Clinical Trials Register

Summary
EudraCT Number:	2016-001645-64
Sponsor's Protocol Code Number:	CA209-714
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:	2016-08-29
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

2016-001645-64

A.3

Full title of the trial

A Double-Blind, Randomized, Two Arm Phase 2 Study of Nivolumab in Combination with Ipilimumab versus Nivolumab in Combination with Ipilimumab Placebo In Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Ensayo de fase 2, doble ciego, aleatorizado, de dos grupos, de Nivolumab en combinación con Ipilimumab frente a Nivolumab en combinación con placebo de Ipilimumab en el carcinoma de células escamosas de cabeza y cuello (CCECC) en recidiva o metastásico

A.3.1

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

Study of Nivolumab in Combination with Ipilimumab compare to nivolumab in combination with Ipilimumab-Placebo in patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Ensayo de Nivolumab en combinación con Ipilimumab frente a Nivolumab en combinación con placebo de Ipilimumab en el carcinoma de células escamosas de cabeza y cuello (CCECC) en recidiva o metastásico

A.3.2

Name or abbreviated title of the trial where available

CheckMate 714

A.4.1

Sponsor's protocol code number

CA209-714

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02823574

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1181-8765

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.5.4	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.3.9.2	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	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.3.9.3	Other descriptive name	BMS734016
D.3.9.4	EV Substance Code	SUB22577
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection/infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Carcinoma de células escamosas de cabeza y cuello (CCECC) en recidiva o metastásico

E.1.1.1

Medical condition in easily understood language

Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Carcinoma de células escamosas de cabeza y cuello (CCECC) en recidiva o metastásico

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	19.0
E.1.2	Level	PT
E.1.2	Classification code	10063569
E.1.2	Term	Metastatic squamous cell carcinoma
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 compare the ORR of the treatment of nivolumab in combination with ipilumumab vs. nivolumab in combination with ipilimumab placebo, as determined by a blinded independent central review (BICR) using Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria, for first line treatment of recurrent or metastatic SCCHN in the platinum refractory setting.

Comparar la TRG del tratamiento de Nivolumab en combinación con Ipilimumab frente a Nivolumab encombinación con placebo de Ipilimumab, determinada mediante una revisión central independiente enmascarada (BRIC) usando los Criterios de Evaluación de la Respuesta en Tumores Sólidos (RECIST 1.1), para el tratamientode primera línea del CCECC recurrente o metastásico en el contexto de refractariedad al platino.

E.2.2

Secondary objectives of the trial

To assess progression-free survival (PFS) all randomized subjects, overall and in, as determined by BICR, of nivolumab in combination with ipilimumab vs. nivolumab in combination with ipilimumab placebo for first line treatment of recurrent or metastatic SCCHN in the platinum eligible and platinum refractory settings, separately and overall.
To assess overall survival (OS) of nivolumab combined with ipilimumab vs. nivolumab in combination with ipilimiumab placebo with for first line treatment of recurrent or metastatic SCCHN in the platinum eligible and platinum refractory settings, separately and overall.
To assess efficacy (ORR, PFS and OS) by PD-L1 expression and HPV p-16 status of nivolumab in combination with ipilumumab compared to nivolumab in combination with ipilimumab placebo for first line treatment of recurrent or metastatic SCCHN in the platinum eligible and platinum refractory settings, separately and overall.

Evaluar SLP en todos los sujetos aleatorizados y según la determinación por el BICR, de Nivolumab en combinación con Ipilimumab frente a Nivolumab en combinación con placebo de Ipilimumab para el tratamiento de 1L del CCECC en recidiva o metastásico en los contextos de elegibilidad para platino y refractariedad al platino, por separado y en conjunto.
Evaluar SG con Nivolumab combinado con Ipilimumab frente a Nivolumab encombinación con placebo de Ipilimumab para el tratamiento de primera línea del CCECC en recidiva ometastásico en los contextos de elegibilidad para platino y refractariedad al platino, por separado y en conjunto.
Evaluar eficacia (TRG, SLP, TRG) según la expresión de PD-L1 y el estado de VPH p-16 de Nivolumab en combinación con Ipilimumab en comparación con Nivolumab en combinación con placebo de Ipilimumab en el tratamiento de 1L del CCECC en recidiva o metastásico en los subgrupos elegibles para platino y refractario al platino, por separado y en conjunto.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Confirmed squamous cell head and neck cancer
Widespread (metastatic) disease, or returned after previous treatment (recurrent)
No previous treatment for metastatic or recurrent disease
Tumor sample must be available for analysis of PDL1 and HPV (oropharynx only)
Performance status (ECOG 0-1)

Pacientes con carcinoma de células escamosas de cabeza y cuello (CCECC) confirmado histológicamente, enfermedad diseminada (metastásica), o que haya recurrido después de tratamiento previo.
Pacienentes sin tratamiento previo para la enfermedad metastásica o en recidiva
Muestra de tumor disponible para la determinación de PD-L1 y HPV ( solamente en orofaringe)
ECOG 0-1

E.4

Principal exclusion criteria

Cancer arising from one of the following primary sites: paranasal sinus, nasopharynx, salivary gland, skin
Any non-squamous subtype
Active autoimmune disease
Positive test for hepatitis B, C or HIV virus
Previous treatment with checkpoint inhibitor drugs
Active CNS metastases or carcinomatous meningitis

Carcinoma de uno de los siguientes sitios priomarios: senos paranasales, nasofaringe, glándula salivar, piel
Cualquier subtupo no escamoso
Enfermedad autoinmune activa
Test positivo para el virus de la hepatitis B, C o VIH
Trtamiento previo con medicamentos inhibidores de puntos de control inmunológicos
Sujetos con metástasis cerebrales activas o meningitis carcinomatosa

E.5 End points

E.5.1

Primary end point(s)

Overall response rate (ORR) in the platinum refractory subgroup , by Blinded Independent Central Review (BICR)

Subjects that are platinum refractory are defined as:
-squamous cell cancer of the head and neck
-recurrence < 6 months after completion of previous platinum based chemotherapy
-no prior therapy for recurrent or metastatic disease

TRG en el subgrupo refractario al platino, determinada mediante una revisión central independiente enmascarada (BRIC).
Los sujetos refraactaarios al platino se definen como:
*cancer de células escamosas de cabeza y cuello
*recurrencia < 6 meses después de completar quimioterapia previa basada en platino
* sin tratamiento previo para enfermedad metastásica o recurrente

E.5.1.1

Timepoint(s) of evaluation of this end point

approximately 19 months

aproximadamente 19 meses

E.5.2

Secondary end point(s)

Overall response rate (ORR) in the platinum eligible subgroup, by Blinded Independent Central Review (BICR)

Subjects that are platinum eligible are defined as:
-squamous cell cancer of the head and neck
-recurrence ≥6 months after completion of previous platinum based chemotherapy
-no prior therapy for recurrent or metastatic disease

Progression Free Survival (PFS) and Overall Survival (OS) in platinum eligible and refractory subgroups

Efficacy (ORR, OS, PFS), by PDL1 and HPV status, in platinum refractory and platinum eligible subgroups

Tasa de Respuesta Global (TRO) en el subgrupo refractario al platino, determinada mediante una revisión central independiente enmascarada (BRIC).
Los sujetos refraactaarios al platino se definen como:
*cancer de células escamosas de cabeza y cuello
*recurrencia < 6 meses después de completar quimioterapia previa basada en platino
* sin tratamiento previo para enfermedad metastásica o recurrente
Supervivencia libre de progresión (SLP) y supervivencia global (SG) en los subgrupos elegibile para platino y refractario al platino.
Eficacia (TRG, SLP y SG) según la expresión de PD-L1 y el estado de VPH p-16 en los subgrupos elegibile para platino y refractario al platino.

E.5.2.1

Timepoint(s) of evaluation of this end point

approximately 19 months

aproximadamente 19 meses

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

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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)

E.8.2.2

Placebo

Yes

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

Belgium

Brazil

Canada

Czech Republic

Finland

France

Ireland

Netherlands

Norway

Romania

Russian Federation

South Africa

Spain

Sweden

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

LVLS

Última visita del último paciente (LPLV)

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:

316

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

135

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

116

F.4.2.2

In the whole clinical trial

451

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 BMS supplied study drug up to 12 months after the approval of investigational product by the responsible health authority or until the investigational product becomes commercially available within the country, whichever occurs sooner.

Please refer to Section 3.3 of the Protocol for further details.

Cuando concluya el EC, los sujetos que sigan demostrando beneficio clínico serán elegibles para recibir el medicamento suiministradio por BMS hasta 12 meses después de la aprobación del medicamento por una agencia reguladiora o hasta que esté comercialmrente disponible en algín pais , lo que ocurra primero.
Para más detalles consultar la sección 3.3 del protocolo.

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

2016-10-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-09-19

P. End of Trial
P.	End of Trial Status	Completed

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