Clinical Trials Register

Summary
EudraCT Number:	2015-001097-18
Sponsor's Protocol Code Number:	CA209-331
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:	2015-10-15
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

2015-001097-18

A.3

Full title of the trial

An Open-label, Randomized, Phase 3 Study of Nivolumab or Chemotherapy in Subjects with Relapsed Small-cell Lung Cancer after Platinum-based First Line Chemotherapy

Ensayo de Fase 3 abierto, aleatorizado, de Nivolumab o quimioterapia en sujetos con cáncer
de pulmón microcítico (CPM) en recaída después de quimioterapia de primera línea basada en platino

A.3.1

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

Efficacy Study of Nivolumab or Chemotherapy in Subjects with Relapsed Small-cell Lung Cancer

Ensayo de eficacia de Nivolumab o quimioterapia en sujetos con cáncer de pulmón microcítico (CPM) en recaída.

A.3.2

Name or abbreviated title of the trial where available

CheckMate 331

A.4.1

Sponsor's protocol code number

CA209-331

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1167-9325

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Bristol-Myers Squibb International Corporation
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Bristol-Myers Squibb International Corporation
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bristol-Myers Squibb International Corporation
B.5.2	Functional name of contact point	GCT-SU
B.5.3	Address:
B.5.3.1	Street Address	Parc de l'Alliance - Avenue de Finlande, 4
B.5.3.2	Town/ city	Braine-l'Alleud
B.5.3.3	Post code	1420
B.5.3.4	Country	Belgium
B.5.4	Telephone number	900 150 160
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-936558-01
D.3.9.3	Other descriptive name	BMS936558
D.3.9.4	EV Substance Code	SUB32944
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	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	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	Topotecan Hospira 4 mg/4 ml concentrate for solution for infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Hospira UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TOPOTECAN
D.3.9.1	CAS number	123948-87-8
D.3.9.4	EV Substance Code	SUB11191MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	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

Relapsed Small Cell Lung Cancer

Cáncer de pulmón microcítico en recaída.

E.1.1.1

Medical condition in easily understood language

Relapsed Small Cell Lung Cancer

Cáncer de pulmón microcítico en recaída.

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	10041068
E.1.2	Term	Small cell lung cancer extensive stage
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	10041069
E.1.2	Term	Small cell lung cancer limited stage
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	10041070
E.1.2	Term	Small cell lung cancer recurrent
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 compare the overall survival (OS) of nivolumab versus chemotherapy in subjects with relapsed SCLC after platinum-based, first-line chemotherapy.

Comparar la Supervivencia Global (SG) de Nivolumab frente a quimioterapia en sujetos con CMP en recaída tras una primera línea de quimioterapia basada en platino.

E.2.2

Secondary objectives of the trial

- To compare the progression free survival (PFS) of nivolumab versus chemotherapy
- To compare the objective response rate (ORR) of nivolumab versus chemotherapy

Compara la supervivencia libre de progresión (SLP) de Nivolumab frente a la quimioterapia
Comparar la tasa de respuestas objetivas (TRO) de Nivolumab frente a la quimioterapia

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 Number 01 - Site Specific, dated 14-May-2015

The objective of this Amendment is 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, CA209331 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 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 específica del sitio, de 14 de mayo 2015 para la obtención de muestras de sangre para estudios de farmacogenética. El objetivo de esta enmienda es permitir la recogida y almacenamiento de muestras de sangre para futuras investigaciones farmacogenéticas exploratorias. BMS utilizará el ADN obtenido de las muestras de sangre y la información de salud recogida del ensayo principal CA209-331 para estudiar la asociación entre variación genética y respuesta al medicamento.BMS, también utilizará el ADN para estudiar las causas y la progresión posterior en de cáncer de pulmón. Las muestras de este ensayo también se usarán junto con otros resultados de investigaciones farmacogenéticas de otros ensayos clínicos para cumplir este objetivo

E.3

Principal inclusion criteria

Adult men and women with histologically or cytologically confirmed SCLC that recurred or progressed after platinum-based, first-line chemotherapy or chemoradiation therapy. Subjects must have had at least 4 cycles of platinum-based, first-line chemotherapy for either limited or extensive stage disease or if less than 4 cycles, must have had a BOR of at least partial or complete response.

Adultos de ambos sexos con CMP confirmado mediante histología o citología que ha recidivado o progresado
después del tratamiento de primera línea con quimioterapia basada en platino o quimiorradioterapia. Los sujetos
deben haber recibido al menos 4 ciclos de quimioterapia de primera línea basada en platino para enfermedad limitada
o extendida o, si han recibido menos de 4 ciclos, tienen que haber presentado una MRG de respuesta parcial o
completa.

E.4

Principal exclusion criteria

Active symptomatic central nervous system metastases, documented carcinomatous meningitis, active, known or suspected autoimmune disease, and prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways), topotecan, or amrubicin.

Metástasis activas y sintomáticas en el sistema nervioso central, meningitis carcinomatosa documentada,
enfermedad autoinmune activa, conocida o sospechada y tratamiento previo con anticuerpos anti-PD-1, anti-PDL1,
anti-PD-L2, anti-CD137, o anti-CTLA-4 (como Ipilimumab o cualquier otro anticuerpo o medicamento dirigido
específicamente a las vías de coestimulación de linfocitos T o los puntos de control inmunitario [checkpoint]),
topotecan o amrubicina.

E.5 End points

E.5.1

Primary end point(s)

Overall survival (OS) in subjects with relapsed SCLC

Supervivencia Global (SG) en sujetos con CPM en recaida

E.5.1.1

Timepoint(s) of evaluation of this end point

Approximately 12 months. Additional survival follow-up may continue for up to 5 years from the completion of the study.

Aproximadamente 12 meses. Un seguimiento adicional de la supervivencia puede continuar hasta 5 años desde que se complete el ensayo.

E.5.2

Secondary end point(s)

1-progression free survival (PFS)
2-objective response rate (ORR)

1- Supevivencia libre de progresión (SLP)
2- Tasa de resouesta objetiva (TRO)

E.5.2.1

Timepoint(s) of evaluation of this end point

Tumor response will be assessed every 6 weeks until Week 30, and every 12 weeks until disease progression or treatment discontinuation.

La respuesta del tumor debe evaluarse cada 6 semanas, hasta la semana 30, y cda 12 semanas hasta la progresión de la enfermedad o la interrupción del 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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Outcomes Research Assessments, Immunogenicity Assessments

Evaluaciones de resultados en salud, y evaluaciones de inmunogenicidad

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

Austria

Belgium

Chile

Czech Republic

Denmark

Finland

France

Germany

Greece

Hungary

Israel

Italy

Japan

Korea, Republic of

Netherlands

Norway

Poland

Romania

Russian Federation

Spain

Switzerland

Taiwan

United Kingdom

United States

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

Last follow-up visit of the last subject

Última visita de seguimiento del último paciente

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:

370

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

370

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

510

F.4.2.2

In the whole clinical trial

740

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 will be eligible to receive BMS supplied study drug. 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

Cuando concluya el EC , los sujetos que sigan demostrando benef. clínico podrán recibir el mto. suministrado por BMS. Este se facilitará mediante una extensión del EC, EC de continuación u otro mecanismo. BMS se reserva el derecho de terminar el acceso al mto. si: a) se rechazase la solicitud de AdC por las AASS responsables; b) dar por terminado el estudio por seguridad; c) el sujeto puede obtener la medicación de un programa estatal o privado; o d) aparecen alternativas terapéuticas locales.

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

2015-10-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-07-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-08-22

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