Clinical Trials Register

Summary
EudraCT Number:	2015-001407-31
Sponsor's Protocol Code Number:	D5160C00022
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:	2015-07-10
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

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2015-001407-31

A.3

Full title of the trial

Open Label, Multinational, Multicenter, Real World Treatment Study of Single Agent AZD9291 for Patients with Advanced/Metastatic Epidermal Growth Factor Receptor (EGFR) T790M Mutation-Positive Non-Small Cell Lung Cancer (NSCLC) Who Have Received Prior Therapy with an EGFR Tyrosine Kinase Inhibitor (EGFR-TKI)

Estudio abierto, multinacional y multicéntrico, acerca del tratamiento en la
práctica real con AZD9291 en monoterapia en pacientes con Cáncer de pulmón
no microcítico (CPNM) con la mutación T790M del receptor del factor de crecimiento epidérmico (EGFR), avanzado/metastásico, que han recibido
previamente tratamiento con un inhibidor de la tirosina cinasa del EGFR
(EGFR-TKI)

A.3.1

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

Real World Treatment Study of AZD9291 for Advanced/Metastatic EGFR T790M Mutation (NSCLC)

Estudio acerca del tratamiento en la práctica real con AZD9291 para la mutación T790M Avanzada/Metastática EGFR T790M , en cáncer de pulmón no microlítico (CPNM)

A.3.2

Name or abbreviated title of the trial where available

ASTRIS

A.4.1

Sponsor's protocol code number

D5160C00022

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	AstraZeneca AB
B.1.3.4	Country	Sweden
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	AstraZeneca AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AstraZeneca
B.5.2	Functional name of contact point	Information Center
B.5.3	Address:
B.5.3.1	Street Address	USA
B.5.3.2	Town/ city	USA
B.5.3.3	Post code	USA
B.5.3.4	Country	United States
B.5.4	Telephone number	+34 91 391 34 43
B.5.6	E-mail	information.centre@astrazeneca.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.3.1	Product name	AZD9291 40 mg film-coated tablet
D.3.2	Product code	AZD9291
D.3.4	Pharmaceutical form	Film-coated tablet
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	Not yet assigned
D.3.9.1	CAS number	1421373-66-1
D.3.9.2	Current sponsor code	AZD9291 mesylate
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	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.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	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.3.1	Product name	AZD9291 80 mg film-coated tablet
D.3.2	Product code	AZD9291
D.3.4	Pharmaceutical form	Film-coated tablet
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	Not yet assigned
D.3.9.1	CAS number	1421373-66-1
D.3.9.2	Current sponsor code	AZD9291 mesylate
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	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

Stage IIIB or IV EGFRm NSCLC with T790M positive mutation

Estadio IIIB o metastásico (estadio IV) CPNM, con mutación positiva T790M del EGFRm

E.1.1.1

Medical condition in easily understood language

Specific type of lung cancer called "non-small cell lung cancer" NSCLC

Tipo específico de cáncer de pulmón llamado "cáncer de pulmón
no microcítico" (CPNM)

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	18.0
E.1.2	Level	PT
E.1.2	Classification code	10029521
E.1.2	Term	Non-small cell lung cancer stage IIIB
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	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10025055
E.1.2	Term	Lung cancer non-small cell stage IV
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

The primary objective of this study is to assess the efficacy and safety of single agent AZD9291 in a real world setting in adult patients with advanced or metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive Non-Small Cell Lung Cancer (NSCLC), who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy.

El objetivo principal de este estudio es evaluar la eficacia y la seguridad de la monoterapia con AZD9291 en la práctica real en pacientes adultos con cáncer de pulmón no microcítico (CPNM) con la mutación T790M del receptor del factor de crecimiento epidérmico (EGFR), avanzado/metastásico, que han recibido previamente tratamiento con un inhibidor de la tirosina cinasa del EGFR (EGFR-TKI).

E.2.2

Secondary objectives of the trial

Not applicable

No aplicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Provision of signed and dated written informed consent by the patient or legally acceptable representative prior to any study-specific procedures.
2. Adults (according to each country regulations for age of majority).
3. Locally advanced (stage IIIB) or metastatic (stage IV) EGFRm NSCLC, not amenable to curative surgery or radiotherapy, with confirmation of the presence of the T790M mutation.
4. Prior therapy with an EGFR-TKI. Patients may have also received additional lines of treatment.
5. World Health Organization (WHO) performance status 0-2
6. Adequate bone marrow reserve and organ function as demonstrated by complete blood count, biochemistry in blood and urine at baseline.
7. ECG recording at baseline showing absence of any cardiac abnormality as per exclusion criterion 6.
8. Female patients of childbearing potential must be using adequate contraceptive measures, must not be breast feeding, and must have a negative pregnancy test prior to start of dosing. Otherwise, they must have evidence of nonchildbearing potential as defined below:
a. Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments.
b. Women under 50 years would be consider post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution.
c. Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
9. Male patients must be willing to use barrier contraception, i.e., condoms.

1. Otorgamiento del consentimiento informado por escrito, firmado y fechado, por el paciente o su representante legal, antes de cualquier procedimiento del estudio.
2. Adultos (de acuerdo a la legislación de cada país acerca de la mayoría de edad).
3. CPNM localmente avanzado (estadio IIIB) o metastásico (estadio IV) EGFRm, no susceptible de cirugía o radioterapia curativa, con confirmación de la presencia de la mutación T790M.
4. Tratamiento previo con un inhibidor de la tirosina cinasa del EGFR. También podrán haber recibido otras líneas de tratamiento.
5. Estado funcional de la Organización Mundial de la Salud (OMS) 0-2.
6. Reserva adecuada de médula ósea y función orgánica adecuada, tal como se desprende del hemograma completo y de la bioquímica en sangre y orina en el basal.
7. ECG en el basal sin las anomalías cardíacas recogidas en el criterio de exclusión nº 6.
8. Las mujeres potencialmente fértiles deben estar utilizando métodos anticonceptivos adecuados, no podrán estar amamantando y deberán presentar un resultado negativo de una prueba de embarazo antes del comienzo del tratamiento. En caso contrario, deberán mostrar evidencia de que no pueden concebir, tal como se define a continuación:
a. Posmenopausia, definida como mujer de más de 50 años y amenorreica desde hace como mínimo 12 meses tras la suspensión de todo tratamiento hormonal exógeno.
b. Las mujeres menores de 50 años podrían considerarse posmenopáusicas si han mostrado amenorrea durante 12 meses o más tras la suspensión de todo tratamiento hormonal exógeno y unos niveles de hormona luteinizante y de hormona foliculoestimulante en el rango posmenopáusico de la institución.
c. Documentación de esterilización quirúrgica irreversible por histerectomía, ovariectomía bilateral o salpingectomía bilateral, pero no por ligadura tubárica.
9. Los pacientes varones deberán estar conformes en utilizar un método anticonceptivo de barrera, esto es, preservativo.

E.4

Principal exclusion criteria

1. Previous (within 6 months) or current treatment with AZD9291.
2. Patients currently receiving (or unable to stop use at least 1 week prior to receiving the first dose of AZD9291) any treatment known to be potent inhibitors or inducers of cytochrome P450 (CYP) 3A4.
3. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, active infection including hepatitis B, hepatitis C and human immunodeficiency virus, or significantly impaired bone marrow reserve or organ function, including hepatic and renal impairment, which in the investigator?s opinion
would significantly alter the risk/benefit balance.
4. Patient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids to manage CNS symptoms within the 2 weeks prior to start AZD9291 administration.
5. Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD.
6. Any of the following cardiac criteria:
a. Mean resting corrected QT interval (QTcF) > 470 ms using Fredericia?s formula.
b. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block).
c. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events.
7. Any unresolved toxicity from prior therapy CTCAE > grade 3 at the time of starting treatment.
8. History of hypersensitivity to excipients of AZD9291 or to drugs with a similar chemical structure or class to AZD9291.

1. Tratamiento previo (en los 6 meses anteriores) o actual con AZD9291.
2. Tratamiento actual (o imposibilidad de su suspensión como mínimo una semana antes de la recepción de la primera dosis de AZD9291) con productos que se sabe que son potentes inhibidores o inductores del citocromo P450 (CYP) 3A4 (Apéndice C).
3. Cualquier signo de enfermedad sistémica severa o no controlada, tal como hipertensión no controlada, diátesis hemorrágica activa, infección activa (como hepatitis B y C y virus de la inmunodeficiencia humana), o afectación importante de la reserva de médula ósea o de función orgánica (como insuficiencia hepática o renal) que, en opinión del investigador,
pudiera influir de manera significativa sobre el balance riesgo/beneficio.
4. Metástasis sintomáticas en sistema nervioso central (SNC) en un paciente
neurológicamente inestable o que ha precisado dosis crecientes de corticosteroides para el control de los síntomas en SNC en el plazo de las 2 semanas previas al comienzo de la administración de AZD9291.
5. Antecedentes de neumopatía intersticial (NPI), NPI de origen farmacológico, neumonitis por radiación que precisó tratamiento con corticoides, o cualquier signo de NPI clínicamente activa.
6. Cualquiera de los siguientes criterios cardíacos:
a. Valor medio del intervalo QT corregido (QTcF) > 470 ms utilizando la fórmula de Fridericia.
b. Cualquier anomalía clínicamente importante del ritmo, la conducción o la
morfología del ECG en reposo (por ejemplo, bloqueo completo de rama izquierda, bloqueo auriculoventricular de tercer grado, bloqueo auriculoventricular de segundo grado).
c. Cualquier factor que pueda aumentar el riesgo de prolongación del QTc o el riesgo de arritmia.
7. Toda toxicidad no resuelta de un tratamiento previo que sea de Grado ?3 de los CTCAE en el momento de ir a comenzar el tratamiento.
8. Antecedentes de hipersensibilidad a los excipientes de AZD9291, o a fármacos de estructura química o familia similar a la de AZD9291.

E.5 End points

E.5.1

Primary end point(s)

Investigator-reported efficacy (including tumor response and disease progression), overall survival (OS), patient-reported lung cancer symptoms.

Eficacia reportada por el Investigador (incluyendo la respuesta tumoral y la progresión de la enfermedad), la supervivencia global (SG), los síntomas del cáncer de pulmón reportados por los pacientes.

E.5.1.1

Timepoint(s) of evaluation of this end point

At baseline and every 6 weeks from randomization until progression and 30 days post last dose.

Al inicio del estudio y cada 6 semanas desde la aleatorización hasta la progresión y 30 días después de la última dosis.

E.5.2

Secondary end point(s)

Not applicable.

No aplicable

E.5.2.1

Timepoint(s) of evaluation of this end point

Not applicable.

No aplicable

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

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

110

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

LVLS

Última visita del último paciente

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:

1390

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

1160

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

161

F.4.2

For a multinational trial

F.4.2.1

In the EEA

1500

F.4.2.2

In the whole clinical trial

2550

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)

The study will be closed in each participating country as soon as possible following national reimbursement of AZD9291 in that country. Patients withdrawing from the treatment prior to national reimbursement will be followed up as part of this study. At national reimbursement, patients in the study will be offered to consent for enrolment in an extension observational study. Patients on treatment will receive commercial supply until documented disease progression as per investigator assessment.

El estudio se cerrará en cada país, tras el reembolso nacional de AZD9291 en ese país. Los pacientes retirados del tratamiento antes del reembolso nacional, serán objeto de seguimiento como parte del estudio. En el reembolso nacional, se ofrecerá a los pacientes dar consentimiento para la inclusión en un estudio observacional de extensión. Se suminstrará a los pacientes el tratamiento comercial hasta la progresión de la enfermedad documentada según la evaluación del investigador.

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

2015-08-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-08-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-04-18

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