Clinical Trials Register

Summary
EudraCT Number:	2013-002844-10
Sponsor's Protocol Code Number:	CA209-032
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:	2013-10-22
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

2013-002844-10

A.3

Full title of the trial

A Phase 1/2, Open-label Study of Nivolumab Monotherapy or Nivolumab combined with Ipilimumab in Subjects with Advanced or Metastatic Solid Tumors

Estudio fase 1/2, abierto, de nivolumab en monoterapia o nivolumab combinado con ipilimumab en sujetos con tumores sólidos avanzados o metastásicos

A.3.1

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

A Phase 1/2, Open-label Study of Nivolumab Monotherapy or Nivolumab combined with Ipilimumab in Subjects with Advanced or Metastatic Solid Tumors

Estudio fase 1/2, abierto, de nivolumab en monoterapia o nivolumab combinado con ipilimumab en sujetos con tumores sólidos avanzados o metastásicos

A.4.1

Sponsor's protocol code number

CA209-032

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	EU Study Start-Up Unit
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.5.6	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	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	Nivolumab
D.3.2	Product code	BMS-936558
D.3.4	Pharmaceutical form	Solution for injection/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	NIVOLUMAB
D.3.9.4	EV Substance Code	SUB122750
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	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.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.3.1	Product name	Ipilimumab
D.3.2	Product code	BMS-734016
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 / MDX010
D.3.9.4	EV Substance Code	SUB29397
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	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

Advanced or metastatic solid tumors:
1) Triple Negative Breast Cancer (TNBC)
2) Gastric Cancer (GC)
3) Pancreatic Cancer (PC)
4) Small Cell Lung Cancer (SCLC).

Cáncer avanzado o metastásico:
1) Cáncer de mama triple negativo (CMTN)
2) Cáncer gástrico (CG)
3) Cáncer pancreático (CPan)
4) Cáncer microcítico de pulmón (CMP).

E.1.1.1

Medical condition in easily understood language

Advanced or metastatic solid tumors:
1) Triple Negative Breast Cancer (TNBC)
2) Gastric Cancer (GC)
3) Pancreatic Cancer (PC)
4) Small Cell Lung Cancer (SCLC).

Cáncer avanzado o metastásico:
1) Cáncer de mama triple negativo (CMTN)
2) Cáncer gástrico (CG)
3) Cáncer pancreático (CPan)
4) Cáncer microcítico de pulmón (CMP).

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10017758
E.1.2	Term	Gastric cancer
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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10041067
E.1.2	Term	Small cell lung cancer
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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10006187
E.1.2	Term	Breast cancer
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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10033604
E.1.2	Term	Pancreatic cancer
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 investigate the safety and efficacy of nivolumab as a single agent or in combination with ipilimumab in 4 tumor types - triple-negative breast cancer (TNBC), gastric cancer (GC), pancreatic adenocarcinoma (PC), and small cell lung cancer (SCLC).

Investigar la seguridad y eficacia de nivolumab en monoterapi o en combinación con ipilimumab en 4 tipos de tumores:
1) Cáncer de mama triple negativo (CMTN)
2) Cáncer gástrico (CG)
3) Cáncer pancreático (CPan)
4) Cáncer microcítico de pulmón (CMP).

E.2.2

Secondary objectives of the trial

? BOR (Best Overall Response)
? DOR (Duration of Response)
? Safety
? PFS (Performance Free Survival)
? OS (Overall Survival)

? Mejor respuesta global (MRG)
? Duración de la respuesta (DdR)
? Seguridad
? Supervivencia libre de progresión (SLP)
? Supervivencia global (SG)

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 Blood Sample Amendment 01 (site-specific), version 1.0, dated 16-jul-2013

The objective of this Amendment is to to permit the collection and storage of blood samples for use
in future exploratory pharmacogenetic research. Bristol-Myers Squibb will use DNA obtained from the blood sample and health information collected from the main clinical trial, CA209032 to study the association between genetic variation and drug response. Bristol-Myers Squibb may also use the DNA to study the causes and further progression of any one of the following tumor types being studied in the main protocol: Triple negative breast cancer, Gastric cancer, Pancreatic cancer, or Small Cell Lung Cancer. Samples from this study may also be used in conjunction with pharmacogenetic research results from other clinical studies to accomplish this objective

Enmienda 01 (centro especifico), versión 1.0, de 16 de julio de 2013. Muestra de sangre para análisis farmacogenético.

El objetivo de esta enmienda es permitir la recogida y la conservación de muestras de sangre para uso en estudios de investigación farmacogenética exploratorios futuros. Bristol-Myers Squibb usará el ADN obtenido de la muestra de sangre y la información de salud recogida del cuaderno de recogida de datos del ensayo clínico principal, CA209032, para estudiar la asociación entre la variación genética y la respuesta a los medicamentos. Bristol-Myers Squibb también puede usar el ADN para estudiar las causas y progresión adicional de cualquiera de los siguientes tipos de tumor que se están estudiando en el protocolo principal: cáncer de mama triple negativo, cáncer gástrico, cáncer pancreático o cáncer microcítico de pulmón. Para conseguir este objetivo pueden usarse conjuntamente muestras de este y otros estudios de investigación farmacogenética.

E.3

Principal inclusion criteria

? Subjects with histologically confirmed locally advanced or metastatic disease of the following tumor types:
? Triple Negative Breast Cancer
? Gastric Cancer
? Pancreatic Cancer
? Small Cell Lung Cancer
? Subjects must have measurable disease
? ECOG of 0 or 1.

? Sujetos con enfermedad localmente avanzada o metastásica confirmada histológicamente de los siguientes tipos tumorales:
? Cáncer de mama triple negativo
? Cáncer gástrico
? Cáncer pancreático
? Cáncer microcítico de pulmón

? Los sujetos deben tener enfermedad medible
? Estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0 ó 1.

E.4

Principal exclusion criteria

Exclusion
? Active brain metastases or leptomeningeal metastases.
? Subjects with active, known or suspected autoimmune disease.
? Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of treatment.
? Prior therapy with experimental anti-tumor vaccines; any T cell co-stimulation or checkpoint pathways, such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, including ipilimumab; or other medicines specifically targeting T cell is also prohibited.

? Metástasis cerebrales activas o metástasis leptomeníngeas.
? Sujetos con enfermedad autoinmunitaria activa, conocida o de sospecha.
? Sujetos con un problema que exija tratamiento sistémico con corticosteroides (> 10 mg de prednisona al día o equivalente) u otros medicamentos inmunosupresores dentro de los 14 días previos a la administración del fármaco del estudio.
? El tratamiento previo con vacunas antitumorales experimentales, cualquier coestimulación de linfocitos T o tratamiento dirigido a las vías del punto de control, como anticuerpos anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 o anti-CTLA-4 (incluido ipilimumab) u otros medicamentos dirigidos específicamente a los linfocitos T también están prohibidos

E.5 End points

E.5.1

Primary end point(s)

Objective response rate (ORR) in all assigned subjects as determined by the investigators. ORR is defined as the number of subjects with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of assigned subjects

El criterio de valoración principal es la tasa de respuestas objetivas (TRO) en todos los sujetos a los que se asigne tratamiento, determinada por los investigadores. La TRO se define como el número de sujetos con una mejor respuesta global (MRG) de respuesta completa (RC) o respuesta parcial (RP) dividida por el número de sujetos asignados.

E.5.1.1

Timepoint(s) of evaluation of this end point

Up until time of first documented tumor progression or death (approximately up to 17 months)

Momento en que se documente por primera vez pogresion tumoral o muerte (aproximadamente unos 17 meses)

E.5.2

Secondary end point(s)

Rate of treatment-related adverse events (AEs) leading to drug discontinuations during the first 12 weeks of treatment

Tasa de acontecimientos adversos relacionados con el tratamiento que conduzcan a la discontinuación del fármaco dentro de las primeras 12 semanas de tratamiento.

E.5.2.1

Timepoint(s) of evaluation of this end point

Up to Week 12 of treatment

Dentro de las primeras 12 semanas de tratamiento.

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

Biomarkers assessments, Outcomes Research assessments, Immunogenicity Assessments

Evaluación de los biomaradores, evaluaciones de investigación de resultados, evaluaciones de inmunogenicidad.

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

Phase I/II signal detection study to determine safety and efficacy in the 4 selected tumor types

Estudio fase 1/2 de detección de senales para determinar seguridad/eficacia en 4 tipos de tumores

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

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

Yes

E.8.1.7.1

Other trial design description

Opción de cambiar de Nivo a Nivo/Ipi para sujetos en los que la enfermedad progrese en monoterapia

option to cross over from Nivo to Nivo/ipi combination for those that progress on monotherapy arm

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

Yes

E.8.2.3.1

Comparator description

En cada tipo de tumor cada brazo se evaluara independientemente

each arm in each tumor type will be evaluated independently

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

Finland

France

Germany

Italy

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

The study will end once survival follow-up has concluded

El estudio finalizara una vez que haya concluido el seguimiento de la supervivencia.

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:

100

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

100

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

200

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 study end, subjects who continue to demonstrate clinical benefit and tolerating study drug will be eligible to receive it. Study drug will be provided via study extension, rollover study or another mechanism. BMS can terminate access to study drug if:a) marketing application rejected by responsible HA;b) study terminated due to safety concerns;c) subject can obtain medication from a government sponsored or private health program; or d) therapeutic alternatives become available in local market

Al fin del estudio, los sujetos que sigan demostrando beneficio clínico y tolerabilidad podrán recibir el fármaco, que se facilitará mediante extensión del estudio, estudio de continuación u otro mecanismo. BMS puede concluir el acceso al fármaco si: a)la solicitud de comercialización se rechaza por las autoridades sanitarias b)se termina el estudio por problemas de seguridad c) el sujeto puede obtener la medicación por un programa de salud público o privado d) aparecen alternativas terapéuticas

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

2013-11-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-10-31

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

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