Clinical Trials Register

Summary
EudraCT Number:	2008-006831-10
Sponsor's Protocol Code Number:	1199.15
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:	2010-05-27
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

2008-006831-10

A.3

Full title of the trial

Estudio de fase III, multicéntrico, aleatorizado y doble ciego para evaluar la eficacia y seguridad de BIBF 1120 en combinación con carboplatino y paclitaxel comparado con placebo en combinación con carboplatino y paclitaxel en pacientes con cáncer de ovario avanzado.

Multicenter, randomised, double-blind Phase III trial to investigate the efficacy and safety of BIBF 1120 in combination with carboplatin and paclitaxel compared to placebo plus carboplatin and paclitaxel in patients with advanced ovarian cancer

A.3.2

Name or abbreviated title of the trial where available

BIBF 1120 or placebo in combination with standard chemotherapy in advanced ovarian cancer

A.4.1

Sponsor's protocol code number

1199.15

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	Boehringer Ingelheim España, S.A.
B.1.3.4	Country	Spain
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
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	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	BIBF 1120
D.3.4	Pharmaceutical form	Capsule, soft
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	BIBF 1120
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	100
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	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	BIBF 1120
D.3.4	Pharmaceutical form	Capsule, soft
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	BIBF 1120
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.3.11 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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, soft
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, soft
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Cáncer de ovario avanzado, cáncer de trompas de Falopio o cáncer peritoneal primario

Advanced ovarian cancer, fallopian tube cancer or primary peritoneal cancer

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10033128
E.1.2	Term	Ovarian cancer

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10016180
E.1.2	Term	Fallopian tube cancer

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10026469
E.1.2	Term	Malignant neoplasm of specified parts of peritoneum

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10026340
E.1.2	Term	Malignant neoplasm of peritoneum, unspecified

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Investigar la eficacia y seguridad de BIBF 1120 en combinación con quimioterapia frente a placebo en combinación con quimioterapia en pacientes con cáncer de ovario avanzado

To evaluate whether BIBF 1120 in combination with standard therapy of paclitaxel and carboplatin in patients with advanced ovarian cancer, fallopian tube cancer or primary peritoneal cancer is more effective than placebo in combination with standard therapy of paclitaxel and carboplatin.

supervivencia sin progresión

Primary endpoint: progression-free survival

E.2.2

Secondary objectives of the trial

progression free survival according to modified RECIST-1.1 (key secondary endpoint)
overall survival
time to tumour marker progression
objective response in a subgroup of patients

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

La farmacogenética investiga las variaciones genéticas para tratar de explicar las diferentes
respuestas de los pacientes a los fármacos.

E.3

Principal inclusion criteria

(1) primer diagnóstico confirmado histológicamente de cáncer epitelial de ovario, trompas de Falopio o cáncer peritoneal primario (véase el apartado 10.2.1)
(2) estadios FIGO IIB – IV
(3) mujeres de 18 años de edad o mayores
(4) esperanza de vida de 6 meses como mínimo
(5) estado funcional de 0, 1 ó 2 en la escala del Eastern Cooperative Oncology Group (ECOG)
(6) cirugía previa, definida como:
(a) reducción quirúrgica para conseguir la máxima citorreducción con el objetivo de no dejar tumor residual o
(b) biopsia o cirugía limitada en pacientes con la enfermedad en estadio IV para las que la citorreducción no se considera adecuada, si:
• el diagnóstico se confirma histológicamente y
• no está prevista una intervención quirúrgica antes de la progresión de la enfermedad (que incluye el intervalo de la citorreducción quirúrgica)
(7) la paciente ha otorgado el consentimiento informado por escrito conforme a las normas de la Buena Práctica Clínica de la Conferencia Internacional de Armonización (ICH-BPC) y a la normativa local
(8) aplicación programada de la primera dosis de quimioterapia tras la cicatrización de la herida pero como máximo a las 10 semanas después de la intervención

E.4

Principal exclusion criteria

(1) diagnóstico histológico de un tumor benigno o limítrofe (“tumor de bajo potencial maligno”) o de un tumor maligno de origen no epitelial (p. ej., tumor de células germinales, tumor del estroma de los cordones sexuales) de ovario, trompas de Falopio o del peritoneo (véase el apartado 10.2.2)
(2) intervención quirúrgica programada en las 124 semanas después de la aleatorización en este estudio, incluido el intervalo de la citorreducción quirúrgica
(3) herida no cicatrizada clínicamente relevante, úlcera (del tracto intestinal o cutánea) o fractura ósea
(4) síntomas clínicos o signos de obstrucción intestinal que requieran nutrición o hidratación parenteral
(5) síntomas clínicos de metástasis cerebrales o diagnóstico por imagen de metástasis cerebral
(6) neuropatía sensorial o motora preexistente CTCAE  2, excepto por traumatismo
(7) antecedentes de episodios tromboembólicos mayores, definidos como:
(a) embolia pulmonar (EmP) en los 6 meses antes de la inclusión en el estudio
(b) embolia pulmonar recurrente (antecedentes de 2 episodios como mínimo)
(c) antecedentes de al menos 2 episodios no provocados (= sin un factor de riesgo transitorio o reversible) de trombosis venosa profunda proximal
(d) antecedentes de un episodio provocado (= con un factor de riesgo transitorio o reversible, como una intervención quirúrgica) de trombosis venosa profunda proximal o de vasos viscerales en los 6 meses antes de la inclusión sin anticoagulación terapéutica estable
(8) trombosis o episodio tromboembólico anterior en presencia de una coagulopatía heredada (inclusive deficiencia de antitrombina, deficiencia de proteína C o proteína S, mutación del Factor V de Leiden, mutación G20210A en el gen de la protrombina)
(9) trastorno hemorrágico conocido, heredado o adquirido
(10) enfermedades cardiovasculares significativas, como:
(a) hipertensión no controlada por tratamiento médico,
(b) angina de pecho inestable en los últimos 6 meses,
(c) antecedentes de infarto de miocardio en los últimos 6 meses,
(d) insuficiencia cardiaca congestiva con clasificación funcional de grado > II de la New York Heart Association (NYHA),
(e) arritmia cardiaca clínicamente relevante
(f) enfermedad vascular periférica en estadio  3 de Fontaine
(11) derrame pericárdico clínicamente relevante (p. ej., derrame pericárdico con signos ecocardiográficos o clínicos de deterioro hemodinámico),
(12) antecedentes de un accidente cerebrovascular, accidente isquémico transitorio o hemorragia subaracnoidea en los últimos 6 meses
(13) valores analíticos que indiquen un aumento de riesgo de los acontecimientos adversos:
(a) filtración glomerular < 40 ml/min (son suficientes las estimaciones según la fórmula de Cockroft-Gault)
(b) recuento absoluto de neutrófilos (RAN) < 1500 neutrófilos/µl
(c) RAN  1500/µl solo con inducción o soporte de los factores estimulador de colonias de granulocitos
(d) recuento de plaquetas < 100 000/µl
(e) hemoglobina < 9,0 g/dl
(f) proteinuria CTCAE 2 o superior
(g) bilirrubina total por encima del límite superior de la normalidad
(h) concentración de ALAT o ASAT > 2,5 x límite superior de la normalidad
(i) tiempo de protrombina o tiempo de tromboplastina parcial: desviación superior al 50% de los límites normales en ausencia de anticoagulación terapéutica
(14) infecciones graves, especialmente las que requieran tratamiento antibiótico por vía sistémica (antimicrobianos, antifúngicos) o tratamiento antivírico, inclusive por
(a) infección por el virus de la hepatitis B y/o C
(b) infección por el VIH
(15) diabetes mellitus mal controlada u otra contraindicación al tratamiento con altas dosis de corticoesteroides
(16) trastornos gastrointestinales o alteraciones que podrían afectar a la absorción del fármaco en estudio
(17) otras neoplasias diagnosticadas en los últimos 5 años, con excepción de las siguientes:
(a) cáncer de piel no melanomatoso (tratado adecuadamente)
(b) carcinoma cervical in situ (tratado adecuadamente)
(c) carcinoma de mama in situ (tratado adecuadamente)
(d) cáncer endometrial previo o sincrónico (tratado adecuadamente), siempre que se cumplan los siguientes criterios:
• estadio FIGO  IB de la enfermedad (tumor invade menos de la mitad del miometrio)
• no está poco diferenciado (menor que grado 3, sin clasificación histológica como cáncer seroso papilar o de células claras)
(18) tratamiento sistémico previo para el cáncer de ovario (p. ej., quimioterapia, tratamiento con anticuerpos monoclonales, tratamiento oral dirigido, tratamiento hormonal)
(19) tratamiento citotóxico sistémico anterior
(20) tratamiento previo con BIBF 1120 o con cualquier otro inhibidor de la angiogenesis
(21) radioterapia previa
(a) al abdomen o
(b) a un volumen blanco extra-abdominal que conlleve un riesgo de toxicidad adicional a la quimioterapia
(22)analítica que pueda aumentar el riesgo asociado a la participación en el estudio o a la administración del fárma

E.5 End points

E.5.1

Primary end point(s)

supervivencia sin progresión
progression free survival

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

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

Yes

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)

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

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.8.3

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

300

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

Information not present in EudraCT

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

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 estudio clínico se dará por concluido tan pronto como la última paciente haya fallecido o haya sido perdida en el seguimiento o en el momento del análisis final como máximo. El análisis final se realizará 60 meses después de que la última paciente fuera incluida en el estudio.
The clinical trial will be considered completed as soon as the last patient has died or was lost to follow-up or at the time of the final analysis at the latest. The final analysis will be performed 60 months after the

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	No
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	No
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	30
F.4.2	For a multinational trial
F.4.2.1	In the EEA	1200
F.4.2.2	In the whole clinical trial	1300

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

2010-07-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-07-09

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-09-15

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