Clinical Trials Register

Summary
EudraCT Number:	2012-002472-14
Sponsor's Protocol Code Number:	CA209-057
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:	2012-10-02
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

2012-002472-14

A.3

Full title of the trial

An Open-Label Randomized Phase III Trial of BMS-936558 versus Docetaxel in Previously Treated Metastatic Non-squamous Non-small cell Lung Cancer (NSCLC)

Ensayo fase 3, aleatorizado, abierto de BMS-936558 frente a docetaxel en el cáncer de pulmón no microcítico (CPNM) metastásico no epidermoide tratado previamente

A.3.1

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

Study of BMS-936558 compared to Docetaxel in previously treated advanced or metastatic Non-squamous NSCLC

A.4.1

Sponsor's protocol code number

CA209-057

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01673867

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, 8
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.3.2	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	BMS-936558-01
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	Anti-PD-1 Human Monoclonal Antibody; MDX-1106
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	Taxotere 160 mg (20 mg/mL)
D.2.1.1.2	Name of the Marketing Authorisation holder	Aventis Pharma S.A.
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	Taxotere
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	DOCETAXEL
D.3.9.1	CAS number	114977-28-5
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
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

Non-Squamous cell Non-small cell lung cancer

cáncer de pulmón no microcítico metastásico no epidermoide

E.1.1.1

Medical condition in easily understood language

Non-Squamous cell Non-small cell lung cancer

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	10061873
E.1.2	Term	Non-small cell lung 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

E.2 Objective of the trial

E.2.1

Main objective of the trial

The purpose of the study is to compare the overall survival of BMS-936558 as compared with Docetaxel in subjects with non- squamous cell non-small cell lung cancer (NSCLC) after failure of prior platinum-based chemotherapy

Comparar la SG de BMS-936558 frente a docetaxel en sujetos con CPNM no epidermoide después del fracaso de quimioterapia previa basada en platino.

E.2.2

Secondary objectives of the trial

1. To compare the objective response rate of BMS-936558 versus docetaxel
2. To compare the progression-free survival (PFS) of BMS-936558 versus docetaxel
3. To evaluate clinical benefit of BMS-936558 versus docetaxel, in PD-L1 + versus PD-L1- protein expression subgroups
4. To evaluate the proportion of subjects exhibiting disease-related symptom progression, as measured by LCSS, in BMS-936558 and docetaxel groups

Comparar la tasa de respuestas objetivas (TRO) de BMS-936558 con la de docetaxel.
Comparar la supervivencia libre de progresión (SLP) con BMS-936558 frente a docetaxel.
Evaluar el beneficio clínico de BMS-936558 frente a docetaxel, en los subgrupos con expresión de proteína PD-L1+ frente a los sujetos PD-L1-.
Evaluar la proporción de sujetos que muestran progresión de los síntomas relacionados con la enfermedad, medida por la LCSS, en los grupos de BMS-936558 y docetaxel.

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 Protocol Amendment 01, version 1.0, dated 02-Jul-2012

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, CA209057 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 non-squamous NSCLC Samples from this study may also be used in
conjunction with pharmacogenetic research results from other clinical studies to
accomplish this objective.

E.3

Principal inclusion criteria

1) Men & women ? 18 years of age
2) Subjects with histologically or cytologically-documented non-squamous cell NSCLC who present with Stage IIIB/IV disease or recurrent disease following radiation therapy or surgical resection.
3)Disease recurrence or progression during/after one prior platinum-containing chemotherapy regimen for advanced or metastatic disease
4) Measurable disease by CT/MRI per RECIST 1.1 criteria
5) ECOG performance status ? 1
6) An FFPE tumor tissue block or unstained slides of tumor sample (archival or recent) must be available for biomarker evaluation. Specimens must be received by the central lab prior to randomization. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is insufficient

1) Varones y mujeres ? de 18 años y más.
2) Sujetos con CPNM no epidermoide localmente avanzado, documentado histológicamente o citológicamente que presentan enfermedad en estadio IIIB/estadio IV o recurrente después de radioterapia o resección quirúrgica.
3) Los sujetos deben haber experimentado progresión de la enfermedad durante o después de un régimen previo de quimioterapia de combinación que incluya un platino
4) Los sujetos deben tener enfermedad medible mediante TC o RM según los criterios RECIST 1.1.
5) Estado funcional ? 1 del Eastern Cooperative Oncology Group (ECOG)
6) Deben estar disponibles un bloque de tejido tumoral fijado en formol, incluido en parafina o un mínimo de 10 preparaciones no teñidas de muestra tumoral (de archivo o reciente) para la evaluación de biomarcadores, como se describe en la Sección 5.9 que deben haber sido recibidos por los laboratorios centrales para la aleatorización de los sujetos del tratamiento. La biopsia debe ser excisional, incisional o de aguja gruesa. La aspiración con aguja fina es insuficiente.

E.4

Principal exclusion criteria

1) Subjects with active CNS metastases are excluded. Subjects are eligible if CNS metastases are asymptomatic or adequately treated and subjects are neurologically returned to baseline for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ? 10mg daily prednisone (or equivalent)
2) Subjects with carcinomatous meningitis.
3) Subjects with active, known or suspected autoimmune disease, or subjects with interstitial lung disease.
4) Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization.
5) Prior therapy 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).
6) Prior treatment with docetaxel
7) Treatment with any investigational agent within 28 days of first administration of study treatment.

1) sujetos con metástasis activas en el SNC. Los sujetos son elegibles si las metástasis del SNC se tratan adecuadamente y los sujetos han vuelto neurológicamente a la situación basal (excepto los signos o síntomas residuales relacionados con el tratamiento del SNC) durante al menos 2 semanas antes del reclutamiento. Además, los sujetos no deben estar recibiendo corticosteroides o deben estar recibiendo una dosis estable o decreciente de ?10 mg al día de prednisona (o equivalente)
2)Sujetos con meningitis carcinomatosa
3) Sujetos con enfermedad autoinmunitaria activa, conocida o de sospecha o sujetos con antecedentes de enfermedad pulmonar intersticial.
4) Sujetos con un problema que precisa tratamiento sistémico con u otros medicamentos inmunosupresores en el plazo de 14 días antes de la aleatorización.
5) Tratamiento previo con un anticuerpo anti-PD-1, anti-PD-L1, anti-PD-L-2, anti-CD-137 o anti-CTLA-4 (incluido ipilimumab o cualquier otro anticuerpo o fármaco que se dirija específicamente a las vías de coestimulación o control de los linfocitos T)
6) Tratamiento previo con docetaxel
7)Tratamiento con cualquier agente experimental dentro de los 28 días previos a la primera administración del tratamiento del estudio

E.5 End points

E.5.1

Primary end point(s)

Overall Survival

Supervivencia global

E.5.1.1

Timepoint(s) of evaluation of this end point

24 months

24 MESES

E.5.2

Secondary end point(s)

Comparar la tasa de respuestas objetivas (TRO) de BMS-936558 con la de docetaxel
Comparar la supervivencia libre de progresión (SLP) de BMS-936558 con la docetaxel
Evaluar el beneficio clínico de BMS-936558 frente a docetaxel, en los subgrupos con expresión de proteína PD-L1+ frente a los sujetos PD-L1-.
Evaluar la proporción de sujetos que muestran progresión de los síntomas relacionados con la enfermedad, medida por la LCSS, en los grupos de BMS-936558 y docetaxel.

E.5.2.1

Timepoint(s) of evaluation of this end point

24 months

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

Biomarker Assessments: Peripheral Blood and Tumor Markers, Outcomes Research Assessments: Lung Cancer Symptom Scale (LCSS), and EuroPRO Group?s EQ-5D; Immunogenicity Assessments; Healthcare Resource Utilization data

Evaluaciones de biomarcadores : sangre periférica y en muestras tumorales, Evaluaciones de Resultados de Investigación .Escala de Síntomas del Cáncer de Pulmón (Lung Symptom Cancer Scale - LCSS) y EQ-5D del grupo EuroPRO. Las evaluaciones de inmunogenicidad: Se recogerán datos de utilización de recursos sanitarios

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

Argentina

Australia

Austria

Brazil

Canada

Chile

Czech Republic

France

Germany

Hong Kong

Hungary

Italy

Mexico

Peru

Poland

Romania

Russian Federation

Singapore

South Africa

Spain

Switzerland

Turkey

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

The study will end when analysis of survival is complete. All subjects will be followed for overall survival every 3 months until death, lost to follow-up or withdrawal of study consent. The duration of the study will be approximately 2 years (24 months).

El estudio terminará cuando se haya terminado el análisis de la supervivencia.
Todos los sujetos serán seguidos en cuanto a supervivencia global cada 3 meses hasta la muerte, la pérdida para el seguimiento o la retirada del consentimiento del estudio, duración total del estudio será de aproximadamente 2 años (24 meses).

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:

120

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

580

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

290

F.4.2.2

In the whole clinical trial

700

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 the conclusion of the study, subjects who continue to demonstrate clinical benefit will be eligible to receive study drug. Study drug will be provided via an extension of the study, a rollover study requiring approval by responsible health authority and ethics committee, or through another mechanism at the discretion of the sponsor. See also Protocol, section 3.2 for more details.

A la conclusión del estudio, los sujetos que sigan demostrando beneficio clínico serán elegibles para recibir el fármaco del estudio. El fármaco del estudio se facilitará mediante una extensión del estudio, un estudio de continuación que precisa la aprobación por parte de las autoridades sanitarias y el comité de ética o a través de otro mecanismo, a criterio del promotor.Véase también el Protocolo, sección 3.2 para más detalles.

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

2012-11-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-11-05

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

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IMP with orphan designation in the indication
Orphan Designation Number:
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