Clinical Trials Register

Summary
EudraCT Number:	2010-020606-15
Sponsor's Protocol Code Number:	AIO-STO-0309
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:	2013-02-04
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

2010-020606-15

A.3

Full title of the trial

An open-label, randomized phase III trial of cisplatin and 5-fluorouracil with or without panitumumab for patients with nonresectable, advanced or metastatic esophageal squamous cell cancer

Ensayo clínico abierto, aleatorizado, de fase III, de cisplatino y 5-fluorouracilo con o sin panitumumab, en pacientes con carcinoma esofágico de células escamosas (ESCC) avanzado o metastásico, no resecable.

A.3.1

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

An open-label, randomized phase III trial of cisplatin and 5-fluorouracil with or without panitumumab for patients with nonresectable, advanced or metastatic esophageal squamous cell cancer

A.3.2

Name or abbreviated title of the trial where available

POWER

A.4.1

Sponsor's protocol code number

AIO-STO-0309

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	AIO-Studien-gGmbH
B.1.3.4	Country	Germany
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	Amgen GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AIO-Studien-gGmbH
B.5.2	Functional name of contact point	AIO-Studien-gGmbH
B.5.3	Address:
B.5.3.1	Street Address	Kuno-Fischer-Straße 8
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	14057
B.5.3.4	Country	Germany
B.5.4	Telephone number	4930322932941
B.5.5	Fax number	4930322932943
B.5.6	E-mail	gmbh@aio-portal.de

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	Vectibix
D.2.1.1.2	Name of the Marketing Authorisation holder	Amgen Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Panitumumab
D.3.4	Pharmaceutical form	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	Panitumumab
D.3.9.1	CAS number	339177-26-3
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	20
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	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	monoclonal antibody

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

Patients with nonresectable, advanced or metastatic esophageal squamous cell cancer (ESCC)

en pacientes con carcinoma esofágico de células escamosas (ESCC) avanzado o metastásico, no resecable

E.1.1.1

Medical condition in easily understood language

nonresectable, advanced or metastatic esophageal cancer

carcinoma esofágico de células escamosas (ESCC) avanzado o metastásico, no resecable.

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	15.1
E.1.2	Level	LLT
E.1.2	Classification code	10015363
E.1.2	Term	Esophageal cancer NOS
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	15.1
E.1.2	Level	LLT
E.1.2	Classification code	10062478
E.1.2	Term	Esophageal cancer metastatic
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	15.1
E.1.2	Level	PT
E.1.2	Classification code	10055102
E.1.2	Term	Oesophageal cancer metastatic
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	15.1
E.1.2	Level	LLT
E.1.2	Classification code	10030152
E.1.2	Term	Oesophageal cancer NOS
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

To demonstrate superiority of 5-fluorouracil, cisplatin and panitumumab over 5-fluorouracil and cisplatin alone in terms of overall survival in esophageal cancer

Demostrar la superioridad de 5-fluorouracilo, cisplatino y panitumumab sobre 5-fluorouracilo y cisplatino sólos, en términos de supervivencia global en el carcinoma esofágico

E.2.2

Secondary objectives of the trial

To compare treatment arms with respect to:
? Progression-free survival
? 1-year survival
? Response rate
? Safety and tolerability
? Quality of Life

Comparar los brazos de tratamiento con respecto a:
? Supervivencia libre de progresión
? Supervivencia al año
? Tasa de respuesta
? Seguridad y tolerabilidad
? Calidad de vida

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed written informed consent
2. Male or female ?18 years of age
3. Histologically proven squamous cell carcinoma of the esophagus, which is not curatively respectable* and not eligible for definitive radiochemotherapy**. Patients with locally recurrent disease or clearly metastatic disease (Tx, Nx, M1, locally unresectable T4, Nx, M0 or TX, N3, M0) or macroscopically residual (post-resection) disease not eligible for definitive radiochemotherapy may be enrolled.
*resectability has to be defined prior to randomization according to local standards:
The tumor is considered unresectable due to:
T-stage, N-stage, performance status/nutritional status, co-morbidity (pulmonary function, other), tumor location upper third of the esophagus, relation to other organs/structures), patient refusal, other reasons.
**eligibility to definitive radiochemotherapy will be determined according to local standards based on the extent of disease, performance status/nutritional status, co-morbidity (pulmonary function, other), volume of neighboring organs within the radiation field, patient refusal, other reasons.
4. Measurable or non-measurable disease according to RECIST 1.1
5. ECOG 0-1
6. Women of child-bearing potential must have a negative pregnancy test
7. Laboratory requirements
? Hematology:
o Absolute neutrophil count ?1.5x109/L
o Platelet count ?100x109/L
o Leukocyte count > 3.0x109/L
o Hemoglobin ? 9 g/dL or 5.59 mmol/l
? Hepatic Function:
o Total bilirubin ? 1.5 time the upper normal limit (UNL)
o AST ? 2.5xUNL in absence of liver metastases, or ?5xUNL in presence of liver metastases
o ALT ? 2.5xUNL in absence of liver metastases, or ?5xUNL in presence of liver metastases
? Renal Function:
o Creatinine clearance ?50 mL/min according to Cockroft-Gault formula
? Metabolic Function
o Magnesium ? lower limit of normal
o Calcium ? lower limit of normal

1. Consentimiento informado por escrito firmado
2. Hombre o mujer de edad ?18 años
3. Carcinoma esofágico de céulas escamosas demostrado histológicamente, no susceptible de resección curativa* ni elegible para radioquimioterapia definitiva**. Pacientes con enfermedad recurrente local o con enfermedad metastásica clara (Tx, Nx, M1, T4 localmente irresecable, Nx, M0 ó TX, N3, M0) ó enfermedad macroscópica residual (post-resección) no susceptible de radioquimioterapia definitiva.
*La resecabilidad debe ser definida previo a la aleatorización de acuerdo con los estándares locales:
El tumor es considerado irresecable debido a:
Estadío-T, estadío-N, estado nutricional/performance status, co-morbilidad (función pulmonar, otra), localización del tumor en el tercio superior del esófago, relación con otros órganos/estructuras), negativa del paciente, otras razones.
**La elegibilidad para radioquimioterapia definitiva se determinará de acuerdo con los estándares locales basados en la extensión de la enfermedad, estado nutiricional/performance status, co-morbilidad (función pulmonar, otra), volumen de los órganos adyacentes en el campo de la radiación, negativa del paciente, otras razones.
4. Enfermedad medible o no medible de acuerdo con los criterios RECIST 1.1
5. ECOG 0-1
6. Las mujeres en edad fértil deben tener un test de embarazo negativo.
7. Requisitos de laboratorio
? Hematología:
o Recuento total de neutrófilos ?1.5x109/L
o Recuento plaquetario ?100x109/L
o Recuento leucocitario > 3.0x109/L
o Hemoglobina ? 9 g/dL ó 5.59 mmol/l
? Función hepática:
o Bilirrubina total ? 1.5 veces el límite superior de la normalidad
o GOT ? 2.5 veces el límite superior de la normalidad en ausencia de metástasis hepáticas, ó ?5 veces en presencia de metástasis hepáticas
o GPT ? 2.5 veces el límite superior de la normalidad en ausencia de metástasis hepáticas, ó ?5 veces en presencia de metástasis hepáticas
? Función renal:
o Aclaramiento de creatinina ?50 mL/min de acuerdo con la fórmula de Cockroft-Gault
? Función metabólica:
o Magnesio ? límite inferior de la normalidad
o Calcio ? límite inferior de la normalidad

E.4

Principal exclusion criteria

1. Previous chemotherapy of esophageal cancer except for neoadjuvant treatment without recurrence within 6 months after the end of treatment.
2. Concurrent radiotherapy involving target lesions used for this study. Concurrent palliative radiation for non-target lesions is allowed if other lesions are available outside the involved field. Previous pre-operative or post-operative radiotherapy is allowed.
3. Previous exposure to EGFR-targeted therapy
4. Other previous malignancy with exception of a history of a previous curatively treated basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix or other curatively treated malignant disease without recurrence after at least 5 years of follow-up
5. Known brain metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and steroids
6. Serious concomitant disease or medical condition that in the judgment of the investigator renders the subject at high risk of treatment complication or reduces the probability of assessing clinical effect.
7. Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ? 1 year before enrolment
8. Inadequate pulmonary function according to the Investigator?s judgment, history of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan.
9. Hearing loss > NCI-CTC V.4.0.3 Grade 3
10. Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.
11. Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment.
12. Contraindications to receive any platin, 5-FU or panitumumab
13. Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to treatment start
14. Known drug abuse/alcohol abuse
15. peripheral polyneuropathy > NCI-CTC V 4.03 Grade 2
16. chronic inflammatory bowels diseases
17. Social situations limiting the compliance with the study requirements

Pacientes con cualquiera de los siguientes criterios no serán elegibles para participar:
1. Quimioterapia previa de carcinoma esofágico metastásico. La quimioterapia neoadyuvante previa ó la radioquimioterapia definitiva sin recurrencia de la enfermedad dentro de los 6 meses después de la finalización del tratamiento, se permiten.
2. Radioterapia concurrente que afecte a lesiones diana empleadas en este estudio. La radiación paliativa concurrente para lesiones no diana se permite si existen otras lesiones fuera del campo implicado. Se permite la radioterapia pre- o post-quirúrgica previa.
3. Exposición previa a tratamiento dirigido al EGFR.
4. Otro proceso maligno previo, con la excepción de historial de tratamiento curativo de carcinoma cutáneo de células basales o carcinoma pre-invasivo de cérvix, o cualquier otro proceso maligno tratado curativamente sin recurrencia al menos en 5 años de seguimiento.
5. Metástasis cerebrales conocidas, salvo que hayan sido tratadas adecuadamente (cirugía o radioterapia) sin evidencia de progresión, y neurológicamente estables sin tratamiento anticonvulsivante ni esteroides.
6. Enfermedad concomitante grave o condición médica que, a juicio del investigador, implica colocar al/ a la paciente en situación de alto riesgo para sufrir complicaciones al tratamiento, o reduce la probabilidad de valorar su efecto clínico.
7. Enfermedad cardiovascular clínicamente significativa (incluyendo infarto de miocardio, angina inestable, fallo cardíaco congestivo sintomático, arritmia cardíaca incontrolada grave) ? 1 año antes de la inclusión.
8. Función pulmonar inadecuada a juicio del Investigador, historial de enfermedad pulmonar intersticial p.ej. neumonitis o fibrosis pulmonar, o evidencia de enfermedad pulmonar intersticial en la TC de tórax basal.
9. Pérdida de audición > Grado 3 de NCI-CTC V.4.03.
10. Mujer embarazada o lactante, o con intención de quedarse embarazada en los 6 meses siguientes a la finalización del tratamiento.
11. Sujeto (hombre o mujer) que no esté dispuesto a emplear métodos anticonceptivos altamente eficaces (de acuerdo con los estándares institucionales) durante el tratamiento y en los 6 meses (hombre o mujer) siguientes a la finalización del tratamiento.
12. Contraindicación a recibir cualquier platino, 5-fluorouracilo o panitumumab.
13. Tratamiento simultáneo con otros fármacos en investigación o participación en cualquier otro ensayo clínico con un fármaco en investigación en los 30 días previos al inicio del tratamiento.
14. Abuso conocido de alcohol/drogas.
15. Polineuropatía periférica > Grado 2 de NCI-CTC V 4.03.
16. Enfermedad inflamatoria intestinal crónica.
17. Situaciones sociales que puedan limitar el cumplimiento de los requisitos del estudio.

E.5 End points

E.5.1

Primary end point(s)

Overall survival

Supervivencia global

E.5.1.1

Timepoint(s) of evaluation of this end point

Date of death

Fecha de exitus

E.5.2

Secondary end point(s)

1 Progression-free survival
2 1-year survival
3 Response rate
4 Safety and tolerability
5 Quality of Life

1 Supervivencia libre de progresión
2 Supervivencia al año
3 Tasa de respuesta
4 Seguridad y tolerabilidad
5 Calidad de vida

E.5.2.1

Timepoint(s) of evaluation of this end point

1 between randomisation and determination of progressive disease
2 One year after randomisation
3 between randomisation and end of treatment visit
4 between randomisation and end of treatment visit
5 randomisation, followed by every cycle until end of treatment visit

1 entre la randomisación y la confirmación de la progresión de la enfermedad
2 un año despues la randomisación
3 entre la randomisación y la visita de fin de tratamiento
4 entre la randomisación y la visita de fin de tratamiento
5 randomisación, seguida de cada siglo hasta la visita de fin de tratamiento

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

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)

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Standard Chemotherapy

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

12 months after last patient randomised

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:

150

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

150

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

300

F.4.2.2

In the whole clinical trial

300

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)

no difference from the expected normal treatment of that condition

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

2013-04-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-02-08

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

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IMP with orphan designation in the indication
Orphan Designation Number:
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