Clinical Trials Register

Summary
EudraCT Number:	2012-001050-25
Sponsor's Protocol Code Number:	CAUY922A2207
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:	2012-07-26
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

2012-001050-25

A.3

Full title of the trial

A multicenter, open-label, randomized phase II study to evaluate the efficacy of AUY922 vs pemetrexed or docetaxel in NSCLC patients with EGFR mutations who have progressed on prior EGFR TKI treatment

Estudio de fase II, aleatorizado, multicéntrico y abierto, para evaluar la eficacia de AUY922 frente a pemetrexed o docetaxel en pacientes con NSCLC con mutaciones del EGFR que han progresado a tratamiento previo con TKIs del EGFR

A.3.1

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

An open-label, randomized phase II study to evaluate the efficacy of AUY922 vs pemetrexed or docetaxel in NSCLC patients with EGFR mutations

Ensayo abierto, aleatorizado, fase II para evaluar la eficacia de AUY922 frente a pemetrexed o docetaxel en pacientes con NSCLC con mutaciones en el EGFR

A.4.1

Sponsor's protocol code number

CAUY922A2207

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	Novartis Farmaceutica 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	Novartis Pharma Services AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Farmaceutica S.A
B.5.2	Functional name of contact point	Javier Malpesa
B.5.3	Address:
B.5.3.1	Street Address	Gran Via de les Corts Catalanes, 764
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08080
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34933044464
B.5.5	Fax number	+34933064290
B.5.6	E-mail	eecc.novartis@novartis.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	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	AUY922
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	AUY922
D.3.9.2	Current sponsor code	AUY922
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)	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	Comparator
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.2.5	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	pemetrexed
D.3.4	Pharmaceutical form	Powder for 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	PEMETREXED
D.3.9.1	CAS number	137281-23-3
D.3.9.4	EV Substance Code	SUB09655MIG
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	25
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: 3
D.1.2 and D.1.3	IMP Role	Comparator
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.2.5	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	docetaxel
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	DOCETAXEL
D.3.9.1	CAS number	114977-28-5
D.3.9.4	EV Substance Code	SUB12492MIG
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	40
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

NSCLC

Cancer de pulmón de células no pequeñas

E.1.1.1

Medical condition in easily understood language

lung cancer

Cancer de pulmón

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

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

To compare PFS in patients with advanced NSCLC whose tumors harbor EGFR activating mutations and have progressed on EGFR TKI treatment treated with AUY922 versus pemetrexed or docetaxel.

Comparar la Supervivencia Sin Progresión (PFS) en pacientes tratados con AUY922 frente a pemetrexed o docetaxel en base a la evaluación del investigador local por RECIST 1.1. Este estudio también evaluará la Supervivencia Global (SG) entre los grupos de tratamiento realizando el seguimiento de la supervivencia de los pacientes en intervalos de 3 meses

E.2.2

Secondary objectives of the trial

- To compare OS between the treatment arms
- To compare the Overall Response Rate (ORR) between the treatment arms
- To compare the Disease Control Rate (DCR) duration between the treatment arms
- To compare Time to Progression (TTP) between the treatment arms
- To compare Duration of Response (DOR) between the treatment arms
- To evaluate safety and tolerability of administering AUY922 in the treatment of NSCLC compared to pemetrexed or docetaxel
- To perform exploratory evaluations on available tumor-tissue for biological or genomic determinants of outcome, included but not limited to acquired resistance mechanism to EGFR TKI such as T790M mutation or cMet amplification

Otros objetivos secundarios del estudio compararán la Tasa de Respuesta Global (ORR), la tasa de control de la enfermedad (DCR), el tiempo hasta la progresión (TTP) y la duración de la respuesta (DOR) en base a la evaluación por el investigador local por RECIST 1.1. El estudio también evaluará la toxicidad y la tolerabilidad de la administración de AUY922 en el tratamiento de NSCLC en comparación con pemetrexed o docetaxel evaluando la tasa de acontecimientos adversos (AAs), AAs graves (AAGs), cambios en los valores de hematología y bioquímica, constantes vitales, electrocardiogramas (ECGs), interrupciones de dosis, reducciones e intensidad de la dosis entre grupos de tratamiento

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. patients with histologically or cytologically documented, locally advanced (stage IIIB who are amenable to combined modality treatment) or recurrent or metastatic (Stage IV) non-small cell lung cancer.
2. Patients that have EGFR gene mutation in their tumors
3. Patients must have documented clinical benefit (CR, PR, or patients with SD for 6 months or greater) on prior EGFR TKI (e.g. erlotinib or gefitinib) followed by documented progression according to RECIST.
4. Patients must be suitable and willing to undergo mandatory baseline biopsy according to treating institution's own guidelines and requirements for such procedure.

?Pacientes con cáncer de pulmón de células no pequeñas histológicamente o citológicamente documentado, localmente avanzado (estadio IIIB que no son aptos para la modalidad combinada de tratamiento) o recurrente o metastásica (Estadio IV).
?Los pacientes deben tener mutación del gen EGFR en sus tumores.
?Los pacientes deben tener beneficio clínico documentado (RC, RP, o EE durante 6 meses o más) en TKI del EGFR previo (p.e. erlotinib o gefitinib) seguido por progresión documentada por RECIST.
?Los pacientes deben tener 18 años o más y ser capaces de firmar el Consentimiento Informado.
?Los pacientes deben ser adecuados y aceptar seguir una biopsia basal obligatoria según las guías y requisitos propios del centro que realiza el tratamiento para dicho procedimiento. No son obligatorias las biopsias basales para pacientes con mecanismos de resistencia conocida a TKI del EGFR y material tumoral disponible.
?Estado de actividad de la OMS de 0-1.
?Enfermedad medible según los criterios RECIST v.1.1 (las lesiones irradiadas no se pueden considerar medibles a menos que hayan progresado claramente desde la radioterapia).

E.4

Principal exclusion criteria

1. Patients who have received more than two prior lines of antineoplastic therapy for advanced disease.
2. Evidence of spinal cord compression or current evidence of CNS metastases. Screening CT/MRI of the brain is mandatory.
3. Prior treatment with an HSP90 inhibitor.

?Los pacientes que han recibido más de dos líneas de terapia previa por enfermedad avanzada. La quimioterapia administrada como tratamiento adyuvante más de 6 meses antes de la inclusión en el estudio no se considera una línea de terapia previa para los objetivos de este estudio.
?Los pacientes no deben haber recibido tratamiento antineoplásico entre la retirada del TKI del EGFR y el inicio del estudio.
?Evidencia de compresión de médula espinar o evidencia actual de metástasis de SNC. Es obligatorio el TC/IRM del cerebro de selección.
?Los pacientes no deben haber recibido el agente o metabolitos activos para TKI del EGFR (p.e. erlotinib, gefirinib) durante ? 5 vidas medias del inicio del estudio. Todas las toxicidades asociadas (a excepción de la alopecia) deben ser resueltas al nivel basal o menos antes del inicio del estudio.
?Los pacientes no deben haber recibido radioterapia para el control de la enfermedad local durante cuatro semanas. Todas las toxicidades asociadas (a excepción de la alopecia) deben ser resueltas a grado 1 o menos ants del inicio del estudio.
?Tratamiento previo con un inhibidor de HSP90.

E.5 End points

E.5.1

Primary end point(s)

Progression free survival (PFS) based on local investigator assessment per RECIST 1.1

Supervivencia libre de progresión (SLP) basada en la evaluación local del tumor según criterios RECIST 1.1

E.5.1.1

Timepoint(s) of evaluation of this end point

durarion of the treatment

duración del tratamiento

E.5.2

Secondary end point(s)

1. overall survival (OS)
2. overall response rate (ORR)
3. disease control rate (DCR)
4. time to progression (TTP)
5. duration of response (DOR)
6. rate of adverse events (AEs)
7. rate of serious adverse events (SAEs)

1. supervivencia globla (SG)
2. tasa de respuesta global (ORR)
3. tasa de control de la enfermedad (DCR)
4. tiempo hasta progresión (TTP)
5. duración de la respuesta (DOR)
6. tasa de acontecimientos adversos (AEs)
7. tasa de acontecimientos adversos graves (SAEs)

E.5.2.1

Timepoint(s) of evaluation of this end point

1. from randomization to death
2-7. treatment duration

1. Desde la randomización hasta la muerte
2-7. Duración del 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

Yes

E.6.13.1

Other scope of the trial description

compare efficacy of AUY922 versus pemetrexed or docetaxel

Compara la eficacia de AUY922 frente a pemetrexed o docetaxel

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

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

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

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

France

Hong Kong

Israel

Italy

Korea, Republic of

Netherlands

Norway

Poland

Singapore

Spain

Taiwan

United Kingdom

United States

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 continue until one year past last patient treatment unless survival follow up period has already been completed.

El estudio continuará hasta un año después que el último paciente bajo seguimiento de supervivencia haya finalizado.

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)

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

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

F.4.2.2

In the whole clinical trial

120

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)

None

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

2012-10-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-10-05

P. End of Trial
P.	End of Trial Status	Completed

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IMP with orphan designation in the indication
Orphan Designation Number:
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