Clinical Trials Register

Summary
EudraCT Number:	2015-000617-43
Sponsor's Protocol Code Number:	CLEE011F2301
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:	2015-05-08
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

2015-000617-43

A.3

Full title of the trial

MONALEESA-3: A randomized double-blind, placebocontrolled study of ribociclib in combination with fulvestrant for the treatment of postmenopausal women with hormone receptor positive, HER2-negative, advanced breast cancer who have received no or only one line of prior endocrine treatment

Estudio aleatorizado, doble ciego, controlado con placebo de ribociclib en combinación con fulvestrant para el tratamiento de mujeres postmenopáusicas con cáncer de mama avanzado con receptor hormonal positivo, HER2-negativo que no han recibido o que sólo han recibido una línea de tratamiento endocrino previa

A.3.1

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

Study of Efficacy and Safety of LEE011 with endocrine treatment in Postmenopausal Women with Advanced Breast Cancer

Estudio que evalúa la eficacia y la seguridad de LEe011 con el tratamiento endocrino en mujeres posmenopáusicas con cáncer de mama avanzado

A.3.2

Name or abbreviated title of the trial where available

Monaleesa-3

A.4.1

Sponsor's protocol code number

CLEE011F2301

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 Farmacéutica, 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 Farmacéutica, S.A.
B.5.2	Functional name of contact point	Departamento Médico Oncología (GMO)
B.5.3	Address:
B.5.3.1	Street Address	Gran Vía de les Corts Catalanes, 764
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08013
B.5.3.4	Country	Spain
B.5.4	Telephone number	34900353036
B.5.5	Fax number	34932479903
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	LEE011
D.3.4	Pharmaceutical form	Capsule, hard
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	ribociclib
D.3.9.1	CAS number	1374639-75-4
D.3.9.2	Current sponsor code	LEE011
D.3.9.3	Other descriptive name	LEE011
D.3.9.4	EV Substance Code	SUB31644
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	200
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	Faslodex
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca UK Limited
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	fulvestrant
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	fulvestrant
D.3.9.1	CAS number	129453-61-8
D.3.9.2	Current sponsor code	FULVESTRANT
D.3.9.3	Other descriptive name	FULVESTRANT
D.3.9.4	EV Substance Code	SUB13933MIG
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	250
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

postmenopausal women with HR+, HER2-negative advanced (loco regionally recurrent not amenable to curative therapy or metastatic) breast cancer

mujeres postmenopáusicas con cáncer de mama avanzado HR+, HER2-negativo que no han recibido o que sólo han recibido un tratamiento endocrino previo para la enfermedad avanzada.

E.1.1.1

Medical condition in easily understood language

advanced metastatic breast cancer

cáncer de mama metastásico avanzado

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	LLT
E.1.2	Classification code	10072737
E.1.2	Term	Advanced breast cancer
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 determine whether treatment with ribociclib + fulvestrant prolongs progression free survival (PFS) compared to treatment with placebo + fulvestrant in postmenopausal women with HR+, HER2-negative breast cancer.

El objetivo principal es comparar la supervivencia libre de progresión (SLP) entre ribociclib en combinación con fulvestrant frente a placebo en combinación con fulvestrant en mujeres postmenopáusicas con cáncer de mama avanzado con HR+, HER2-negativo que no recibieron o que sólo recibieron un tratamiento previo endocrino para la enfermedad avanzada.

E.2.2

Secondary objectives of the trial

1. To determine whether treatment with ribociclib + fulvestrant prolongs overall survival (OS) compared to treatment with placebo + fulvestrant.
2. To evaluate the two treatment arms with respect to centrally assessed PFS
3. To evaluate the two treatment arms with respect to overall response rate (ORR), clinical benefit rate (CBR), time to response (TTR) and duration of response (DOR).
4. To evaluate the two treatment arms with respect to time to deterioration of ECOG performance status.
5. To evaluate the safety and tolerability of ribociclib in combination with fulvestrant.
6. To evaluate patient reported outcomes for health-related quality of life in the two treatment arms.
7. To characterize the pharmacokinetics (PK) of ribociclib (and relevant metabolites) when given in combination with fulvestrant.

?Comparar los dos brazos de tratamiento con respecto a la supervivencia global
?Evaluar los dos brazos de tratamiento con respecto a la SLP evaluada centralmente
?Evaluar los dos brazos de tratamiento con respecto a la tasa de respuesta global, tasa de beneficio clínico, tiempo hasta la respuesta y duración de la respuesta
?Evaluar los dos brazos de tratamiento con respecto al tiempo hasta el deterioro del estado funcional del ECOG
?Evaluar la tolerabilidad y la seguridad de ribociclib en combinación con fulvestrant,
?Evaluar los resultados notificados por la paciente cada 8 ó 12 semanas para la calidad de vida relacionada con la salud (QOL) en los dos brazos de tratamiento
?Caracterizar la farmacocinética (PK) de ribociclib (y de los metabolitos relevantes como LEQ803) el día 15 del ciclo 1, del día 1 del ciclo 2 y el día 15 del ciclo 2, cuando se administra en combinación con fulvestrant

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patient is postmenopausal.
2. Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory and has HER2-negative breast cancer.
3. Patient must have either measurable disease by RECIST 1.1 or at least one predominantly lytic bone lesion.
4. Patient has advanced (loco regionally recurrent not amenable to curative therapy or metastatic) breast cancer.
Patients may be:
? newly diagnosed advanced breast cancer, treatment naïve
? relapsed with documented evidence of progression more than 12 months from completion of (neo)adjuvant endocrine therapy with no treatment for metastatic disease
? relapsed with documented evidence of progression on or within 12 months from completion of (neo)adjuvant endocrine therapy with no treatment for metastatic disease
? relapsed with documented evidence of progression more than 12 months from completion of adjuvant endocrine therapy and then subsequently progressed with documented evidence of progression after one line of endocrine therapy (with either an antiestrogen or an aromatase inhibitor) for metastatic disease
? newly diagnosed advanced breast cancer, then relapsed with documented evidence of progression after one line of endocrine therapy (with either an antiestrogen or an aromatase inhibitor)
5. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
6. Patient has adequate bone marrow and organ function

?Pacientes adultas con ? 18 años en el momento del consentimiento informado y que hayan firmado el consentimiento informado antes de cualquier actividad relacionada con el ensayo y según las pautas locales
?La paciente deberá ser postmenopáusica
?Pacientes con un diagnóstico confirmado histológicamente y/o citológicamente de cáncer de mama con receptor estrogénico positivo y/o receptor progesterónico positivo
?Pacientes con cáncer de mama HER2 negativo
?Las pacientes deberán presentar:
- Enfermedad medible, es decir, por lo menos una lesión medible según los RECIST 1.1
- En caso de ausencia de enfermedad medible, entonces deberá estar presente por lo menos una lesión ósea predominantemente lítica
? Las pacientes pueden presentar:
- cáncer de mama avanzado de diagnóstico reciente, naïves a tratamiento
- recaída con evidencia documentada de progresión más de 12 meses desde la finalización de la terapia endocrina (neo)adyuvante sin tratamiento para la enfermedad metastásica
- recaída con evidencia documentada de progresión en o dentro de los 12 meses desde la finalización de la terapia endocrina (neo)adyuvante sin tratamiento para la enfermedad metastásica
- recaída con evidencia documentada de progresión más de 12 meses desde la finalización de la terapia endocrina (neo)adyuvante y que hayan progresado posteriormente con evidencia documentada de progresión después de una línea de terapia endocrina (con un antiestrógeno o un inhibidor de la aromatasa) para la enfermedad metastásica
- cáncer de mama avanzado de diagnóstico reciente, que recayeron posteriormente con evidencia documentada de progresión después de una línea de terapia endocrina (con un antiestrógeno o un inhibidor de la aromatasa)
?Pacientes con un estado funcional de 0 ó 1 del Grupo Oncológico Cooperativo del Este (ECOG)
?Pacientes con función orgánica y de la médula ósea adecuada

E.4

Principal exclusion criteria

1. Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator?s best judgment.
2. Patient has received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant or any CDK4/6 inhibitor.
3. Patient with inflammatory breast cancer at screening .
4. Patients with Child pugh scroe B or C
5. Patients has received prior neoadjuvant/adjuvant treatment with antracyclines at cumulative doses of 450mg/m² or more for doxorubicin or 900 mg/m² or more for epirubicin
6. Patient with CNS involvement unless they are at least 4 weeks from prior therapy completion to starting the study treatment and have stable CNS tumor at the time of screening and not receiving steroids and/or enzyme inducing anti-epileptic medications for brain metastases
7. Clinically significant, uncontrolled heart disease and/or recent cardiac events including any of the following:
? History of angina pectoris, symptomatic pericarditis, or myocardial infarction within 12 months prior to study entry
? History of documented congestive heart failure (New York Heart Association functional classification III-IV)
? Documented cardiomyopathy
? Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
? History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months.
? Congenital long QT syndrome or family history of long QT syndrome
? Systolic Blood Pressure (SBP) >160 or <90 mmHg
? Bradycardia (heart rate < 50 at rest), by ECG or pulse.
? On screening, inability to determine the QTcF interval on the ECG (ie: unreadable or not interpretable) or QTcF >450 msec (using Fridericia?s correction). All as determined by screening ECG (mean of triplicate ECGs).
8. Patient is currently receiving any of the following substances and cannot be discontinued 7 days prior to star the treatment:
? Known strong inducers or inhibitors of CYP3A4/5,
? That have a known risk to prolong the QT interval or induce Torsades de Pointes.
? Those have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5.
? Herbal preparations/medications, dietary supplements

?Pacientes con enfermedad visceral sintomática
?Pacientes que hayan recibido tratamiento previo con quimioterapia (excepto quimioterapia neoadyuvante/adyuvante), fulvestrant o cualquier inhibidor de CDK4/6.
?Pacientes con puntuación Child-Pugh B ó C
?Pacientes con cáncer de mama inflamatorio en la selección o enfermedad maligna concurrente o enfermedad maligna dentro de los 3 años de la aleatorización.
?Enfermedad cardíaca incontrolada y/o eventos cardíacos recientes clínicamente significativos, que incluya algo de lo siguiente:
- Antecedentes de angina de pecho, pericarditis sintomática o infarto de miocardio dentro de los 12 meses antes de la entrada en el estudio
- Antecedentes de insuficiencia cardíaca congestiva documentada (clasificación III-IV funcional de la Asociación de Cardiología de Nueva York)
- Cardiomiopatía documentada
- Pacientes con fracción de eyección ventricular izquierda (LVEF) < 50%, determinada con ventriculografía isotópica (MUGA) o ecocardiograma (ECO)
- Antecedentes de cualquier arritmia cardíaca, por ejemplo, arritmias ventriculares, supraventriculares, nodales o anomalías de conducción en los últimos 12 meses
- Síndrome de QT prolongado congénito o antecedentes familiares de síndrome QT prolongado
- Presión arterial sistólica (PAS) >160 o <90 mmHg
- Bradicardia (frecuencia cardíaca < 50 en reposo), con ECG o pulso.
- En la selección, imposibilidad de determinar el intervalo QTcF en el ECG (es decir: ilegible o no interpretable) o QTcF >450 ms (utilizando la corrección de Fridericia). Todo determinado con el ECG de selección (media de los ECGs triplicados).
?Pacientes que no se hayan recuperado de todas las toxicidades relacionadas con las terapias previas antineoplásicas a grado ?1 de la versión 4.03 de los CTCAE-NCI
?Pacientes que hayan recibido radioterapia ? 4 semanas o radiación de campo limitado para paliación ? 2 semanas antes de la aleatorización
?Pacientes con afectación del sistema nervioso central (SNC), excepto que cumplan TODOS los criterios siguientes:
?Por lo menos 4 semanas desde la finalización de la terapia previa (incluyendo radiación y/o cirugía) hasta el inicio del estudio
- Tumor del SNC clínicamente estable en el momento de la selección y que no reciban esteroides y/o medicaciones antiepilépticas inductoras de enzimas para las metástasis cerebrales
- Pacientes con cualquier otra condición médica concomitante grave y/o incontrolada que pudiesen, a juicio del investigador, causar riesgos de seguridad inaceptables, contraindicar la participación de la paciente en el estudio clínico o comprometer el cumplimiento con el protocolo.
? Pacientes que actualmente estén recibiendo alguna de las siguientes sustancias y que no puedan suspenderlas 7 días antes de iniciar el tratamiento:
?Inhibidores o inductores potentes conocidos de CYP3A4/5.
? Que posean un riesgo conocido de prolongar el intervalo QT o de inducir Torsades de Pointes.
?Que posean un estrecho índice terapéutico y que sean metabolizados predominantemente por CYP3A4/5
?Preparaciones/medicaciones herbales, suplementos dietéticos.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of the study is PFS, defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS will be assessed according to RECIST 1.1.

El objetivo primario del estudio es la SSP, que se define como el tiempo desde la fecha de la aleatorización hasta la fecha de la primera progresión documentada o muerte por cualquier causa. PFS se evaluará de acuerdo con RECIST 1.1.

E.5.1.1

Timepoint(s) of evaluation of this end point

final analysis around 26 months from the date of first patient randomized

análisis final alrededor de 26 meses desde la fecha de la primera paciente aleatorizada

E.5.2

Secondary end point(s)

1. Overall survival: Time from date of randomization to the date of death from any cause.
2. PFS per blinded independent review committee (BIRC) and RECIST 1.1 criteria
3. ORR: Proportion of patients with best overall response (BOR) of complete response (CR) or partial response (PR) according to RECIST 1.1.
4. CBR: Percentage of patients with complete response (CR) or partial response (PR) or stable disease (SD) lasting 24 weeks or longer as defined in RECIST 1.1
5. TTR: Time from randomization to the first documented and confirmed response (complete response or partial response) as defined in RECIST 1.1
6. DOR: Time from the first documented response (CR or PR) to the first documented progression or death due to underlying cancer as defined in RECIST 1.1
7. ECOG: Time to definitive deterioration of ECOG performance status from baseline: Time to deterioration of ECOG performance Status.
8. Safety and tolerability of LEE001: Determined by type, frequency and severity of Adverse Events per CTCAE version 4.03 and type, frequency and severity of laboratory toxicities per CTCAE version 4.03
9. Time to 10% deterioration in the global health status/QOL scale score of the EORTC QLQ-C30: Patient reported outcomes for health related quality of life
10. A change from baseline in the global health status/QOL scale score of the EORTC QLQ-C30: Patient reported outcomes for health related quality of life
11. Summary statistics for PK parameters at steady state, including but not limited to Cmax, Tmax, Ctrough for ribociclib (and relevant metabolites)

1. supervivencia global: Tiempo desde la fecha de la aleatorización hasta la fecha de muerte por cualquier causa.
2. PFS por comité de revisión independiente cegado (BIRC) y RECIST 1.1 criterios
3. TRG: Proporción de pacientes con mejor respuesta global (BOR) de respuesta completa (CR) o respuesta parcial (PR) de acuerdo con RECIST 1.1.
4. CBR: Porcentaje de pacientes con respuesta completa (CR) o respuesta parcial (RP) o enfermedad estable (SD) que dura 24 semanas o más según se define en RECIST 1.1
5. TTR: Tiempo desde la aleatorización hasta la primera documentada y respuesta (respuesta completa o respuesta parcial) confirmada como se define en RECIST 1.1
6. DOR: Tiempo de la primera respuesta documentada (CR o PR) a la primera progresión documentada o muerte debido a cáncer subyacente como se define en los criterios RECIST 1.1
7. ECOG: Tiempo al deterioro definitivo del estado funcional ECOG de línea de base: la hora de deterioro del estado funcional ECOG.
8. La seguridad y tolerabilidad de LEE001: Determinado por tipo, frecuencia y gravedad de los eventos adversos por CTCAE versión 4.03 y el tipo, la frecuencia y severidad de las toxicidades de laboratorio por CTCAE versión 4.03
9. Tiempo a 10% el deterioro en la puntuación de la escala estado de salud / calidad de vida global de la EORTC QLQ-C30: la Paciente informó los resultados de calidad relacionada con la salud de la vida
10. Un cambio desde el inicio en la puntuación de la escala estado global de salud / calidad de vida de la EORTC QLQ-C30: la Paciente informó de los resultados de calidad relacionada con la salud de la vida

E.5.2.1

Timepoint(s) of evaluation of this end point

1. 58 months from date of first patient randomized.
2. PFS per BIRC: up to approximately 26 months
3. ORR: up to approximately 26 months
4. CBR: up to approximately 26 months
5. TTR: up to approximately 26 months
6. DOR: up to approximately 26 months
7. ECOG performance status deterioration: up to approximately 26 months
8. safety and tolerability: up to approximately 26 months
9. 10% deterioration in QOL: up to approximately 26 months
10. change from baseline in QOL: up to approximately 26 months
11. summary statistics for PK parameters: up to approximately 26 month

1. 58 meses desde la fecha de la primera paciente aleatorizados.
2. PFS por BIRC: hasta aproximadamente 26 meses
3. TRG: hasta aproximadamente 26 meses
4. CBR: hasta aproximadamente 26 meses
5. TTR: hasta aproximadamente 26 meses
6. DOR: hasta aproximadamente 26 meses
7. ECOG performance status deterioro: hasta aproximadamente 26 meses
8. seguridad y tolerabilidad: hasta aproximadamente 26 meses
9. 10% el deterioro en la calidad de vida: hasta aproximadamente 26 meses
10. El cambio de línea de base en la calidad de vida: hasta aproximadamente 26 meses
11. estadísticos de resumen para los parámetros farmacocinéticos: hasta aproximadamente 26 meses

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

Yes

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

Quality of Life (QoL)

Cuestionarios de calidad de Vida

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

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

146

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

Argentina

Australia

Austria

Belgium

Brazil

Canada

China

Colombia

Czech Republic

Denmark

France

Germany

Hong Kong

Hungary

India

Israel

Italy

Korea, Republic of

Lebanon

Malaysia

Mexico

Netherlands

Norway

Poland

Portugal

Russian Federation

Saudi Arabia

Singapore

South Africa

Spain

Sweden

Switzerland

Taiwan

Thailand

Turkey

United Kingdom

United States

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

The end of the study for a given patient is defined as when the patient permanently
discontinues study treatment with ribociclib + fulvestrant or placebo + fulvestrant and all the end of trial procedures are completed.

El final del estudio para un paciente dado se define como cuando el paciente permanentemente discontinúa el tratamiento del estudio con ribociclib + fulvestrant o placebo + fulvestrant y se ha completado el final de los procedimientos del estudio.

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:

396

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

264

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

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.4.2

For a multinational trial

F.4.2.1

In the EEA

289

F.4.2.2

In the whole clinical trial

660

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)

Patients continuing to derive benefit from study treatment at the end of the study in the opinion of the investigator will be able to continue receiving trial therapy on a separate protocol. Alternatively Novartis will provide study treatment to the investigator as per local regulations.

Las pacientes que continúan pueden obtener beneficios de tratamiento del estudio al final del estudio, en opinión del investigador podrán seguir recibiendo la terapia del ensayo en un protocolo separado. Alternativamente Novartis proporcionará tratamiento del estudio para el investigador como por las regulaciones locales.

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

2015-06-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-06-15

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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