Clinical Trials Register

Summary
EudraCT Number:	2015-003656-40
Sponsor's Protocol Code Number:	PCYC-1128-CA
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2015-12-10
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

Spain - AEMPS

A.2

EudraCT number

2015-003656-40

A.3

Full title of the trial

A Phase 1b/2 Study of Ibrutinib Combination Therapy in Selected Advanced Gastrointestinal And Genitourinary Tumors

Estudio en fase 1b/2 del tratamiento combinado con Ibrutinib en tumores gastrointestinales y genitourinarios avanzados seleccionados

A.3.1

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

A Phase 1b/2 Study of Ibrutinib Combination Therapy in Selected Advanced Gastrointestinal And Genitourinary Tumors

Estudio en fase 1b/2 del tratamiento combinado con Ibrutinib en tumores gastrointestinales y genitourinarios avanzados seleccionados

A.3.2

Name or abbreviated title of the trial where available

PCYC-1128-CA

A.4.1

Sponsor's protocol code number

PCYC-1128-CA

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	Pharmacyclics LLC
B.1.3.4	Country	United States
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	Pharmacyclics LLC
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Pharmacyclics LLC
B.5.2	Functional name of contact point	Clinical Trial Manager
B.5.3	Address:
B.5.3.1	Street Address	995 East Arques Avenue
B.5.3.2	Town/ city	Sunnyvale, CA
B.5.3.3	Post code	94085
B.5.3.4	Country	United States
B.5.4	Telephone number	1425968 2664
B.5.5	Fax number	1408215 3738
B.5.6	E-mail	jherendeen@pcyc.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	Ibrutinib (PCI-32765)
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
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.3.1	Product name	Ibrutinib
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	IBRUTINIB
D.3.9.1	CAS number	936563-96-1
D.3.9.2	Current sponsor code	PCI-32765
D.3.9.3	Other descriptive name	IBRUTINIB
D.3.9.4	EV Substance Code	SUB120863
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	140
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	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	Everolimus
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
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.3.1	Product name	Everolimus
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	EVEROLIMUS
D.3.9.1	CAS number	159351-69-6
D.3.9.2	Current sponsor code	RAD001
D.3.9.3	Other descriptive name	EVEROLIMUS
D.3.9.4	EV Substance Code	SUB02065MIG
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	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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	Docetaxel
D.2.1.1.2	Name of the Marketing Authorisation holder	Aventis Pharma, Dagenham
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.3.1	Product name	Docetaxel
D.3.4	Pharmaceutical form	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	DOCETAXEL
D.3.9.1	CAS number	114977-2
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	DOCETAXEL
D.3.9.4	EV Substance Code	SUB12492MIG
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	20 mg/0.5 mL
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	Paclitaxel
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe Limited
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 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	PACLITAXEL
D.3.9.1	CAS number	33069-62-4
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	PACLITAXEL
D.3.9.4	EV Substance Code	SUB09583MIG
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	30
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	Docetaxel
D.2.1.1.2	Name of the Marketing Authorisation holder	Aventis Pharma, Dagenham
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.3.1	Product name	Docetaxel
D.3.4	Pharmaceutical form	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	DOCETAXEL
D.3.9.1	CAS number	114977-2
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	DOCETAXEL
D.3.9.4	EV Substance Code	SUB12492MIG
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	80mg/2mL
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	Paclitaxel
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe Limited
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 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	PACLITAXEL
D.3.9.1	CAS number	33069-62-4
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	PACLITAXEL
D.3.9.4	EV Substance Code	SUB09583MIG
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	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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	Paclitaxel
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe Limited
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 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	PACLITAXEL
D.3.9.1	CAS number	33069-62-4
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	PACLITAXEL
D.3.9.4	EV Substance Code	SUB09583MIG
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	300
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	Cetuximab
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck KGaA
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	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	CETUXIMAB
D.3.9.1	CAS number	205923-56-4
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	Cetuximab
D.3.9.4	EV Substance Code	SUB01178MIG
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	2
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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

Metastatic renal cell carcinoma (RCC), advanced urothelial carcinoma, advanced gastric (including gastro-esophageal [GEJ]) adenocarcinoma, and metastatic colorectal adenocarcinoma (CRC)

Carcinoma de células renales (CCR) metastásico previamente tratado, carcinoma urotelial avanzado, adenocarcinoma gástrico avanzado (incluyendo gastroesofágico [UGE]) y adenocarcinoma colorrectal (ACR) metastásico

E.1.1.1

Medical condition in easily understood language

kidney cancer, bladder cancer, stomach-throat cancer, colon cancer

Cáncer de riñón, cáncer de vejiga, cáncer de estómago-gestroesofágico, cáncer de colon

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	18.1
E.1.2	Level	PT
E.1.2	Classification code	10052360
E.1.2	Term	Colorectal adenocarcinoma
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	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10064467
E.1.2	Term	Urothelial carcinoma
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	18.1
E.1.2	Level	PT
E.1.2	Classification code	10050513
E.1.2	Term	Metastatic renal cell carcinoma
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	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10071114
E.1.2	Term	Metastatic gastric adenocarcinoma
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

Phase 1b:
Primary Objective:
To determine the recommended Phase 2 dose (RP2D) of ibrutinib in combination with everolimus in RCC, paclitaxel in urothelial carcinoma, docetaxel in gastric adenocarcinoma and cetuximab in CRC.

Phase 2:
Primary Objectives:
To assess progression-free survival (PFS) of ibrutinib combination therapy in RCC and urothelial carcinoma
To assess the ORR of ibrutinib combination therapy in gastric adenocarcinoma and CRC

Fase 1b:
Objetivo principal:
Determinar la dosis recomendada para la Fase 2 (DRF2) de ibrutinib en combinación con everolimus para CCR, de paclitaxel para carcinoma urotelial, de docetaxel para adenocarcinoma gástrico y de cetuximab para ACR.

Fase 2:
Objetivos principales:
Evaluar la supervivencia sin progresión (SSP) del tratamiento combinado con ibrutinib para el CCR y el carcinoma urotelial
Evaluar la TRG del tratamiento combinado con ibrutinib para el adenocarcinoma gástrico y el ARC

E.2.2

Secondary objectives of the trial

Phase 1b:
Assess the overall response rate of ibrutinib combination therapy in each cohort
Assess the safety and tolerability of ibrutinib combination therapy in each cohort
Assess the disease control rate of ibrutinib combination therapy in each cohort
Evaluate the pharmacokinetics of ibrutinib combination therapy in each cohort
Phase 2:
Assess the PFS of ibrutinib combination therapy in gastric adenocarcinoma and CRC
Assess the ORR of ibrutinib combination therapy in RCC and urothelial carcinoma
Assess the DCR of ibrutinib combination therapy in each cohort
Assess the median overall survival (OS) of ibrutinib combination therapy in each cohort
Assess the safety and tolerability of ibrutinib combination therapy in each cohort

Objetivos secundarios
Fase 1b:
Evaluar la tasa de respuesta global (TRG) del tratamiento combinado con ibrutinib en cada cohorte.
Evaluar la seguridad y la tolerancia del tratamiento combinado con ibrutinib en cada cohorte.
Evaluar la tasa de control de la enfermedad (TCE) del tratamiento combinado con ibrutinib en cada cohorte.
Evaluar la farmacocinética (FC) del tratamiento combinado con ibrutinib en cada cohorte.
Fase 2:
Evaluar la SSP del tratamiento combinado con ibrutinib para el adenocarcinoma gástrico y el ACR.
Evaluar la TRG del tratamiento combinado con ibrutinib para el CCR y el carcinoma urotelial.
Evaluar la TCE del tratamiento combinado con ibrutinib en cada cohorte
Evaluar la mediana de la supervivencia global (SG) del tratamiento combinado con ibrutinib en cada cohorte
Evaluar la seguridad y la tolerancia del tratamiento combinado con ibrutinib en cada cohorte

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Histologically confirmed:
RCC (clear cell)
Urothelial carcinoma (transitional cell)
Gastric or GEJ adenocarcinoma
K-RAS wild-type EGFR expressing CRC
2. One or more measurable lesions per RECIST 1.1 criteria.
3. The following prior criteria should be followed:
Metastatic RCC: minimum of 1 and maximum of 4 prior regimens, one or more of which must have included a VEGF-TKI
Advanced (locally recurrent and/or metastatic) urothelial carcinoma: minimum of 1 and maximum of 2 prior regimens, one of which must be a cisplatin based regimen
Advanced (locally recurrent and or metastatic) gastric or GEJ adenocarcinoma: minimum of 1 and maximum of 3 prior regimens one of which must be a fluoropyrimidine based regimen
Metastatic CRC: minimum of 2 and maximum of 4 prior regimens, which must have included both an irinotecan and an oxaliplatin based regimen or unable to tolerate irinotecan chemotherapy
4. Each subject must be assessed by the investigator to be a suitable candidate for treatment with everolimus, docetaxel, paclitaxel or cetuximab, as appropriate according to their type of cancer.
5. Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 3 days of the first dose of study drug and agree to use dual methods of contraception during the study and for 1 month following the last dose with study drug. Post-menopausal females (>45 years old and without menses for >1 year) and surgically sterilized females are exempt from this criterion.
6. Male subjects must use an effective barrier method of contraception during the study and for 3 months following the last dose if sexually active with a female of childbearing potential.
Laboratory
7. Adequate hematologic function (independent of transfusion and growth factor support for at least 7 days prior to enrollment, with the exception of pegylated G-CSF (pegfilgrastim) and darbopoeitin which require at least 14 days prior to enrollment defined as:
Absolute neutrophil count more than 1500 cells/mm3 (1.5 x 109/L)
Platelet count >80,000 cells/mm3 (80 x 109/L)
Hemoglobin >8.0 g/dL
8. Adequate hepatic and renal function defined as:
Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) smaller or equal than 5.0 x upper limit of normal (ULN) if liver metastases, or less than 3 x ULN without liver metastases
Alkaline phosphatase less than 3.0 x ULN or ?5.0 x ULN if liver or bone metastases present
Bilirubin smaler or equal 1.5 x ULN (unless bilirubin rise is due to Gilbert s syndrome or of non-hepatic origin, such as hemolysis) with the exception of patients in the gastric adenocarcinoma cohort where docetaxel is administered, these patients must have bilirubin within normal limits (WNL).
Estimated Creatinine Clearance greater than or equal 30 mL/min (Cockcroft-Gault)
Demographic
9. Men and women greater than or equal 18 years of age
10. Eastern Cooperative Oncology Group (ECOG) performance status 0 1. For subjects with RCC or CRC, an ECOG score of 2, may be acceptable if approved by the medical monitor.

Relacionados con la enfermedad
1.Confirmado histológicamente:
CCR (células claras)
Carcinoma urotelial (células transicionales)
Adenocarcinoma gástrico o UGE
EFGR de K-RAS de tipo salvaje que expresa ACR
2.Una o más lesiones medibles según los criterios de RECIST 1.1.
3.Se deben cumplir los siguientes criterios previos:
CCR metastásico: mínimo de 1 y un máximo de 4 pautas posológicas anteriores, una o más de las cuales debe haber incluido VEGF-TKI
Carcinoma urotelial avanzado (localmente recurrente y/o metastásico): mínimo de 1 y máximo de 2 pautas posológicas anteriores, una de las cuales debe incluir cisplatino
Carcinoma gástrico o de UGE avanzado (localmente recurrente y/o metastásico): mínimo de 1 y máximo de 3 pautas posológicas anteriores, una de las cuales debe incluir fluoropirimidina
CCR metastásico: mínimo de 2 y máximo de 4 pautas posológicas anteriores, que deben haber incluido una con irinotecán y oxaliplatino, o incapacidad para tolerar la quimioterapia con irinotecán
4.El investigador debe evaluar a todos los sujetos para confirmar su idoneidad como candidatos para el tratamiento con everolimus, docetaxel, paclitaxel o cetuximab, según corresponda a su tipo de cáncer.
5.Las mujeres en edad fértil deben tener una prueba de embarazo en suero u orina negativa a 3 días de la primera dosis del fármaco en estudio y acceder a usar métodos duales de anticoncepción durante el estudio y durante 1 mes después de la administración de la última dosis del fármaco en estudio. Las mujeres posmenopáusicas
(mayores de 45 años de edad y sin menstruación durante más de 1 año) y las mujeres esterilizadas quirúrgicamente quedan exentas de este criterio.
6.Los varones deben usar un método de barrera anticonceptivo eficaz durante el estudio y durante 3 meses después de la administración de la última dosis si es sexualmente activo con una mujer fértil.
Analítica
7. Función hematológica adecuada (independiente del apoyo con transfusiones y factor de crecimiento durante al menos 7 días antes de la inclusión, a excepción de G-CSF pegilado [pegfilgrastim] y darbopoyetina, que se requiere al menos 14 días antes de la inclusión) y que se define como:
Recuento absoluto de neutrófilos más de 1500 células/mm3 (1,5 x 109/L)
Recuento plaquetario más de 80.000 células/mm3 (80 x 109/L)
Hemoglobina más de 8,0 g/dl
8.Función hepática y renal adecuada, definida como:
Aspartato transaminasa sérica (AST) y/o alanina transaminasa (ALT)menos o igual a 5,0 veces el límite superior de la normalidad (LSN) si hay metástasis hepáticas, o menos o igual a 3 veces el LSN si no hay metástasis hepáticas
Fosfatasa alcalina menos de 3,0 veces el LSN o menor o igual a 5,0 veces el LSN si hay metástasis hepáticas u óseas
Bilirrubina monos o gual de 1,5 veces el LSN (a menos que el aumento de bilirrubina sea debido al síndrome de Gilbert o tenga un origen no hepático, como hemólisis) con la excepción de los pacientes de la cohorte de adenocarcinoma gástrico en los que se administra docetaxel, la bilirrubina de estos pacientes debe encontrarse dentro de los límites normales (DLN).
Aclaramiento de creatinina estimado mayor o igual a 30 ml/min (Cockcroft-Gault)
Demografía
9.Hombres y mujeres de más de 18 años de edad
10.Estado funcional del Grupo Oncológico Cooperativo del Este (ECOG) 0 1. Para sujetos con CCR o ACR, una puntuación ECOG de 2 puede ser aceptable si es aprobada por el monitor médico.

E.4

Principal exclusion criteria

1. Anticancer therapy (chemotherapy, antibody therapy, molecular targeted therapy, or investigational agent) within 28 days of the first dose of study drug (6 weeks for nitrosureas, mitomycin C, or antibody based therapies)
2. Prior treatment with:
Everolimus or temsirolimus (RCC cohort)
Any taxane (urothelial carcinoma cohort)
Any taxane (gastric adenocarcinoma cohort)
Cetuximab or panitumumab (CRC cohort)
3. Prior radiotherapy to measurable lesion, unless documented progression has occurred post-irradiation
4. Lack of recovery from previous therapeutic radiation (persistence of Grade greater than or equal than 2 radiation-related toxicity), or planned radiation therapy during the study period
Concurrent Conditions
5. Any uncontrolled active systemic infection including any infection requiring systemic IV treatment which was completed minor or equal than 7 days before Cycle 1 Day 1.
6. History of other malignancies, except:
Malignancy treated with curative intent and with no known active disease present for mayor than or equal 3 years before the first dose of study drug and felt to be at low risk for recurrence by investigator
Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
Adequately treated carcinoma in situ without current evidence of disease
7. Prior treatment with ibrutinib or other BTK inhibitor
8. ALT and/or AST more than 1.5 x ULN and alkaline phosphatase more than 2.5 x ULN (gastric adenocarcinoma cohort only)
9. Known allergy or hypersensitivity to ibrutinib or any other component of combination therapy, including polysorbate 80 or Cremophor® EL (polyoxyethylated castor oil)
10. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 4.03), grade 0 or 1
11. Known bleeding disorders (eg, von Willebrand?s disease) or hemophilia
12. Grade mayor than or equal 3 sensory peripheral neuropathy
13. History of stroke or intracranial hemorrhage within 6 months prior to enrollment
14. Known brain or leptomeningeal disease (CT or MRI scan of the brain required only in case of clinical suspicion of central nervous system involvement)
15. Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV)
Patients who are positive for hepatitis B core antibody, hepatitis B surface antigen or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.
16. Major surgery within 4 weeks of first dose of study drug
17. Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator s opinion, could compromise the subject s safety or put the study outcomes at undue risk
18. Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure, as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to enrollment
19. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction
20. Unable to swallow capsules and/or tablets
21. Concomitant use of warfarin or other Vitamin K antagonists
22. Requires treatment with a strong cytochrome P450 (CYP) 3A4/5 inhibitor
23. Lactating or pregnant
24. Unwilling or unable to participate in all required study evaluations and procedures.
25. Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations).

Relacionados con la enfermedad
1.Tratamiento contra el cáncer (quimioterapia, terapia con anticuerpos, terapia molecular dirigida o producto en investigación) en los 28 días anteriores a la administración de la primera dosis del fármaco
(6 semanas para nitrosureas, mitomicina C, o terapias con anticuerpos)
2.Tratamiento previo con:
Everolimus o temsirolimus (cohorte de CCR)
Cualquier taxano (cohorte de carcinoma urotelial)
Cualquier taxano (cohorte de adenocarcinoma gástrico)
Cetuximab o panitumumab (cohorte de ACR)
3.Radioterapia anterior a la lesión medible, a menos que la progresión documentada se haya producido después de la irradiación
4.No recuperación de la radiación terapéutica anterior (persistencia de la toxicidad relacionada con la radiación de grado mayor o igual de 2), o radioterapia programada durante el período del estudio
Afecciones concurrentes
5.Cualquier infección sistémica activa no controlada, incluyendo cualquier infección que requiera tratamiento IV sistémico finalizado menos o 7 días antes del Día 1 del Ciclo 1.
6.Antecedentes de otras neoplasias malignas, excepto:
Neoplasias malignas tratadas con intención curativa y sin enfermedad activa conocida presente durante más o 3 años antes de la administración de la primera dosis del fármaco en estudio que el investigador considere que tienen un riesgo de recurrencia bajo
Cáncer de piel no melanocítico adecuadamente tratado o léntigo maligno sin evidencia de enfermedad
Carcinoma in situ adecuadamente tratado sin evidencia actual de enfermedad
7.Tratamiento previo con ibrutinib u otro inhibidor de la tirosina cinasa de Bruton (BTK)
8.ALT y/o AST >1,5 x LSN y fosfatasa alcalina >2,5 x LSN (cohorte de adenocarcinoma gástrico solamente)
9.Alergia o hipersensibilidad a ibrutinib o a cualquier otro componente del tratamiento combinado, incluyendo polisorbato 80 o Cremophor® (aceite de ricino polioxietilado)
10.Toxicidades no resueltas de tratamientos contra el cáncer anteriores, definido como la presencia de acontecimientos adversos de grado 0 o 1 según los criterios terminológicos comunes (CTCAE, versión 4.03) no resueltos
11.Trastornos hemorrágicos conocidos (por ejemplo, enfermedad de von Willebrand) o hemofilia
12.Neuropatía periférica sensitiva de grado ?3
13.Antecedentes de ictus o hemorragia intracraneal en los 6 meses anteriores a la inclusión.
14.Enfermedad cerebral o leptomeníngea conocida (la exploración por TAC o RMN del cerebro solo es necesaria en caso de sospecha clínica de afectación del sistema nervioso central)
15.Antecedentes de virus de la inmunodeficiencia humana (VIH) o virus de la hepatitis C (VHC) o virus de la hepatitis B (VHB) activo
Los pacientes positivos para el anticuerpo central de la hepatitis B, el antígeno de superficie de la hepatitis B o los anticuerpos de la hepatitis C deben tener una prueba de reacción en cadena de la polimerasa (PCR) negativa antes de la inclusión. Los sujetos con resultado positivo de la PCR serán excluidos.
16.Cirugía importante en las 4 semanas anteriores a la administración de la primera dosis del fármaco en estudio
17.Cualquier enfermedad potencialmente mortal, condición médica o disfunción de un sistema orgánico que, en opinión del investigador, pueda comprometer la seguridad del sujeto o poner en un peligro indebido los resultados del estudio
18.Enfermedad cardiovascular actualmente activa y clínicamente significativa, como una arritmia no controlada o insuficiencia cardíaca congestiva de clase 3 o 4 según la definición de clasificación funcional de la Asociación del Corazón de Estados Unidos (New York Heart Association); o antecedentes de infarto de miocardio, angina inestable, o síndrome coronario agudo en los 6 meses anteriores a la inclusión
19.Síndrome de malabsorción, enfermedad que afecte significativamente a la función gastrointestinal, o enfermedad inflamatoria intestinal sintomática o colitis ulcerosa, u obstrucción intestinal parcial o total
20.Incapacidad para tragar las cápsulas y/o comprimidos
21.Uso concomitante de warfarina u otros antagonistas de la vitamina K
22.Necesidad de tratamiento con un inhibidor potente del citocromo P450 (CYP) 3A4/5
23.Mujeres embarazadas o en período de lactancia
24.Rechazo o incapacidad para participar en todas las evaluaciones y procedimientos requeridos en el estudio.
25.Incapacidad para entender el propósito y los riesgos del estudio y para proporcionar un formulario de consentimiento informado (FCI) firmado y fechado y la autorización para el uso de información sanitaria protegida (de acuerdo con las normativas de privacidad nacional y local del sujeto).

E.5 End points

E.5.1

Primary end point(s)

E.5.1.1

Timepoint(s) of evaluation of this end point

A dose level review committee (DLRC) will evaluate the safety data at the completion of the initial Phase 1b portion in each cohort to determine the RP2D, prior to continuing with enrollment into the Phase 2 portion.
The DLT observation period will encompass 21 days after the initiation of combination therapy.
Phase 1b of the study will follow a 6+3 dose de-escalation design. In any given cohort if 2 subjects within the initial group of 6 subjects experience a DLT, an additional 3 subjects will be enrolled at the same dose level. If 3 or more of 9 subjects in total experience a DLT, dose de escalation will occur and an additional 6 subjects will be treated at a lower dose level

Un comité de revisión del nivel de dosis (CRND) evaluará los datos de seguridad al finalizar la parte inicial de la Fase 1b inicial en cada cohorte para determinar la DRF2 antes de continuar con la inscripción en la Fase 2.
El período de observación de la TLD durará 21 días después del inicio del tratamiento combinado.
La Fase 1b del estudio seguirá un diseño de reducción de dosis de 6 + 3. En cualquier cohorte dada, si 2 sujetos del primer grupo de 6 sujetos experimentan una TLD, se inscribirán otros 3 sujetos con el mismo nivel de dosis. Si 3 o más de 9 sujetos en total experimentan una TLD, se realizará una reducción de la dosis y otros 6 sujetos serán tratados con un nivel de dosis inferior

E.5.2

Secondary end point(s)

Phase 1b:
Secondary objectives:
To assess the overall response rate (ORR) of ibrutinib combination therapy in each cohort
To assess the safety and tolerability of ibrutinib combination therapy in each cohort
To assess the disease control rate (DCR) of ibrutinib combination therapy in each cohort
To evaluate the pharmacokinetics (PK) of ibrutinib combination therapy in each cohort

Phase 2:
Secondary Objectives:
To assess the PFS of ibrutinib combination therapy in gastric adenocarcinoma and CRC
To assess the ORR of ibrutinib combination therapy in RCC and urothelial carcinoma
To assess the DCR of ibrutinib combination therapy in each cohort
To assess the median overall survival (OS) of ibrutinib combination therapy in each cohort
To assess the safety and tolerability of ibrutinib combination therapy in each cohort
Exploratory Objectives:
Biomarker analysis for response and resistance to ibrutinib based therapy
To assess ITK occupancy during ibrutinib treatment in each cohort
To evaluate the pharmacokinetics (PK) of ibrutinib combination therapy in each cohort

Fase 1b:
Objetivos secundarios:
Evaluar la tasa de respuesta global (TRG) del tratamiento combinado con ibrutinib en cada cohorte
Evaluar la seguridad y la tolerancia del tratamiento combinado con ibrutinib en cada cohorte
Evaluar la tasa de control de la enfermedad (TCE) del tratamiento combinado con ibrutinib en cada cohorte
Evaluar la farmacocinética (FC) del tratamiento combinado con ibrutinib en cada cohorte

Fase 2
Objetivos secundarios:
Evaluar la SSP del tratamiento combinado con ibrutinib para el adenocarcinoma gástrico y el ACR
Evaluar la TRG del tratamiento combinado con ibrutinib para el CCR y el carcinoma urotelial
Evaluar la TCE del tratamiento combinado con ibrutinib en cada cohorte
Evaluar la mediana de la supervivencia global (SG) del tratamiento combinado con ibrutinib en cada cohorte
Evaluar la seguridad y la tolerancia del tratamiento combinado con ibrutinib en cada cohorte

E.5.2.1

Timepoint(s) of evaluation of this end point

RCC: A single interim analysis for futility will take place when the 25th subject has completed 6 months of follow-up. The proportion of subjects that are PFS event-free at 6 months will be assessed along with other safety and efficacy data in making the determination if the study should continue.
Urothelial carcinoma:
A single interim analysis for futility will take place when the 25th subject has completed 4 months of follow-up. The proportion of subjects PFS event-free at 4 months will be assessed along with other safety and efficacy data in making the determination if the study should continue.
Gastric adenocarcinoma and CRC:The gastric adenocarcinoma and CRC cohorts employ a Simon two stage Minimax design involving the ORR endpoint.

CCR:único análisis provisional de intranscendencia cuando el 25º paciente finalice 6m de seguimiento. %de sujetos con SSP sin acontecimientos a los 6m se evaluará junto con otros datos de seg y efic para determinar si el estudio debe seguir. Carcinoma urotelial:Se realizará único análisis provisional de la intranscendencia cuando el 25ºsujeto haya finalizado los 4m de seguimiento. La proporción de sujetos con SSP sin acontecimientos a los 4m se evaluará junto con datos de seg y efic para determinar si el estudio debe seguir. Adenocarcinoma gástrico y ACR. Las cohortes emplean diseño minimax de Simon de 2etapas que implica el criterio de valoración de la TRG. Los datos que apoyen la continuación en la 2ª etapa serán la mejor tasa respuesta RC o RP combinada con otros datos de seg y efic

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

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

integrated protocol design Phase 1b/2

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

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

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

Spain

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

A subject will be considered to have completed the study if he or she has died before the end of the study, has not been lost to follow up, or has not withdrawn consent before the end of study.

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

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:

189

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

189

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

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

189

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)

All subjects, regardless of reason for discontinuation of study treatment will undergo an EOT Visit and be followed for progression (if appropriate) and survival.
If a subject shows signs of disease progression on physical examination or laboratory assessment, the subject may continue study treatment, at the discretion of the investigator, until disease progression is confirmed by radiologic assessment (eg, CT/MRI) according to RECIST 1.1 criteria.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-02-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-02-04

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

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Clinical trials