Clinical Trials Register

Summary
EudraCT Number:	2013-005085-19
Sponsor's Protocol Code Number:	CBGJ398X2204
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-05-22
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

2013-005085-19

A.3

Full title of the trial

A phase II multicenter, single arm study of oral BGJ398 in adult patients with advanced or metastatic cholangiocarcinoma with FGFR2 gene fusions or other FGFR genetic alterations who failed or are intolerant to platinum-based chemotherapy

Estudio fase II, multicéntrico, con un único brazo de tratamiento, de BGJ398 oral en pacientes adultos con colangiocarcinoma avanzado o metastásico, con fusiones del gen FGFR2 u otras alteraciones genéticas del FGFR que han progresado o que son intolerantes a quimioterapia basada en platino

A.3.1

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

This is a multi-center, open label, single arm phase II study evaluating BGJ398 anti-tumor activity in advanced or metastatic cholangiocarcinoma patients with FGFR genetic alterations.

Estudio con un solo brazo de tratamiento de BGJ398 en pacientes adultos con colangiocarcinoma avanzado o metastásico

A.4.1

Sponsor's protocol code number

CBGJ398X2204

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	Novartis Farmacéutica, S.A.
B.1.3.4	Country	Spain
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	Novartis Pharma Services AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Farmacéutica, S.A.
B.5.2	Functional name of contact point	Departamento Médico Oncología (GMO)
B.5.3	Address:
B.5.3.1	Street Address	Gran Vía de les Corts Catalanes, 764
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08013
B.5.3.4	Country	Spain
B.5.4	Telephone number	34900353036
B.5.5	Fax number	34932479903
B.5.6	E-mail	eecc.novartis@novartis.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.3.2	Product code	BGJ398
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BGJ398
D.3.9.1	CAS number	BGJ398
D.3.9.2	Current sponsor code	BGJ398
D.3.9.3	Other descriptive name	BGJ398
D.3.9.4	EV Substance Code	SUB31319
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	25
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	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.3.2	Product code	BGJ398
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BGJ398
D.3.9.1	CAS number	BGJ398
D.3.9.2	Current sponsor code	BGJ398
D.3.9.3	Other descriptive name	BGJ398
D.3.9.4	EV Substance Code	SUB31319
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	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	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	Renagel
D.2.1.1.2	Name of the Marketing Authorisation holder	Genzyme Europe, Bv
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Renagel
D.3.2	Product code	Renagel
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	SEVELAMER
D.3.9.1	CAS number	52757-95-6
D.3.9.2	Current sponsor code	Renagel
D.3.9.3	Other descriptive name	Renagel
D.3.9.4	EV Substance Code	SUB04381MIG
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	800
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

advanced or metastatic cholangiocarcinoma
FGFR2 gene fusion,
FGFR genetic alteration

colangiocarcinoma avanzado o metastásico
Fusión de genes FGFR2,
Alteración genética FGFR

E.1.1.1

Medical condition in easily understood language

biliary tract cancer

cáncer del tracto biliar

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	17.0
E.1.2	Level	PT
E.1.2	Classification code	10008593
E.1.2	Term	Cholangiocarcinoma
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

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the efficacy of single agent BGJ398 in patients with advanced or metastatic cholangiocarcinoma with FGFR2 gene fusions/translocations or other FGFR genetic alterations assessed by investigator as per RECIST v1.1.

Evaluar la eficacia de BGJ398 en monoterapia en pacientes con colangiocarcinoma avanzado o metastásico con translocaciones/fusiones del gen FGFR2 u otras alteraciones genéticas del FGFR medido por el investigador a través de la tasa de respuesta global según los RECIST v1.1.

E.2.2

Secondary objectives of the trial

-To further evaluate the efficacy of single agent BGJ398 as measured by
progression free survival, best overall response, disease control rate,
overall survival assessed by investigator as per RECIST 1.1
- To characterize the safety and tolerability of single agent BGJ398 by the type, frequency and severity of AEs & SAEs.
- To determine selected trough and 2-hr plasma concentrations of BGJ398

Evaluar mejor la eficacia de BGJ398 en monoterapia, medido con la supervivencia libre de progresión, mejor respuesta global, tasa de control de la enfermedad, supervivencia global, evaluado por el investigador, según los RECIST 1.1
Caracterizar la seguridad y la tolerabilidad de BGJ398 en monoterapia por tipo, frecuencia y severidad de AAs y de AAGs.
Determinar las concentraciones seleccionadas valle y a las 2 horas en plasma de BGJ398 y de sus metabolitos

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Patients with histologically or cytologically confirmed cholangiocarcinoma at the time of diagnosis.
- Patients must have received at least one prior regimen containing gemcitabine with or without cisplatin for advanced or metastatic disease. Patient must have evidence of progressive disease following prior regimen.
Other protocol defined criteria may apply

Pacientes con colangiocarcinoma confirmado citológica o histológicamente en el momento del diagnóstico.
Se requiere documentación por escrito de determinación del laboratorio local o central de translocaciones/fusiones del gen FGFR2 u otras alteraciones genéticas de FGFR para preselección. Los pacientes que se identifique que presentan otras alteraciones genéticas de FGFR que no sean fusiones del gen FGFR2 pueden ser elegibles, dependiendo de acuerdo entre Novartis y el investigador.
Los pacientes deberán haber recibido por lo menos un régimen previo que contenga gemcitabina con o sin cisplatino para la enfermedad avanzada o metastásica. Los pacientes deberán presentar evidencia de enfermedad progresiva tras el régimen previo.
Estado funcional del ECOG ? 1 (los pacientes con estado funcional del ECOG de 2 pueden considerarse en una base individualizada tras discusión con Novartis).

E.4

Principal exclusion criteria

- Prior or current treatment with an FGFR inhibitor
- insufficient organ function ?ANC < 1,000/mm3 [1.0 x 10E9/L] ?Platelets < 75,000/mm3 [75 x 10E9/L] ?Hemoglobin < 9.0 g/dL ?Total bilirubin > 1.5x ULN ?AST/SGOT and ALT/SGPT > 2.5x ULN (AST and ALT > 5x ULN in the presence of liver metastases) ?Serum creatinine > ULN and/or calculated
or measured creatinine clearance < 75% LLN ?Inorganic phosphorus outside of normal limits ?Total and ionized serum calcium outside of normal limits
Other protocol defined criteria may apply

Tratamiento previo o actual con un inhibidor de FGFR.
Evidencia actual de queratopatía/alteración de la retina o de la córnea significativa incluyendo pero no limitado a, queratopatía en banda/bullosa, abrasión corneal, inflamación/ulceración, queratoconjuntivitis, confirmado con examen oftalmológico.
Antecedentes y/o evidencia actual de calcificación del tejido extensivo incluyendo, pero no limitado a, el tejido blando, los riñones, el intestino, el miocardio y el pulmón, con la excepción de ganglios linfáticos calcificados, calcificaciones mínimas del parénquima pulmonar y calcificación coronaria asintomática.
Deterioro de la función gastrointestinal (GI) o enfermedad GI que pueda alterar significativamente la absorción de BGJ398 oral (por ejemplo, enfermedades ulcerosas, náuseas incontroladas, vómitos, diarrea, síndrome de mala absorción, resección del intestino delgado).
Antecedentes y/o evidencia actual de alteraciones endocrinas de homeostasis del calcio/fosfato, por ejemplo, alteraciones paratiroideas, antecedentes de paratiroidectomía, lisis tumoral, calcinosis tumoral, etc.
Se excluirán pacientes que reciban tratamiento concurrentemente con agentes que se conozca que son inhibidores o inductores potentes de CYP3A4 y medicaciones que aumenten la concentración de calcio y/o fósforo en suero (remítase al Suplemento 2 para la lista de medicaciones prohibidas).

E.5 End points

E.5.1

Primary end point(s)

Overall response rate (ORR) is defined as the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR), as
per RECIST version 1.1.

Tasa de respuesta global (ORR) se define como la proporción de pacientes con una mejor respuesta global de respuesta completa (CR) o respuesta parcial (PR), como
por RECIST versión 1.1.

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline, then every 8 weeks, until disease progression or study discontinuation

Línea de base y posteriormente cada 8 semanas hasta la progresión de la enfermedad o de la interrupción del estudio

E.5.2

Secondary end point(s)

1- Overall survival
2- Progression free survival
3- Best overall response
4- Disease control rate
5- Number of participants with adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability
6-Selected trough and 2-hr Plasma concentration profile

1 - La supervivencia global
2 - supervivencia libre de progresión
3 - Mejor respuesta global
4 - Tasa de Control de enfermedades
5 - Número de participantes con aconteciimientos adversos (EA) y los acontecimientos adversos graves (AAG) como una medida de seguridad y tolerabilidad
A través de 6 seleccionados y 2-hr perfil de concentración de plasma

E.5.2.1

Timepoint(s) of evaluation of this end point

1- Every 4 months for one year after discontinuation of study treatment
2- Baseline, then every 8 weeks until disease progression or the initiation of subsequent anticancer therapies or death whichever occurs first
3- Baseline, then every 8 weeks, until disease progression or study discontinuation
4- Baseline, then every 8 weeks, until disease progression or study discontinuation
5- Starting from date of signing the consent form to 30 days afer the last
dose
6- From First dose of study treatment
to study discontinuation

1 - Cada 4 meses durante un año después de la interrupción del tratamiento del estudio
2 - Línea de Base y posteriormente cada 8 semanas hasta la progresión de la enfermedad o el inicio de las terapias contra el cáncer posteriores o muerte que ocurra primero
3 - Línea de Base y posteriormente cada 8 semanas hasta la progresión de la enfermedad o de la interrupción del estudio
4 - Línea de Base y posteriormente cada 8 semanas hasta la progresión de la enfermedad o de la interrupción del estudio
5 - A partir de la fecha de la firma del formulario de consentimiento a 30 días después de la última dosis

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

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

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

Belgium

France

Germany

Italy

Japan

Korea, Republic of

Russian Federation

Singapore

Spain

Taiwan

Thailand

Turkey

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

End of study is defined as the time when the last patient completes the survival follow-up as described in the protocol or when the last patient on study has expired, been lost to follow up, or withdraws consent, whichever occurs first or when the study is terminated early.

Fin del estudio se define como el momento en que el último paciente completa la supervivencia de seguimiento tal como se describe en el protocolo o cuando el último paciente en el estudio ha caducado, se pierde durante el seguimiento o retira su consentimiento, lo que ocurra primero, o cuando el estudio se termina antes de tiempo.

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 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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

F.4.2.2

In the whole clinical trial

F.5

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

none

ninguno

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

2014-06-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-06-04

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-02-07

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