Clinical Trials Register

Summary
EudraCT Number:	2015-000340-42
Sponsor's Protocol Code Number:	CBYL719C2301
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:	2015-07-31
Trial 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

2015-000340-42

A.3

Full title of the trial

SOLAR-1: A phase III randomized double-blind, placebo controlled study of alpelisib in combination with fulvestrant for postmenopausal women with hormone receptor positive, HER2-negative advanced breast cancer which progressed on or after aromatase inhibitor treatment

SOLAR-1: Estudio de fase III, aleatorizado, doble ciego, controlado con placebo, de alpelisib en combinación con fulvestrant en hombres y mujeres posmenopáusicas con cáncer de mama avanzado, receptor hormonal positivo, HER2 negativo que han progresado mientras o después del tratamiento con un inhibidor de la aromatasa

A.3.1

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

A clinical study to investigate the therapeutic benefit and safety of combining alpelisib and fulvestrant in the treatment of postmenopausal women with advanced breast cancer whose disease came back while on or after treatment with an aromatase inhibitor

Estudio que evalúa la eficacia y seguridad de alpelisib más fulvestrant en hombres y mujeres posmenopáusicas con cáncer de mama avanzado que han progresado mientras o después del tratamiento con un IA.

A.3.2

Name or abbreviated title of the trial where available

SOLAR-1

A.4.1

Sponsor's protocol code number

CBYL719C2301

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.3.1	Product name	Alpelisib
D.3.2	Product code	BYL719
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	Alpelisib
D.3.9.1	CAS number	1217486-61-7
D.3.9.2	Current sponsor code	BYL719
D.3.9.3	Other descriptive name	BYL719
D.3.9.4	EV Substance Code	SUB31405
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	50
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.2.1.1.1	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	Faslodex
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.3.9.3	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	50
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	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	Alpelisib
D.3.2	Product code	BYL719
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	Alpelisib
D.3.9.1	CAS number	1217486-61-7
D.3.9.2	Current sponsor code	BYL719
D.3.9.3	Other descriptive name	BYL719
D.3.9.4	EV Substance Code	SUB31405
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.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	Film-coated tablet
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

Hormone receptor positive, HER2-negative advanced breast cancer

Cáncer de mama avanzado, receptor hormonal positivo, HER2 negativo

E.1.1.1

Medical condition in easily understood language

Advanced breast cancer that is distinguished from other breast cancer types by stage and the presence of molecules that respond to certain hormones

Cáncer de mama avanzado que se distingue de otros tipos de cáncer de mama por el grado y por la presencia de moléculas que responden a ciertas hormonas

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 alpelisib in combination with fulvestrant prolongs PFS compared to treatment with placebo in combination with fulvestrant for each of the following cohorts i) patients with PIK3CA mutant status ii) patients with PIK3CA non-mutant status

Determinar si el tratamiento con alpelisib en combinación con fulvestrant prolonga la SLP en comparación con el tratamiento con placebo en combinación con fulvestrant en base a la evaluación radiológica local para cada una de las siguientes cohortes
i) pacientes con PIK3CA mutado
ii) pacientes con PIK3CA no mutado

E.2.2

Secondary objectives of the trial

To determine whether treatment with alpelisib in combination with fulvestrant prolongs overall survival (OS) compared to treatment with placebo in combination with fulvestrant for each of the following cohorts i) patients with PIK3CA mutant status ii) patients with PIK3CA non-mutant status

To evaluate the two treatment arms and cohorts of interest with respect to centrally assessed PFS, overall response rate (ORR) and clinical benefit rate

Further secondary objectives and details are described in the protocol

Determinar si el tratamiento con alpelisib en combinación con fulvestrant prolonga la supervivencia global (SG) en comparación con el tratamiento con placebo en combinación con fulvestrant para cada una de las siguientes cohortes
i) pacientes con PIK3CA mutado
ii) pacientes con PIK3CA no mutado

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patient is an adult ? 18 years old at the time of informed consent
2. Patient has adequate FFPE tumor tissue for the analysis of PIK3CA mutational status
3. Patient has identified PIK3CA status
4. If female, then the patient is postmenopausal
5. Patient has radiological or objective evidence of recurrence or progression
6. Patient has a histologically and/or cytologically confirmed diagnosis of ER+ and/or PgR+ breast cancer
7. Patient has HER2-negative breast cancer
8. Patient has either measurable disease (at least one measurable lesion as per RECIST 1.1) or at least one predominantly lytic bone lesion
9. Patient has advanced (loco regionally recurrent not amenable to curative therapy or metastatic) breast cancer
10. Patient has recurrence or progression of disease during or after AI therapy (i.e. letrozole, anastrozole, exemestane)

Further inclusion criteria and details are described in the protocol

1. El paciente es un adulto ? 18 años de edad en el momento del consentimiento informado y ha firmado el consentimiento informado antes de realizar ninguna de las actividades relacionadas con el ensayo y de acuerdo con las guías locales.
2. Se dispone de tejido tumoral FFPE adecuado del paciente para que el laboratorio designado por Novartis analice el estado de mutación PIK3CA. Se requiere un bloque de tumor (preferido) o entre 15 y 20 cortes (15 cortes como mínimo de una muestra quirúrgica, 20 cortes como mínimo de una biopsia).
3. Paciente con estado de PIK3CA identificado (mutado o no mutado; determinado por un laboratorio designado por Novartis en la muestra o corte FFPE).
4. Si es mujer, entonces la paciente es posmenopáusica.
5. El paciente tiene evidencia radiológica u objetiva de recurrencia o progresión.
6. Paciente con diagnóstico histológicamente y/o citológicamente confirmado de cáncer de mama ER+ y/o PgR+ por el laboratorio local.
7. Paciente con cáncer de mama HER2-negativo definido como prueba de hibridización in situ o estado IHC de 0, 1+ o 2+. Si la IHC es 2+, se requiere una prueba negativa de hibridización in situ (FISH, CISH, o SISH) realizada por el laboratorio local.
8. El paciente tiene o bien:
? Enfermedad medible, es decir, al menos una lesión medible según los criterios RECIST 1.1 (una lesión en un lugar previamente irradiado sólo puede contabilizarse como una lesión diana si existe un claro signo de progresión desde la radiación ) O
? Si no hay enfermedad medible, en tal caso deberá observarse al menos una lesión ósea predominantemente lítica (los pacientes sin ninguna enfermedad medible y con sólo una lesión ósea predominantemente lítica que ha sido previamente irradiada son elegibles si existe evidencia documentada de progresión de la enfermedad de la lesión ósea después de la radiación).
9. Paciente con cáncer de mama avanzado (recurrente locorregionalmente no candidato a terapia curativa o metastásico).
10. Paciente con recaída o progresión de la enfermedad durante o después de terapia con IA (p. ej., letrozol, anastrozol, exemestano).

En el protocolo se describen más criterios de inclusión y más detalles.

E.4

Principal exclusion criteria

1. Patient with symptomatic visceral disease or any prohibitive disease burden
2. Patient has received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, any PI3K, mTOR or AKT inhibitor
3. Patient has a known hypersensitivity to any of the excipients of alpelisib or fulvestrant
4. Patient with inflammatory breast cancer at screening
5. Patient is concurrently using other anti-cancer therapy
6. Patient has had surgery within 14 days prior to starting study drug or has not recovered from major side effects
7. Patient has not recovered from all toxicities related to prior anticancer therapies except alopecia

Further exclusion criteria and details are described in the protocol

1. Paciente con enfermedad visceral sintomática o cualquier situación patológica que hagan que el paciente no sea elegible para terapia endocrina según el mejor criterio del investigador
2. El paciente ha recibido tratamiento previo con quimioterapia (excepto quimioterapia neoadyuvante/ adyuvante), fulvestrant, cualquier inhibidor PI3K, mTOR o AKT
3. El paciente tiene hipersensibilidad conocida a alpelisib o fulvestrant, o a cualquiera de los excipientes de alpelisib o fulvestrant.
4. Paciente con cáncer de mama inflamatorio en la selección.
5. El paciente está recibiendo concurrentemente otra terapia antineoplásica.
6. El paciente ha sido sometido a cirugía en los 14 días previos al inicio de la medicación del estudio o no se ha recuperado de efectos secundarios importantes.
7. El paciente no se ha recuperado de todas las toxicidades relacionadas con terapias antineoplásicas previas a Grado ?1 de los CTCAE del NCI versión 4.03. Excepto por este criterio: los pacientes con cualquier grado de alopecia podrán ser incluidos en el estudio.

E.5 End points

E.5.1

Primary end point(s)

Determinar si el tratamiento con alpelisib en combinación con fulvestrant prolonga la SLP comparado con el tratamiento con placebo en combinación con fulvestrant para cada una de las siguientes cohortes i) pacientes con PIK3CA mutado ii) pacientes con PIK3CA no mutado

E.5.1.1

Timepoint(s) of evaluation of this end point

Patients with PIK3CA mutant status: 38 months
Patients with PIK3CA non-mutant status: 28 months

pacientes con PIK3CA mutado: 38 meses
pacientes con PIK3CA no mutado: 28 meses

E.5.2

Secondary end point(s)

Determinar si el tratamiento con alpelisib en combinación con fulvestrant prolonga la supervivencia global (SG) comparado con el tratamiento con placebo en combinación con fulvestrant para cada una de las siguientes cohortes i) pacientes con PIK3CA mutado ii) pacientes con PIK3CA no mutado

E.5.2.1

Timepoint(s) of evaluation of this end point

59 months

59 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

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

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

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

120

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

Bulgaria

Canada

Chile

Colombia

Czech Republic

Denmark

France

Germany

Hong Kong

India

Israel

Italy

Japan

Korea, Republic of

Lebanon

Mexico

Netherlands

Norway

Peru

Portugal

Russian Federation

Singapore

Spain

Sweden

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 overall study is defined as the time point when data collection will stop in both cohorts and the final analysis of the study will occur.

El final del estudio en su conjunto se define como el momento en que la recogida de datos se interrumpirá en ambas cohortes y tendrá lugar el análisis final 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:

246

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

574

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.4.2

For a multinational trial

F.4.2.1

In the EEA

300

F.4.2.2

In the whole clinical trial

820

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)

After discontinuing all study treatment, further treatment is left to the physician?s discretion.

Después de interrumpir todo el tratamiento del estudio, el tratamiento adicional se deja a criterio del médico.

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

2015-09-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-08-04

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

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