Clinical Trials Register

Summary
EudraCT Number:	2008-008922-55
Sponsor's Protocol Code Number:	GEIS20
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2009-03-23
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2008-008922-55

A.3

Full title of the trial

ENSAYO FASE II ALEATORIZADO, ABIERTO, MULTICÉNTRICO Y PROSPECTIVO DE DOXORRUBICINA vs TRABECTEDINA Y DOXORRUBICINA EN PRIMERA LÍNEA DE PACIENTES CON SARCOMA DE PARTES BLANDAS AVANZADOS NO OPERABLES Y/O METASTÁSICOS

A.4.1

Sponsor's protocol code number

GEIS20

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Grupo Español de Investigación en Sarcomas
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Yes
D.2.1.1.1	Trade name	YONDELIS 0,25 mg polvo para concentrado para solución para perfusión
D.2.1.1.2	Name of the Marketing Authorisation holder	PHARMA MAR, S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Yondelis
D.3.2	Product code	07417001
D.3.4	Pharmaceutical form
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	TRABECTEDINA
D.3.9.3	Other descriptive name	TRABECTEDINA
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	0.25
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Information not present in EudraCT
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	Doxorrubicina
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Doxorrubicina
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	0.4
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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: 3
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	Information not present in EudraCT
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	Doxorrubicina
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Doxorrubicina
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	0.4
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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

Sarcoma de partes blandas avanzados no operables y/o metastásicos

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9
E.1.2	Level	HLGT
E.1.2	Classification code	10041299
E.1.2	Term	Soft tissue sarcomas

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Determinar la eficacia de la combinación de trabectedina y doxorrubicina en comparación con doxorrubicina sola en pacientes con Sarcomas de Partes Blandas (SPB) avanzados no operables y/o metastásicos

E.2.2

Secondary objectives of the trial

- Determinar la actividad por medio de la respuesta objetiva según RECIST de la combinación trabectedina/ doxorrubicina y del brazo control.
- Determinar la proporción de control tumoral (respuestas más estabilizaciones) en ambas ramas de tratamiento.
- Supervivencia global.
- Determinar la actividad en cambios tisulares extrapolando los criterios de Choi a SPB. (Ver estudio de revisión radiológica asociado)
- Determinar la toxicidad de la combinación trabectedina/ doxorrubicina y del brazo control.
- Determinar expresividad protéica y de RNAm de genes que podrían estar implicados en un perfil de respuesta más favorable o de resistencia respecto a los fármacos objeto de estudio para analizar el impacto pronóstico de los mismos en los parámetros de actividad definidos (Ver estudio traslacional asociado).
- La evaluación de la inestabilidad génica, así como la expresividad proteica que podría condicionar respuesta/resistencia a los fármacos objeto de estudio será correlacionada con varia

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

Subestudio molecular
Se requieren dos tipos de muestras:

1. Tejido fijado e incluido en parafina obtenida al diagnóstico necesario para la revisión histológica, el estudio inmunohistoquímico, de inestabilidad genética y de expresión de mRNA.
2. Sangre periférica, 7 ml de sangre en tubos de EDTA para la obtención de ADN constitutivo para el estudio de inestabilidad génica y polimorfismos.

E.3

Principal inclusion criteria

-El paciente debe firmar voluntariamente el consentimiento informado antes de la realización de cualquier prueba del ensayo que no forme parte de la atención habitual de los pacientes, con el conocimiento por parte del paciente que puede abandonar el ensayo en el momento que quiera, sin que se vea perjudicado en ningún momento su atención posterior.
-Edad superior a 18 años y menor de 70 años.
- Diagnóstico histológico de sarcoma de partes blandas no operables y/o metastásicos.
-Son incluibles los siguientes tipos histológicos:
§ sarcoma pleomórfico indiferenciado (antiguo histiocitoma fibroso maligno)
§ leiomiosarcoma
§ angiosarcoma
§ liposarcoma
§ sarcoma sinovial
§ fibrosarcoma
§ hemangiopericitoma
§ sarcoma neurogénico
§ mixofibrosarcoma
§ sarcoma no clasificable
- Enfermedad medible, de acuerdo con los criterios RECIST.
-Estado funcional 0-2 (ECOG).
-Función medular basal adecuada (hemoglobina > 10 g/dL, leucocitos ≥ 3.000/mm3, neutrófilos ≥ 1.500/mm3, plaquetas ≥ 100.000/mm3). Son aceptables pacientes con alteración de las transaminasas ≤ 2,5 veces los LSN , bilirrubina total ≤ LSN, CPK≤ 2.5 veces los LSN, Fosfatasa alcalina ≤ 2,5 veces más los LSN. (Si la elevación es > 2,5 veces el LSN, entonces la fracción hepática de la fosfatasa alcalina y/o de la 5’ nucleotidasa y/o la GGT deben ser ≤ LSN) , ó cifras de creatinina ≤ 1,6 mg/dL.
-Los pacientes en edad fértil (tanto los varones como las mujeres) deben usar un método eficaz anticonceptivo antes de la entrada en el estudio y durante la realización del estudio. Además, las mujeres deben mantener las medidas anticonceptivas hasta 6 meses después de finalizar el tratamiento mientras que los varones deben prolongar estas medidas hasta 6 meses después del tratamiento. Debe descartarse embarazo mediante prueba de orina (test de embarazo negativo) para la inclusión en el estudio.
-Funcionalidad cardíaca (FEVI) normal, considerando los rangos normales de la institución.

E.4

Principal exclusion criteria

-Pacientes que hayan recibido quimioterapia previamente.
-Pacientes que hayan sido irradiados en la/s única localización/es de enfermedad tumoral medible/s.
-Estado funcional > 2 (ECOG).
-Metástasis en el SNC.
-Cifras de bilirrubina superior al nivel normal.
-Creatinina superior a 1,6 mg/dL.
-Antecedentes de otra enfermedad neoplásica con excepción de basalioma o carcinoma in situ de cérvix adecuadamente tratados.
-Enfermedades cardiovasculares graves (Disnea >= 2 NYHA p.ej.).
-Patologías sistémicas de base que limiten la supervivencia a menos de 2 años, que limiten la disponibilidad del paciente, o que puedan, a juicio clínico, interferir de forma significativa con la toxicidad del tratamiento.
-Enfermedades infecciosas bacterianas, víricas o micóticas no controladas.
-Pacientes embarazadas o lactantes.
-Situaciones psicológicas, familiares, sociológicas o geográficas que no permitan el cumplimiento del protocolo o del consentimiento informado.
-Pacientes que estén actualmente en otro ensayo clínico o recibiendo cualquier agente en investigación.
-Pacientes que hayan participado en un ensayo clínico y/o hayan recibido un agente en investigación en los 30 días anteriores a la inclusión.
-Las siguientes histologías serán excluidas: -Rabdomiosarcoma
-Tumores de la familia de Ewing
-Tumor desmoplásico de célula redonda.
-Sarcoma de células claras
-Sarcoma Alveolar

E.5 End points

E.5.1

Primary end point(s)

SLP: se calculará como el tiempo desde la fecha de aleatorización hasta la fecha de progresión de la enfermedad o muerte (independientemente de la causa de ésta).

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

Yes

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

Information not present in EudraCT

E.7.1.2

Bioequivalence study

Information not present in EudraCT

E.7.1.3

Other

Information not present in EudraCT

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

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.8.3

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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

El ensayo se considerará cerrado desde el punto de vista normativo después de que los datos sobre supervivencia global estén lo suficientemente preparados como para su publicación inicial. Las observaciones de seguimiento de las pacientes incluidas en el ensayo se pueden mantener de forma indefinida.

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

Information not present in EudraCT

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

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

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Varones en Edad Fértil que utilicen medidas anticonceptivas

F.4 Planned number of subjects to be included

F.4.1

In the member state

182

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

2009-06-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-05-14

P. End of Trial
P.	End of Trial Status	Prematurely Ended

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials