Clinical Trials Register

Summary
EudraCT Number:	2018-001811-59
Sponsor's Protocol Code Number:	D933RC00001
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:	2019-01-18
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

Spain - AEMPS

A.2

EudraCT number

2018-001811-59

A.3

Full title of the trial

A Phase III, Randomized, Open-Label, Multi-Center, Global Study to Determine the Efficacy and Safety of Durvalumab in Combination with Gemcitabine+Cisplatin for Neoadjuvant Treatment Followed by Durvalumab Alone for Adjuvant Treatment in Patients with Muscle-Invasive Bladder Cancer

Ensayo fase III, aleatorizado, abierto, multicéntrico e internacional para determinar la eficacia y la seguridad de durvalumab en combinación con gemcitabina + cisplatino como tratamiento neoadyuvante seguido de durvalumab en monoterapia como tratamiento adyuvante en pacientes con cáncer de vejiga músculo invasivo (NIAGARA)

A.3.1

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

This is a Global Study to Determine the Efficacy and Safety of Durvalumab in Combination with Gemcitabine+Cisplatin for Neoadjuvant Treatment followed by Durvalumab Alone for Adjuvant Treatment in Patients with Muscle-Invasive Bladder Cancer

Este es un Estudio Global para determinar la eficacia y la seguridad de durvalumab en combinación con gemcitabina + cisplatino como tratamiento neoadyuvante seguido de durvalumab en monoterapia como tratamiento adyuvante en pacientes con cáncer de vejiga músculo invasivo

A.3.2

Name or abbreviated title of the trial where available

NIAGARA

A.4.1

Sponsor's protocol code number

D933RC00001

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	AstraZeneca AB
B.1.3.4	Country	Sweden
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	AstraZeneca AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AstraZeneca Clinical
B.5.2	Functional name of contact point	Study Information Center
B.5.3	Address:
B.5.3.1	Street Address	NA
B.5.3.2	Town/ city	NA
B.5.3.3	Post code	NA
B.5.3.4	Country	United States
B.5.4	Telephone number	1877240-9479
B.5.6	E-mail	information.center@astrazeneca.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	durvalumab
D.3.2	Product code	MEDI4736
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	durvalumab
D.3.9.1	CAS number	1428935607
D.3.9.2	Current sponsor code	MEDI4736
D.3.9.3	Other descriptive name	MEDI4736
D.3.9.4	EV Substance Code	SUB176342
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	50
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	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	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with histologically or cytologically documented muscle-invasive transitional cell carcinoma (TCC) of the bladder

Pacientes con carcinoma de vejiga de células transicionales (CCT) documentado histológicamente o citológicamente

E.1.1.1

Medical condition in easily understood language

Muscle Invasive Bladder Cancer (T2-T4a) in stage II and IIIA without lymph node involvement

Cáncer de Vejiga Músculo Invasivo (T2-T4a) en estadío II y IIIA sin afectación de los ganglios linfáticos

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10005010
E.1.2	Term	Bladder cancer stage II
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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10005011
E.1.2	Term	Bladder cancer stage III
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess efficacy of investigational product in patients with MIBC using pCR and EFS

Evaluar la eficacia del producto en investigación en pacientes con cáncer de vejiga músculo invasivo (CVIM) usando RCap y SSE

E.2.2

Secondary objectives of the trial

To assess efficacy and safety of investigational product in patients with MIBC using the following:

EFS, pCR, EFS24

Proportion of patients who achieve <P2

Proportion of subjects with cystectomy

Metastasis-free survival and disease-specific survival

OS

DFS

Pharmacokinetic and Immunogenicity

Safety and tolerability profile

Evaluar la eficacia y seguridad del producto en investigación en pacientes con CVIM usando lo siguiente:

SSE, RCap, SSE24

Proporción de pacientes que alcanzan <P2

Proporción de sujetos con cistectomía

Supervivencia sin metástasis y supervivencia específica de la enfermedad

SG

Supervivencia sin enfermedad

Farmacocinética e Inmunogenicidad

Seguridad y perfil de seguridad

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patient resectable muscle-invasive bladder cancer with clinical stage T2N0M0-T4aN0M0 with transitional cell histology;

Patients must be planning to undergo a radical cystectomy at the time of randomization;

Patients who have not received prior systemic chemotherapy or immunotherapy for treatment of MIBC;

ECOG performance status of 0 or 1 at enrollment.

Availability of tumor sample prior to study entry;

Must have a life expectancy of at least 12 weeks at randomization.

Paciente con cáncer de vejiga músculo invasivo resecable con estadío clínico T2N0M0-T4aN0M0 con histología de células transicionales;

Los pacientes deben tener programado someterse a una cistectomía radical en el momento de la aleatorización;

Los pacientes que no hayan recibido quimioterapia o inmunoterapia sistémica previa para el tratamiento del CVIM;

Puntuación ECOG (Eastern Cooperative Oncology Group) de 0 o 1 en el reclutamiento.

Disponibilidad de muestra del tumor antes de la entrada en el estudio;

Debe tener una esperanza de vida de al menos 12 semanas en la aleatorización.

E.4

Principal exclusion criteria

Evidence of lymph node involvement or metastatic disease at the time of screening.

Contra-indication to any of the study drugs

Requires immunosuppression medication for a concomitant condition

Active or prior documented autoimmune or inflammatory disorders

Evidencia de implicación de los ganglios linfáticos o enfermedad metastásica en el momento de la selección.

Contraindicación a cualquiera de los medicamentos del estudio

Requiera medicación de inmunosupresión para la condición concomitante

Alteraciones autoinmunes o inflamatorias activas o documentadas previamente.

E.5 End points

E.5.1

Primary end point(s)

pCR
EFS

RCap
SSE

E.5.1.1

Timepoint(s) of evaluation of this end point

Approximately 36 months (pCR)
Up to 48 months (EFS)

Aproximadamente 36 meses (RCap)
Hasta 48 meses (SSE)

E.5.2

Secondary end point(s)

EFS, pCR, EFS24

Proportion of patients who achieve <P2

Proportion of subjects with cystectomy

Metastasis-free survival and disease-specific survival

OS

DFS

Pharmacokinetic and Immunogenicity

Safety and tolerability profile

SSE, RCap, SSE24

Proporción de pacientes que alcanzan <P2

Proporción de sujetos con cistectomía

Supervivencia sin metástasis y supervivencia específica de la enfermedad

SG

Supervivencia sin enfermedad

Farmacocinética e Inmunogenicidad

Seguridad y perfil de tolerancia

E.5.2.1

Timepoint(s) of evaluation of this end point

Approximately 36 months (pCR; Proportion of patients who achieve <P2)
Up to 24 months (EFS24)
Up to 84 months (OS; Safety and tolerability profile)
Up to 48 months (Other endpoints)

Aproximadamente 36 meses (RCap, proporción de pacientes que alcanzan <P2)
Hasta 24 meses (SSE24)
Hasta 84 meses (SG; Seguridad y perfil de tolerancia)
Hasta 48 meses (Otras variables)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Quality of Life

Calidad de vida

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

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

Belgium

Brazil

Canada

Chile

Czech Republic

France

Germany

Israel

Japan

Korea, Republic of

Netherlands

Philippines

Poland

Russian Federation

Taiwan

Turkey

United Kingdom

United States

Vietnam

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

LSLV

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

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:

525

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

525

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Information not present in EudraCT

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

377

F.4.2.2

In the whole clinical trial

1050

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)

After final analysis no study drug will be provided

No se suministrará medicación del estudio después del análisis final

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

2019-06-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-05-29

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

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