Clinical Trials Register

Summary
EudraCT Number:	2006-003147-23
Sponsor's Protocol Code Number:	IMCL CP11-0602
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:	2007-03-23
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

2006-003147-23

A.3

Full title of the trial

Estudio de Fase 2 abierto, multicentrico para evaluar la eficacia y tolerancia del IMC-11F8 en combinación con 5-FU/FA y Oxaliplatino (Folfox-6 modificado) en paciente con un cáncer colorectal no tratado, localmente avanzado o metastasico

A.4.1

Sponsor's protocol code number

IMCL CP11-0602

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	ImClone Systems Incorporated
B.1.3.4	Country	United States
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	IMC-11F8
D.3.4	Pharmaceutical form	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.3.11 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)	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)	Yes
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	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	Oxaliplatino
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	OXALIPLATIN
D.3.9.1	CAS number	61825943
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	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	Yes
D.3.11.13.1	Other medicinal product type	Citostaticos
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	Folinato Calcico
D.3.4	Pharmaceutical form	Powder 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	CALCIUM FOLINATE
D.3.9.1	CAS number	1492188
D.3.9.3	Other descriptive name	Leucovorina (sal calcica)
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	350
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	Yes
D.3.11.13.1	Other medicinal product type	Desintoxicante de Citostaticos
D.IMP: 4
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	Fluorouracilo
D.3.4	Pharmaceutical form	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	FLUOROURACIL
D.3.9.1	CAS number	51218
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	50
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	Yes
D.3.11.13.1	Other medicinal product type	Citostaticos

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

Cancer de colon localmente avanzado y/o metastasico

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	10052362
E.1.2	Term	Metastatic colorectal 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	10010035
E.1.2	Term	Colorectal cancer stage IV

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	10010034
E.1.2	Term	Colorectal cancer stage III

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

El objetivo principal de este estudio es evaluar la actividad antitumoral (mejor tasa de respuesta global) del anticuerpo monoclonal IMC-11F8 anti-EGFR, administrado en combinación con el régimen de quimioterapia FOLFOX-6 modificado en pacientes con cáncer colorrectal no tratado, localmente avanzado o metastásico.

E.2.2

Secondary objectives of the trial

Los objetivos secundarios son evaluar la combinación IMC-11F8/FOLFOX-6 modificado para:
• la supervivencia global (SG)
• la supervivencia sin progresión (SSP)
• el perfil de tolerancia
• la duración de la respuesta
• el perfil farmacocinético y la inmunogenia del IMC-11F8

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. El paciente debe tener cáncer colorrectal histológicamente demostrado, con EGFR detectable o no detectable. Los pacientes que no dispongan de tejido suficiente para la prueba de EGFR se someterán a biopsia de un tumor accesible. Se ofrecerá un formulario de renuncia a los pacientes que no deseen someterse a una biopsia.
2. El paciente tiene adenocarcinoma de colon o recto localmente avanzada no extirpable o metastásico.
3. El paciente tiene al menos una lesión diana mesurable en una dimensión (≥ 2 cm con técnicas convencionales ≥1 cm con tomografía computarizada espiral [TC]) mediante TC o RM; La(s) lesión(es) diana no debe hallarse dentro de un área irradiada.
4. El paciente tiene una edad ≥ 18 años.
5. El paciente tiene una esperanza de vida de ≥6 meses.
6. El paciente tiene un estado funcional (EF) ECOG (Eastern Cooperative Oncology Group) ≤ 2 en el momento de la inclusión en el estudio.
7. El paciente tiene una función hematológica adecuada, según se demuestra mediante un recuento absoluto de neutrófilos (RAN) ≥1,5 x 109/l, hemoglobina ≥10 g/dl (el paciente puede estar recibiendo transfusiones o estar recibiendo eritropoyetina para cumplir con este criterio), y plaquetas ≥100 x 109/l.
8. El paciente tiene una función hepática adecuada definida como una bilirrubina total ≤1,5 mg/dl, aspartato transaminasa (AST) y alanina transaminasa (ALT) ≤2,5 veces el límite superior de la normalidad (LSN) [o 5,0 veces LSN en caso de metástasis hepática], y alcalina fosfatasa ≤2,5 veces el LSN (o 5,0 veces el LSN en caso de metástasis hepática).
9. El paciente tiene una función renal adecuada según se define mediante una creatinina sérica ≤ 1,5 veces superior al LSN, aclaramiento de la creatinina (medido o calculado) ≥60 ml/min, o albúmina sérica ≥ al límite inferior de la normalidad del rango normal institucional (LIN).
10. Los efectos secundarios o toxicidades importantes del paciente de un tratamiento anterior (cirugía, radioterapia) deben haberse aliviado hasta un nivel estable o crónico (grado 1).
11. El paciente está de acuerdo en la utilización de un método anticonceptivo adecuado durante el tiempo del estudio y hasta 4 semanas después de la última dosis del tratamiento del estudio. Los pacientes deben avisar al investigador principal si sus parejas o las mismas pacientes se han quedado embarazadas.
12. El paciente ha otorgado un consentimiento informado firmado.

E.4

Principal exclusion criteria

1. El paciente ha recibido quimioterapia sistémica previa para CCR localmente avanzado no extirpable o metastásico. (La quimioterapia adyuvante previa está permitida si se ha confirmado la progresión de la enfermedad (incluyendo los marcadores tumorales séricos) > 6 meses después de finalizar el último ciclo de quimioterapia adyuvante o ≥ 12 meses para pautas de tratamiento que contengan oxaliplatino.)
2. El paciente ha recibido radioterapia previa en > 25% de la médula ósea. (Se permite la radioterapia como parte de una quimiorradioterapia adyuvante estándar para el cáncer de recto > 6 meses antes de la inclusión en el estudio.)
3. El paciente tiene metástasis cerebral confirmada o sintomática.
4. El paciente ha participado en estudios clínicos en las 12 semanas previas a la inclusión en el estudio con fármacos o intervenciones experimentales no aprobados.
5. El paciente ha recibido tratamiento previo con anticuerpos monoclonales.
6. El paciente ha recibido tratamiento previo con algún medicamento agonista del receptor del factor de crecimiento epidérmico.
7. El paciente tiene condiciones médicas concomitantes graves que incluyan infección activa no controlada o cardiopatía, que según la opinión del investigador pudieran comprometer al paciente o al estudio.
8. El paciente tiene tratamiento crónico durante > 6 meses con corticosteroides no tópicos en dosis > 10 mg/día prednisona o equivalente antes de la inclusión en el estudio, que según la opinión del investigador pudiera comprometer al paciente o al estudio.
9. El paciente tiene deficiencia conocida de dihidropirimidina deshidrogenasa (DPD).
10. El paciente tiene alergia conocida a alguno de los componentes del tratamiento.
11. El paciente tiene oclusión intestinal aguda o subaguda.
12. El paciente tiene neuropatía periférica ≥ grado 2 (criterios comunes de terminología para acontecimientos adversos del National Cancer Institute [NCI-CTCAE], versión 3.0).
13. El paciente tiene antecedentes de otras neoplasias malignas, con la excepción de cáncer de piel no melanoma o carcinoma in situ de cuello uterino tratados con intención curativa.
14. El paciente, si es mujer, está embarazada (confirmado mediante prueba de orina o prueba beta-gonadotropina coriónica sérica humana [βHCG]) o es lactante.
15. El paciente ha recibido un autotransplante o alotransplante de tejido u órgano previo.
16. El paciente tiene neumonía intersticial o fibrosis pulmonar intersticial.
17. El paciente tiene derrame pleural o ascitis que provoque disnea ≥ grado 2.
18. El paciente tiene condiciones psicológicas, familiares, sociológicas o geográficas que no permitan un seguimiento del estudio, un cumplimiento con el protocolo o una firma del consentimiento informado adecuados.

E.5 End points

E.5.1

Primary end point(s)

Criterios de evaluación:
Eficacia: Respuesta tumoral (RC + RP) según los criterios RECIST cada 4 ciclos, supervivencia global, supervivencia sin progresión, duración de la respuesta.
Tolerancia: Acontecimientos adversos (CTCAE del NCI versión 3.0), acontecimientos adversos graves, exploraciones físicas, medición de los signos vitales, evaluaciones de laboratorio clínico, e interrupción del tratamiento debido a toxicidad.

Farmacocinética: Los parámetros incluyen pero no están limitados a cmax, ABC, t½, IC, Vss de IMC-11F8 utilizando métodos no compartamentales.
Inmunogenia: Determinación de anticuerpos anti-IMC-11F8.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

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

Yes

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

E.8.1.1

Randomised

E.8.1.2

Open

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.8.3

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

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

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	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
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	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	24
F.4.2	For a multinational trial
F.4.2.1	In the EEA	40
F.4.2.2	In the whole clinical trial	40

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

2007-06-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-05-14

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2010-10-29

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