Clinical Trials Register

Summary
EudraCT Number:	2011-000509-29
Sponsor's Protocol Code Number:	BO25734/TDM4997g
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:	2012-03-16
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

2011-000509-29

A.3

Full title of the trial

A Phase III randomized, multicenter, two-arm, open-label trial to evaluate the efficacy of T-DM1 compared with treatment of physician?s choice in patients with HER2-positive metastatic breast cancer who have received at least two prior regimens of HER2-directed therapy.

Ensayo de fase III, aleatorizado, multicéntrico, de dos grupos, abierto, para evaluar la eficacia de T DM1 en comparación con el tratamiento de elección en pacientes con cáncer de mama metastásico HER2-positivo que han recibido como mínimo dos pautas previas de tratamiento dirigido contra HER2.

A.3.1

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

An Open-Label Study of trastuzumab emtansine (T-DM1) compared to physician's choice in patients with HER2-Positive Metastatic Breast Cancer.

Estudio abierto de trastuzumab emtansine (T-DM1) comparado con el tratamiento de elección en pacientes con Cáncer de Mama metastásico HER-2 positivo.

A.4.1

Sponsor's protocol code number

BO25734/TDM4997g

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00000000

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	F. Hoffmann-La Roche Ltd
B.1.3.4	Country	Switzerland
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	F. Hoffmann-La Roche Ltd
B.4.2	Country	Switzerland
B.4.1	Name of organisation providing support	Genentech Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	F. Hoffmann-La Roche Ltd
B.5.2	Functional name of contact point	Trial Information Support Line-TISL
B.5.3	Address:
B.5.3.1	Street Address	Grenzacherstrasse 124
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4070
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	NANANANA
B.5.5	Fax number	NANANANA
B.5.6	E-mail	global.rochegenentechtrials@roche.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	trastuzumab emtansine (T-DM1)
D.3.2	Product code	RO530-4020/F02-01
D.3.4	Pharmaceutical form	Powder for 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	trastuzumab emtansine (T-DM1)
D.3.9.1	CAS number	1018448-65-1
D.3.9.2	Current sponsor code	RO5304020
D.3.9.3	Other descriptive name	T-DM1, Trastuzumab-MCC-DM1
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	160
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	Yes
D.3.11.13.1	Other medicinal product type	Antibody-drug conjugate comprised of a humanized monoclonal antibody (trastuzumab) and DM1 Anticuerpo conjugado conteniendo un anticuerpo monoclonal humanizado (trastuzumab) y DM1
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.2.5	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	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	DOCETAXEL
D.3.9.1	CAS number	114977-28-5
D.3.9.2	Current sponsor code	na
D.3.9.3	Other descriptive name	na
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	10
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PACLITAXEL
D.3.9.1	CAS number	33069-62-4
D.3.9.2	Current sponsor code	na
D.3.9.3	Other descriptive name	na
D.3.9.4	EV Substance Code	SUB09583MIG
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CAPECITABINE
D.3.9.1	CAS number	154361-50-9
D.3.9.2	Current sponsor code	na
D.3.9.3	Other descriptive name	na
D.3.9.4	EV Substance Code	SUB12474MIG
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	150
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TRASTUZUMAB
D.3.9.1	CAS number	180288-69-1
D.3.9.2	Current sponsor code	na
D.3.9.3	Other descriptive name	na
D.3.9.4	EV Substance Code	SUB12612MIG
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	150
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LAPATINIB
D.3.9.1	CAS number	231277-92-2
D.3.9.2	Current sponsor code	na
D.3.9.3	Other descriptive name	na
D.3.9.4	EV Substance Code	SUB25379
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	250
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	VINORELBINE
D.3.9.1	CAS number	71486-22-1
D.3.9.2	Current sponsor code	na
D.3.9.3	Other descriptive name	na
D.3.9.4	EV Substance Code	SUB00069MIG
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	GEMCITABINE
D.3.9.1	CAS number	95058-81-4
D.3.9.2	Current sponsor code	na
D.3.9.3	Other descriptive name	na
D.3.9.4	EV Substance Code	SUB07892MIG
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	200
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	Yes
D.3.11.13.1	Other medicinal product type	antineoplastic agents; see section 3.6 of the study protocol Agentes antineoplásicos; ver sección 3,6 del protocolo del estudio

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

Cáncer de Mama Metastásico HER2 positivo (CMM)

E.1.1.1

Medical condition in easily understood language

Cáncer de Mama Metastásico HER2 positivo

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	LLT
E.1.2	Classification code	10027475
E.1.2	Term	Metastatic 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	10065430
E.1.2	Term	HER-2 positive breast 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

- Objective response rate by independent review
- Overall survival (OS)

- Tasa de respuestas objetivas basada en una revisión independiente
- Supervivencia global (SG)

E.2.2

Secondary objectives of the trial

- To evaluate the objective response rate (ORR) by investigator assessment.
- To evaluate the progression-free survival, duration of response, clinical benefit rate, and landmark survival rate (6-month survival rate and 1-year survival rate) of T-DM1 compared with treatment of physician?s choice.
-To evaluate the safety of T-DM1 compared with treatment of physician?s choice.

- Evaluar la tasa de respuestas objetivas (TRO) según la evaluación del investigador.
- Evaluar la supervivencia libre de progresión, la duración de la respuesta, la tasa de beneficio clínico y la tasa de supervivencia en los puntos de referencia (tasa de supervivencia a 6 meses y a un año) de T DM1 en comparación con el tratamiento de elección.
- Evaluar la seguridad de T DM1 en comparación con el tratamiento de elección.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Edad ? 18 años.
- Cáncer de mama documentado mediante histología o citología
- Cáncer de mama metastásico o localmente avanzado/recurrente irresecable
- Enfermedad HER2-positiva, confirmada prospectivamente por el laboratorio central
- Progresión de la enfermedad durante el último tratamiento recibido, según la definición del investigador
- Tratamiento previo con una antraciclina, trastuzumab, un taxano, lapatinib y capecitabina
- Progresión de la enfermedad después de dos pautas como mínimo de tratamiento dirigido contra HER2 en caso de enfermedad metastásica o localmente avanzada/recurrente irresecable
- Tratamiento previo con trastuzumab durante 6 semanas como mínimo para la enfermedad metastásica o localmente avanzada/recurrente irresecable.
- Los pacientes deberán haber tenido al menos 6 semanas de exposición previa a lapatinib y capecitabina

E.4

Principal exclusion criteria

- Quimioterapia ? 21 días antes del primer tratamiento del estudio
- Trastuzumab ? 21 días antes del primer tratamiento del estudio
- Lapatinib ? 14 días antes del primer tratamiento del estudio
- Participación previa en un estudio con T DM1, independientemente de si el paciente recibió anteriormente T DM1
- Metástasis cerebrales no tratadas o sintomáticas, o que precisan radioterapia, cirugía o tratamiento esteroideo para controlar los síntomas en los 2 meses anteriores a la aleatorización

E.5 End points

E.5.1

Primary end point(s)

- Tasa de respuestas objetivas basada en una revisión independiente
- Supervivencia global (SG)

E.5.1.1

Timepoint(s) of evaluation of this end point

Final analysis of OS will take place about 36 months after FPI.

El análisis final de la SG se realizará 36 meses antes de FPI

E.5.2

Secondary end point(s)

- Tasa de respuestas objetivas (TRO) según la evaluación del investigador
- Supervivencia libre de progresión (SLP)
- Duración de la respuesta objetiva
- Tasa de beneficio clínico
- Tasa de supervivencia en los puntos de referencia

E.5.2.1

Timepoint(s) of evaluation of this end point

Secondary Analysis will take place when 489 patients enrolled and followed for 9 months i.e. about 30 months from FPI.

El análisis secundario se realizará cuando se hayan incluido 489 pacientes y se haya realizado el seguimiento durante 9 meses, es decir, alrededor de 30 meses desde FPI

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

Yes

E.6.13.1

Other scope of the trial description

Overall survival (OS); progression-free survival, duration of response, clinical benefit rate

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

Brazil

Canada

Czech Republic

France

Germany

Hungary

India

Israel

Italy

Korea, Republic of

Norway

Poland

Russian Federation

Slovakia

Spain

Sweden

Switzerland

Thailand

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

- La fecha de corte de los datos para el análisis principal de la Tasa de Respuesta Objetiva (TRO) será aproximadamente 9 meses después de la inclusión de unos 489 pacientes con enfermedad mensurable en el momento basal (según la determinación del CRI).

- El punto de corte para el análisis final de la SG será cuando se hayan producido alrededor de 496 muertes. El estudio se cerrará tras el análisis final de la SG.

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:

795

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

400

F.4.2.2

In the whole clinical trial

795

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)

Genentech / Roche evaluará la conveniencia de continuar ofreciendo T-DM1 para los pacientes del estudio después de la evaluación de los resultados primarios de eficacia y de datos de seguridad recogidos en el estudio. Los pacientes que experimentan beneficios al final del estudio pueden ser tratados en un estudio de extensión.

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

2011-10-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-10-06

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-08-31

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