Clinical Trials Register

Summary
EudraCT Number:	2012-003173-25
Sponsor's Protocol Code Number:	ACOG-1201
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

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

2012-003173-25

A.3

Full title of the trial

Clinica trial PHASE I-II of LEDC (Liposomal Encapsulated Doxorubicin Cytrate,
Myocet®) + CARBOPLATIN IN EPITHELIAL ginecological CANCER

Estudio Fase I-II multicéntrico, abierto, de la combinación de doxorrubicina liposomal encapsulada (Myocet®) y carboplatino en el tratamiento de pacientes con cáncer ginecológico o peritoneal primario recurrente

A.3.1

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

Clinica trial of LEDC (Liposomal Encapsulated Doxorubicin Cytrate,
Myocet®) + CARBOPLATIN IN EPITHELIAL ginecological CANCER

A.4.1

Sponsor's protocol code number

ACOG-1201

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	Dr. Andrés Poveda Velasco
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	Lavoratorios TEVA
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Dynamic Science
B.5.2	Functional name of contact point	Angel Pérez
B.5.3	Address:
B.5.3.1	Street Address	c/azcona 31
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28028
B.5.3.4	Country	Spain
B.5.4	Telephone number	000003491 456 11 05000
B.5.5	Fax number	000003491 456 11 260000
B.5.6	E-mail	a.perez@dynasolutions.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	Yes
D.2.1.1.1	Trade name	MYOCET 50 MG POLVO Y PREMEZCLAS CONCENTRADO PARA DISPERSION LIPOSOMICA PARA PERFUSION
D.2.1.1.2	Name of the Marketing Authorisation holder	Cephalon Europe
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.3.4	Pharmaceutical form	Concentrate for dispersion 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	Myocet
D.3.9.3	Other descriptive name	Doxorrubicina liposomal encapsulada
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	40 to 70
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.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	Yes
D.2.1.1.1	Trade name	CARBOPLATINO TEVA 10 mg/ml CONCENTRADO PARA SOLUCION PARA PERFUSION
D.2.1.1.2	Name of the Marketing Authorisation holder	TEVA GENERICOS ESPAÑOLA, S.L.
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	Carboplatino
D.3.2	Product code	65108
D.3.4	Pharmaceutical form	Concentrate and solvent 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	Carboplatino
D.3.9.3	Other descriptive name	Carboplatino
D.3.10	Strength
D.3.10.1	Concentration unit	ml millilitre(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	AUC5 to AUC5
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

gynecological cancer

cancer ginecológico

E.1.1.1

Medical condition in easily understood language

gynecological cancer

cancer ginecológico

E.1.1.2

Therapeutic area

Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Phase I (Dose escalation)
To determine the maximum-tolerated dose (MTD) and recommended phase II dose of
the combination of Carboplatin + Myocet every three weeks
Phase II (Expansion)
To evaluate the activity (objective responses) of the combination of
Carboplatin+Myocet every 3weeks in patients with PS and PPS relapse.

? Fase I de escalado de dosis: Definir la dosis máxima tolerada (DMT) de la combinación de Myocet® y carboplatino en pacientes con cáncer ginecológico (de cérvix, de endometrio, de trompas o de ovario) o peritoneal primario recurrente.
? Fase II de expansión: Evaluar la actividad de la dosis recomendada de la combinación de Myocet® y carboplatino definida en la fase I, en términos de tasa de respuesta global, definida como respuesta parcial y completa según los criterios RECIST v1.1, en pacientes con una primera, segunda o tercera recidiva platino-sensible o parcialmente platino-sensible de cáncer epitelial de ovario, cáncer tubárico o peritoneal primario.

E.2.2

Secondary objectives of the trial

To assess the toxicity of the combination Myocet+Carboplatin in PPS EOC patients.
To evaluate Pharmacokinetics
To assess PFS and OS

Determinar la supervivencia libre de progresión (SLP) y la supervivencia global (SG).
Evaluar la toxicidad de este régimen de combinación según los criterios de toxicidad estándar (NCI-CTCAE v4.03) (véase Anexo 11).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients will participate in the clinical trial must meet each of the criteria described below:? Patients who have voluntarily signed informed consent before performing any test trial that is not part of routine care of patients.? Patients who do not have any condition (medical, social or psychological) that prevents compliance with the schedule of study visits and appropriate follow-up in the study.? Female patients aged less than 18 years.o Phase I:- Patients with ovarian cancer, endometrial, cervical, tubal or primary peritoneal.- Patients in progression and recurrence at least 2 treatment lines, and no active treatment option.or Phase II:- Patients with first, second or third recurrence of epithelial ovarian carcinoma or primary peritoneal tubal- Patients who have received a platinum-based regimen in the previous line of treatment before inclusion in the study.- Patients with relapsed platinum-sensitive (more than 12 months after the last administration of platinum) or- Patients with relapsing-partially platinum-sensitive (6-12 months after the last administration of platinum).? measurable disease according to the Criteria for Response Assessment in Solid Tumors (RECIST v1.1) confirmed clinically or radiologically, or non-measurable evaluable disease.? Prior radiation therapy for ? 25% of the hematopoietic system, at least 6 weeks before inclusion in the study.? Hormone interrupted during the 10 days prior to inclusion in the study.? Immunotherapy discontinued at least 4 weeks before inclusion in the study? ECOG Performance status ? 2.? Life expectancy ? 3 months.? Platelet count ? 100,000 ³? Hemoglobin ? 10 g / dl.? neutrophil count ? 1.5 x 10 ³ / mm ³.? Serum creatinine <1.5 times the upper limit of normal (ULN).? Bilirubin <1.5 times ULN.? AST / ALT <2.5 times ULN.? ejection fraction (LVEF) ? 50% measured by echocardiography or MUGA.? negative pregnancy test.

Los pacientes que vayan a participar en el ensayo clínico deben cumplir cada uno de los criterios descritos a continuación:
? Pacientes que hayan firmado voluntariamente el consentimiento informado antes de la realización de cualquier prueba del ensayo que no forme parte de la atención habitual de los pacientes.
? Pacientes que no tengan ninguna condición (médica, social o psicológica) que le impida cumplir con el calendario de visitas del estudio y con un adecuado seguimiento en el estudio.
? Pacientes mujeres con edad igual o superior a 18 años.
o Fase I:
- Pacientes con cáncer ovárico, endometrial, cervical, de trompas o peritoneal primario.
- Pacientes en progresión y recurrencia al menos a 2 líneas de tratamiento, y sin tratamiento activo opcional.
o Fase II:
- Pacientes con primera, segunda o tercera recidiva de carcinoma epitelial de ovario tubárico o peritoneal primario
- Pacientes que hayan recibido un régimen basado en platino en la línea anterior de tratamiento previa inclusión en el estudio.
- Pacientes en recaída platino-sensible (más de 12 meses tras la última administración de platino) o
- Pacientes en recaída parcialmente-platino-sensible (entre 6-12 meses tras la última administración de platino).
? Enfermedad medible de acuerdo a los Criterios para la Evaluación de la Respuesta en Tumores Sólidos (RECIST v1.1), confirmada clínica o radiológicamente, o enfermedad evaluable no medible.
? Radioterapia previa sobre ?25% del sistema hematopoyético, al menos en las 6 semanas previas a la inclusión en el estudio.
? Hormonoterapia interrumpida durante los 10 días anteriores a la inclusión en el estudio.
? Inmunoterapia interrumpida al menos 4 semanas antes de la inclusión en el estudio
? Estado funcional ECOG?2.
? Esperanza de vida ? 3 meses.
? Recuento de plaquetas ? 100.000/mm³
? Hemoglobina ? 10 g/dl.
? Recuento de neutrófilos ? 1,5 x 10³/mm³.
? Creatinina sérica < 1,5 veces el límite superior de la normalidad (LSN).
? Bilirrubina < 1,5 veces LSN.
? AST/ALT < 2,5 veces LSN.
? Fracción de eyección del ventrículo izquierdo (FEVI) ?50% medido por ecocardiografía o MUGA.
? Prueba de embarazo negativa.

E.4

Principal exclusion criteria

Therapy prior pegylated liposomal doxorubicin or other anthracyclines. (Phase II).
? It supports previous anthracycline treatment if no response (Phase I).
? Known hypersensitivity to any of the study drugs.
? Evidence of other disease, metabolic dysfunction, physical examination finding or findings on clinical laboratory tests that create a reasonable suspicion that there is a condition or illness that precludes the use of any investigational drugs or put the patient in a high risk of treatment complications.
? Patients who are currently in another clinical trial or receiving any investigational agent within 30 days prior to their inclusion.
? History of other active neoplastic disease over the past 5 years.
? History of heart disease
? Active infection or other clinically severe infection.

? Terapia previa con doxorrubicina liposomal pegilada u otras antraciclinas. (Fase II).
? Se admite tratamiento previo con antraciclinas si hubo respuesta (Fase I).
? Hipersensibilidad conocida a cualquiera de los fármacos de estudio.
? Evidencia de otra enfermedad, disfunción metabólica, hallazgo en el examen físico o hallazgo en las pruebas de laboratorio clínico que originen una sospecha razonable de que exista una condición o enfermedad que contraindique el uso de alguno de los fármacos en investigación o ponga al paciente en un riesgo elevado de complicaciones del tratamiento.
? Pacientes que estén actualmente en otro ensayo clínico o recibiendo cualquier agente en investigación en los 30 días previos a su inclusión.
? Historia de otra enfermedad neoplásica activa en los últimos 5 años.
? Antecedentes de enfermedad cardiaca
? Infección activa u otra infección clínicamente severa.

E.5 End points

E.5.1

Primary end point(s)

Incidence rate of DLT (First cycle) at every dose level (phase I)
? Objective response rate (ORR) according to RECIST 1.1 (phase II)

? Incidencia de DLT (primer ciclo) en cada nivel de dosis (Fase 1)
? Respuestas Objetivas (ORR) según criterios RECIST (Fase 2)

E.5.1.1

Timepoint(s) of evaluation of this end point

Incidence rate of DLT (First cycle) at every dose level (phase I)
? Objective response rate (ORR) according to RECIST 1.1 (phase II)

? Incidencia de DLT (primer ciclo) en cada nivel de dosis (Fase 1)
? Respuestas Objetivas (ORR) según criterios RECIST (Fase 2)

E.5.2

Secondary end point(s)

To assess the security of the combination: type of adverse events, frequency,
grade according to CTC v4.0.
? To evaluate the pharmacokinetics: plasma concentration of Carboplatin in
combination with Myocet and basic PK data.

? Seguridad: tipo, frecuencia y grado de reacciones adversas segun escala CTC v4.0
? Farmacocinética: concentración plasmática de Carboplatino en combinación con Myocet y parámetros básicos de PK.
? PFS y OS según RECIST.

E.5.2.1

Timepoint(s) of evaluation of this end point

Seguridad: tipo, frecuencia y grado de reacciones adversas segun escala CTC v4.0
? Farmacocinética: concentración plasmática de Carboplatino en combinación con Myocet y parámetros básicos de PK.
? PFS y OS según RECIST.

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

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)

Yes

E.7.1.1

First administration to humans

Yes

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

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

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

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

The study will end when all patients progress or drop out prematurely

el estudio finalizará cuando todos los pacientes progresen o abandonen de forma prematura

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:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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.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)

Once completed the study, patients will be treated clinical practice following their centers

Una vez finalice el estudio las pacientes serán tratadas siguiendo la práctica clínica habitual de sus centros

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

2012-12-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-10-16

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

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