Clinical Trials Register

Summary
EudraCT Number:	2015-003312-21
Sponsor's Protocol Code Number:	GECP15/02
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:	2015-12-10
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2015-003312-21

A.3

Full title of the trial

Phase II clinical trial with tri-weekly metronomic oral vinorelbine and cisplatin as induction treatment for and subsequent concomitant with radiotherapy (RT) in patients with non small cell lung cancer (NSCLC) locally advanced unresectable.

Ensayo clínico fase II con vinorelbina oral metronómica y cisplatino trisemanal como tratamiento de inducción y posterior concomitancia con radioterapia (RT) en pacientes con cáncer de pulmón no microcítico (CPNM) localmente avanzado irresecable.

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

NORA

A.4.1

Sponsor's protocol code number

GECP15/02

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	Grupo Español de Cáncer de Pulmón
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	Grupo Español de Cáncer de Pulmón
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	Grupo Español de Cáncer de Pulmón
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	C/ Villarroel, 251
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08036
B.5.3.4	Country	Spain
B.5.4	Telephone number	34934302006
B.5.5	Fax number	3493419 1768
B.5.6	E-mail	epereira@gecp.org

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	Navelbine
D.2.1.1.2	Name of the Marketing Authorisation holder	Pierre Fabre Ibérica, 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.3.4	Pharmaceutical form	Capsule, soft
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	VINORELBINE
D.3.9.1	CAS number	71486-22-1
D.3.9.2	Current sponsor code	NAVELBINE ORAL
D.3.9.3	Other descriptive name	VINORELBINE
D.3.9.4	EV Substance Code	SUB00069MIG
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)	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	CISPLATINO Accord
D.2.1.1.2	Name of the Marketing Authorisation holder	Accord Healthcare S.L.U.
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	CISPLATINO
D.3.2	Product code	CISPLATINO
D.3.4	Pharmaceutical form	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	CISPLATIN
D.3.9.1	CAS number	15663-27-1
D.3.9.2	Current sponsor code	CISPLATIN
D.3.9.3	Other descriptive name	CISPLATIN
D.3.9.4	EV Substance Code	SUB07483MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	80
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

Unresectable locally advanced non-small cell lung cancer.

Cancer de Pulmón no microcítico localmente avanzado irresecable

E.1.1.1

Medical condition in easily understood language

Non-operable and advanced lung cancer

Cancer de Pulmón avanzado y no operable

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	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10025053
E.1.2	Term	Lung cancer non-small cell stage IIIA
E.1.2	System Organ Class	100000004864

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 evaluate the efficacy in terms of progression-free survival (PFS) of oral metronomic vinorelbine and cisplatin as an induction treatment and posteriorly with concomitant radiotherapy. The PFS is defined as the time since the randomization until the progression documentation or exitus for any reason ( any death with or without evidence of progression, will be considered events on the exitus date and these that will not progress in the moment of the analysis will be censored with the date of the last control).

? Evaluar la eficacia en términos de supervivencia libre de progresión (SLP) de vinorelbina oral metronómica y cisplatino como tratamiento de inducción y después con radioterapia concomitante. Se define la SLP como el tiempo desde el momento de la aleatorización hasta la documentación de la progresión o éxitus por cualquier causa (es decir, los pacientes que fallezcan sin evidencia de progresión, serán considerados eventos en la fecha de éxitus y aquellos que tampoco hayan progresado en el momento del análisis, serán censurados con fecha de último control

E.2.2

Secondary objectives of the trial

?To describe the objective response rate of the treatment, by the target lesion assessment according with the RECIST criteria (version 1.1).
?To describe the treatment overall survival (OS). Calculated from the randomization until the death of the patient. In case that the follow-up of the patient will be lost, it will be considered the last date that it was known that the patient was alive for last time as a date for determine the survival.
?To describe the response duration time, determined since the date that it is objectified the tumor response until the progression is documented.
?To describe the safety of the treatment.

?Describir la tasa de respuestas objetivas del tratamiento.
?Describir la tasa de control de la enfermedad.
?Describir el tiempo de duración de la respuesta.
?Describir el tiempo de duración del control de la enfermedad.
?Describir la supervivencia global (SG) del tratamiento.
?Describir la seguridad del tratamiento.
?Describir la tasa de adherencia al tratamiento oral.
?Análisis de biomarcadores

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Patients with confirmed histologic diagnosis of NSCLC?s in stage IIIA and IIIB unresectables.
-Realization of a basal PET-CT that dismisses the presence of distant disease and confirm that it is a NSCLC not candidate to radical surgery treatment. The positive mediastinal lymph nodes for PET-CT have to be confirmed histologically. It could be considered affected mediastinic lymph nodes without necessity of verify histologically, when there is a mass at the lymph nodes area without distinguished edges.
-Disease measurable by CT, as minimum one lesion.
-Performance status ECOG 0-1.
-Life expectation > 12 weeks.
-Age ?18 years and ? 75 years.
-Satisfactory renal function: creatinine ? 1.5 mg/dl or creatinine clearance > 60 ml/min.
-Correct hematological function: Hemoglobin > 10 g/dl, neutrophils ? 1500, platelets ? 100000.
-Correct liver function: bilirubin ? 1.5 times the maximum limit of the normality, transaminases ? 2.5 over the upper limit of the normality.
-Correct lung function: defined by forced expired volume in 1 second (FEV1) >50% of normal volume, and lung diffusing capacity for carbon monoxide (DLCO) > 40% of normal value.
-Lung normal proportion exposed to >20 Gy of RT (V20) have to be ? 35%.
-Informed consent signature

-Pacientes con reciente diagnóstico histológico de CPNM en estadio IIIA y IIIB irresecable.
-Realización de una PET-TC basal que descarte la presencia de enfermedad a distancia y confirme que se trata de un CPNM no tributario de tratamiento quirúrgico radical.
-Las adenopatías mediastínicas positivas por PET-TC deberán ser confirmadas histológicamente. Se podrá considerar afectación mediastínica sin necesidad de constatar histológicamente cuando exista una masa de ganglios linfáticos en los que no se distinguen los márgenes.
-Al menos una lesión medible por TC.
-Performance status ECOG 0-1.
-Esperanza de vida > 12 semanas.
-Edad ?18 años y ? 75 años.
-Correcta función renal: creatinina ? 1.5 mg/dl o aclaramiento de creatinina > 60 ml/min.
-Correcta función hematológica: Hemoglobina >10 g/dl, neutrófilos ? 1500 /mm3 y plaquetas ? 100000 /mm3.
-Correcta función hepática: Bilirrubina ? 1.5 veces el límite máximo de cada centro, transaminasas ? 2.5 por encima del límite de la normalidad.
-Correcta función pulmonar sin broncodilatadores: definida por un volumen espirado forzado en 1 segundo (FEV1) >50% del volumen normal previsto, y una capacidad de difusión pulmonar para monóxido de carbono (DLCO) > 40% del valor normal previsto.
-La proporción de pulmón normal expuesto a >20 Gy de RT (V20) deberá ser ? 35%.
-Firma del consentimiento informado.

E.4

Principal exclusion criteria

-Decrease in weight > 5% in the last 3 months previous to the study entry.
-Intestinal problems that do not ensure a correct absorption of oral vinorelbine.
-Pregnant and lactating women. Women in childbearing age should have a negative pregnancy test, men and women under this condition should use contraceptive measures during all the clinical trial.
-Symptomatic sensory neuropathy > grade 1 according with the toxicity criteria of CTCAE v4.
-Non-controlled comorbidities.
-Superior vena cava syndrome.
-Pleural or pericardial effusion: both will be considered as metastatic disease indicators unless will be demonstrated the opposite. These that have a negative cytological for malignancy, being exudate, will be excluded too. These patients with non-visible pleural effusion in thoracic radiology or so small for realize a safe diagnostic puncture can be included.
-Known hypersensitivity to drugs with similar structure of the study drugs.
-Previous treatment with antineoplastic drugs or previous thoracic radiotherapy for the lung cancer or for other reason. Previous surgery for the lung cancer.
-Personal background of other neoplasia, except cervical or breast carcinoma in situ and the skin basal cell carcinoma, treated in the correct way in a period of less than 5 years.
-Concomitant treatment with any other antineoplastic medicine or in investigation study.
- Patients in any psychological situation, familiar, sociological or geographical that can complicate the correct accomplishment of the study protocol and the following-up program

-Pérdida de peso > 10% en los 3 meses previos a la entrada en el estudio.
-Problemas intestinales que no aseguren una correcta absorción de vinorelbina oral.
-Mujeres embarazadas o lactantes. Las mujeres en edad fértil deberán tener una prueba de embarazo negativa, y tanto hombres como mujeres bajo esta condición deberán tomar medidas anticonceptivas a lo largo del estudio.
-Neuropatía sensorial sintomática > grado 1 según los criterios de toxicidad de la CTCAE v4.
-Comorbilidades no controladas.
-Síndrome de la vena cava superior.
-Derrame pleural o pericárdico: se considerarán ambos como indicativos de enfermedad metastásica a menos que se demuestre lo contrario. Aquellos que aun siendo negativos citológicamente para malignidad, sean exudados, también se excluirán. Se podrá incluir aquellos pacientes con derrame pleural no visible en radiografía de tórax o demasiado pequeños para realizar punción diagnóstica de forma segura.
-Hipersensibilidad conocida a fármacos con estructura similar a la de los fármacos de estudio.
-Tratamiento previo con fármacos antineoplásicos, radioterapia torácica o cirugía previa para el cáncer de pulmón o por otra causa.
-Antecedente de otra neoplasia adecuadamente tratada hace menos de 5 años, exceptuando el carcinoma in situ de cérvix o mama y el carcinoma basocelular cutáneo.
-Tratamiento concomitante con cualquier otro fármaco antineoplásico o en fase de investigación.
-Pacientes en cualquier situación psicológica, familiar, sociológica o geográfica que pueda dificultar el cumplimiento del protocolo del estudio y el programa de seguimiento.
-Historia de alteraciones neurológicas o psiquiátricas que deterioren el conocimiento o impidan otorgar adecuadamente el consentimiento informado

E.5 End points

E.5.1

Primary end point(s)

Progression free survival (PFS)

Supervivencia libre de progresión (SLP)

E.5.1.1

Timepoint(s) of evaluation of this end point

Tiempo desde el momento de la aleatorización hasta el momento de la progresión o éxitus por cualquier causa sin haberse producido la progresión de la enfermedad estudiada. Es decir, los pacientes que fallezcan sin evidencia de progresión, serán considerados eventos en la fecha de éxitus y aquellos que tampoco hayan progresado en el momento del análisis, serán censurados con fecha de último control.

E.5.2

Secondary end point(s)

Describir la tasa de respuesta objetiva mediante la valoración de las lesiones diana según los criterios RECIST (versión 1.1). Describir la SLP en los pacientes incluidos. Describir la supervivencia global en los pacientes incluidos calculada desde la aleatorización y hasta la muerte del paciente. En caso que el seguimiento del paciente se haya perdido se considerará la última fecha en la que se conoce que el paciente sigue vivo por última vez como fecha para la determinación de supervivencia.

E.5.2.1

Timepoint(s) of evaluation of this end point

La evaluación del tumor se realizará según las pautas RECIST (versión 1.1). La evaluación de una lesión medible se realizará en el momento basal y a las 4 semanas de la finalización del tratamiento. Los pacientes que suspendan el tratamiento del protocolo por otro motivo distinto de progresión de la enfermedad se someterán a valoraciones tumorales cada 6 semanas a partir del momento de la aleatorización hasta que se cumplan los criterios RECIST revisados (versión 1.1) sobre progresión de la enfermedad.

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)

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

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)

Yes

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

It is defined as the end of the study the progression documentation of the last patient. For the analysis of the secondary objective of OS, it will be necessary the quarterly follow-up of the patients during minimum of 24 months more from the last documented progression.

Se define como finalización del estudio la documentación de éxitus del último paciente o el fin del periodo de seguimiento. Para el análisis del objetivo secundario de SG, será necesario el seguimiento trimestral de los pacientes durante al menos 24 meses más a partir de la última inclusión.

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

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)

Yes

F.1.3.1

Number of subjects for this age range:

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

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)

Please see on the protocol study

Por favor ver en el protocolo del estudio

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

2015-12-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-11-23

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-12-16

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