics committees, or institutional requirements.
This collection for additional research is intended to expand the translational R&D capability at Bristol-Myers Squibb, and will support as yet undefined research aims that will advance our understanding of
disease and options for treatment. It may also be used to support health authority requests for analysis, and advancement of pharmacodiagnostic
development to better target drugs to the right patients. This may also include genetic/genomic exploration aimed at exploring disease pathways, progression and response to treatment etc.
Prospective samples of tumor tissue (optional), whole blood, serum samples, PMBC, and MDSCs will be collected at selected time points.
Residual tumor tissue from baseline tumor tissue collections will also be retained for additional research purposes.
For more details please refer to section 9.8.1 of the protocol.

Farmacogenetica
Versione: Revised Protocol Number: 02
Data: 21/04/2017
Titolo: Studio in fase 3, in aperto, randomizzato di Nivolumab combinato con Ipilimumab o con chemioterapia standard di cura, rispetto a chemioterapia standard di cura nei soggetti con carcinoma uroteliale precedentement non trattato, non resecabile o metastatico
Obiettivi: Il protocollo includer¿ raccolta e stoccaggio dei campioni residui per ulteriori ricerche (AR). Per maggiori dettagli, fare riferimento alla sezione 9.8.1 del protocollo.
Obiettivo principale del sottostudio come da rev. prot. 02 del 21 aprile 2017 (Studio in fase 3, in aperto, randomizzato di Nivolumab combinato con Ipilimumab o con chemioterapia standard di cura, rispetto a chemioterapia standard di cura nei soggetti con carcinoma uroteliale precedentement non trattato, non resecabile o metastatico): confrontare PFS di nivolumab combinato con la chemioterapia SOC nei soggetti eleggibili al cisplatino con carcinoma uroteliale precedentement non trattato, non resecabile o metastatico. Obiettivi secondari del sottostudio come da rev. prot. 2.0 datato 21 Aprile 2017:
Valutare l'OS di nivolumab in combinazione con la chemioterapia SOC rispetto alla chemioterapia SOC nei partecipanti eleggibili al cisplatino con con UC precedentement non trattato, non resecabile o metastatico. Valutare le variazioni dal basale nel QOL correlata alla salute (HRQoL) di nivolumab in combinazione con chemioterapia SOC rispetto alla chemioterapia SOC in tutti i partecipanti elegibbili al cisplatino affetti da UC non pretrattato, non resecabile o metastatico.
Valutare se l¿espressione di PD-L1 sia un biomarcatore predittivo dell¿ efficacia (PSF e OS) di nivolumab combinato con chemioterapia SOC come terapia di prima linea nei partecipanti affetti da UC non pretrattato, non resecabile o metastatico

Farmacogenomica
Versione: Revised Protocol Number: 01
Data: 19/12/2016
Titolo: Studio di fase III, in aperto, randomizzato, sull¿uso di Nivolumab combinato con Ipilimumab verso chemioterapia standard di cura in soggetti con carcinoma uroteliale precedentemente non trattato, non resecabile o metastatico
Obiettivi: Questo protocollo includer¿ sia la raccolta di nuovi campioni che l¿archiviazione di campioni residui per ricerca addizionale (AR). La ricerca addizionale ¿ facoltativa per tutti i partecipanti allo studio, salvo dove la ritenzione e/o la raccolta sono vietati da leggi o regolamenti locali, da Comitati etici o requisiti istituzionali.
Questa raccolta per ulteriori ricerche ha lo scopo di espandere la capacit¿ di Ricerca e Sviluppo (R&D) di Bristol-Myers Squibb e supporter¿ non ancora definiti scopi di ricerca che faranno avanzare la comprensione della malattie e delle opzioni per il trattamento. Pu¿ anche essere utilizzata per sostenere richieste delle autorit¿ sanitarie per l'analisi e l'avanzamento dello sviluppo farmacodiagnostico per meglio mirare i farmaci ai pazienti. Questo pu¿ anche includere l'esplorazione genetica/genomica finalizzata all'esplorazione del decorso della malattia, la progressione e la risposta al trattamento, ecc.
Campioni di tessuto tumorale prospettici (opzionali), sangue intero, campioni di siero, PMBC e MDSC saranno raccolti a definite tempistiche.
Anche il tessuto tumorale residuo raccolto al baseline sar¿ conservato per ulteriori ricerche.
Per maggiori dettagli, fare riferimento alla sezione 9.8.1 del protocollo.

E.3

Principal inclusion criteria

- Metastatic or inoperable urothelial cancer
- Must have at least 1 lesion with measurable disease
- Must have full activity or, if limited, must be able to walk and carry out
light activities such as light house work or office work
- No prior systemic chemotherapy treatment in the metastatic setting

- Carcinoma uroteliale metastatico o inoperabile
- Deve avere almeno 1 lesione misurabile di malattia
- Deve avere piena attività o, se limitata, deve poter camminare ed eseguire attività leggere come il lavoro a casa leggera o in ufficio
- Nessun precedente trattamento chemioterapico sistemico in ambito metastatico

E.4

Principal exclusion criteria

- Patients with disease that is suitable for local therapy administered
with curative intent
- Patients with active brain metastases or leptomeningeal metastases
- Patients with active, known or suspected autoimmune disease
- Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.

- Pazienti con malattia idonei alla terapia locale somministrata con intento curativo
- Pazienti con metastasi cerebrali attive o metastasi leptomeningee
- Pazienti con malattia autoimmune attiva, conosciuta o sospetta
- trattamento precedente con un anticorpo anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 o anti-CTLA-4 o qualsiasi altro anticorpo o farmaco specificamente destinato alla co-stimolazione delle cellule T o di checkpoint cellulari.

E.5 End points

E.5.1

Primary end point(s)

Main study: Co-primary endpoint of Overall Survival (OS), and Progression Free Survival (PFS) by blinded independent central review (BICR) (using RECIST 1.1), in cisplatin-ineligible participants with previously untreated, unresectable or metastatic UC.
Substudy (revised protocol 02 dated 21Apr-2017): PFS by BICR (using RECIST 1.1) in cisplatin-eligible participants with previously untreated, unresectable or metastatic UC.

Studio principale: Endpoint co-primario di OS e, PFS, valutate mediante revisione centrale indipendente in cieco (blinded independent central review, BICR) (utilizzando i criteri RECIST 1.1), in partecipanti non eleggibili a ricevere cisplatino, affetti da UC non pretrattato, non resecabile o metastatico.
Sottostudio (revised protocol 02 datato 21 Aprile 2017): PFS valutato mediante BICR (utilizzando i criteri RECIST 1.1) in tutti i partecipanti affetti da UC precedentemente non pretrtattato, non resecabile o metastatico, elegibbili al cisplatino

E.5.1.1

Timepoint(s) of evaluation of this end point

Up to 42 months from the randomization of the first participant in main study.
Substudy: Up to 43 months form the randomization of the first participant in the sub study.

fino a 42 mesi dalla randomizzazione del primo partecipante nello studio principale
Sottostudio: Fino a 43 mesi dalla randomizzazione del primo partecipante nel sottostudio.

E.5.2

Secondary end point(s)

Secondary Endpoint Main Study: 1- OS, and PFS by BICR (using RECIST 1.1) in all randomized participants with previously untreated, unresectable or metastatic UC.
2- European Organization for Research and Treatment of Care (EORTC) QLQ-C30 Global Health Status score
3- PFS by BICR (using RECIST 1.1) and OS by PD-L1 expression at = 1% expression by immunohistochemistry (IHC)
Substudy (revised protocol 02 dated 21Apr2017):
1- OS in cisplatin-eligible participants with previously untreated, unresectable or metastatic UC
2- European Organization for Research and Treatment of Care (EORTC) QLQ-C30 Global Health Status score
3- PFS by BICR (using RECIST 1.1) and OS by PD-L1 expression at = 1% expression by immunohistochemistry (IHC)

Studio Principale:
1- OS e PFS valutate mediante BICR (utilizzando i criteri RECIST 1.1) in tutti i partecipanti randomizzati affetti da UC precedentemente non pretrattato, non resecabile o metastatico
2- Punteggio del questionario European Organization for Research and Treatment Care (EORTC) QLQ-C30 per la valutazione dello stato di salute generale
3 - PFS valutato mediante BICR (utilizzando i criteri di RECIST 1.1) e OS valutato mediante l¿espressione di PD-L1 > 1% tramite immunoistochimica (IHC)
Sottostudio: (revised protocol 02 datato 21-Aprile-2017)
1- OS in tutti i partecipanti elegibbili al cisplatino affetti da UC precedentemente non pretrattato, non resecabile o metastatico
2- Punteggio del questionario European Organization for Research and Treatment Care (EORTC) QLQ-C30 per la valutazione dello stato di salute generale
3- PFS valutato mediante BICR (utilizzando i criteri di RECIST 1.1) e OS valutato mediante l¿espressione di PD-L1 > 1% tramite immunoistochimica (IHC)

E.5.2.1

Timepoint(s) of evaluation of this end point

Main study (from the first participant¿s randomization date in main study)
1-up to 42 months
2-up to 28 months
3-up to 42 months
Substudy (from the randomization of the first participant in the sub study)
1-up to 43 months
2-up to 28 months
3-up to 43 months

Studio Principale: (dalla data del primo partecipante randomizzato nello studio principale)
1- fino a 42 mesi
2- fino a 28 mesi
3- fino a 42 mesi
Sottostudio (dalla randomizzazione del primo partecipante nel sottostudio)
1-fino a 43 mesi
2-fino a 28 mesi
3-fino a 43 mesi

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

Yes

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

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

Australia

Brazil

Canada

Chile

China

Japan

Korea, Republic of

Peru

Taiwan

United States

Finland

France

Germany

Greece

Italy

Netherlands

Norway

Spain

Sweden

Switzerland

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

End of trial is defined as last participant last visit on the Schedule of Activities.

La fine dello studio clinico ¿ definita come l¿ultima visita dell¿ultimo partecipante.

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:

204

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

1156

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

190

F.4.2.2

In the whole clinical trial

1360

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

At the conclusion of the study, participants who continue to
demonstrate clinical benefit will be eligible to receive BMS supplied
study treatment. Study treatment will be provided via an extension of
the study, a rollover study requiring approval by responsible health
authority and ethics committee or through another mechanism at the discretion of BMS. See section 7.8 of the protocol

Alla conclusione dello studio, i partecipanti che continuano a dimostrare il beneficio clinico saranno elegibili a ricevere il trattamento in studio fornito da BMS. Il trattamento in studio sar¿ fornito tramite un'estensione dello studio, uno studio di rollover che richiede l'approvazione da parte dell'autorit¿ sanitarie responsabili e dei comitati etici o attraverso un altro meccanismo a discrezione del BMS. Vedere la sezione 7.8 del protocollo

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

2017-09-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-07-20

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

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Orphan Designation Number:
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