Clinical Trials Register

Summary
EudraCT Number:	2014-003185-25
Sponsor's Protocol Code Number:	GO29058
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:	2015-02-09
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

2014-003185-25

A.3

Full title of the trial

A PHASE III, DOUBLE-BLIND, PLACEBO CONTROLLED, RANDOMIZED STUDY OF TASELISIB PLUS FULVESTRANT VERSUS PLACEBO PLUS FULVESTRANT IN POSTMENOPAUSAL WOMEN WITH ESTROGEN RECEPTOR POSITIVE AND HER2 NEGATIVE LOCALLY ADVANCED OR METASTATIC BREAST CANCER WHO HAVE DISEASE RECURRRENCE OR PROGRESSION DURING OR AFTER AROMATASE INHIBITOR THERAPY

ESTUDIO DE FASE III, DOBLE CIEGO, CONTROLADO CON PLACEBO, ALEATORIZADO, DE TASELISIB MÁS FULVESTRANT FRENTE A PLACEBO MÁS FULVESTRANT EN MUJERES POSMENOPÁUSICAS CON CÁNCER DE MAMA RECEPTOR DE ESTRÓGENO POSITIVO Y HER2 NEGATIVO, LOCALMENTE AVANZADO O METASTÁSICO, QUE HAN PRESENTADO RECIDIVA O PROGRESIÓN DE LA ENFERMEDAD DURANTE 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 Study Of Taselisib + Fulvestrant Versus Placebo + Fulvestrant In Patients With Advanced or Metastatic Breast Cancer Who Have Disease Recurrence or Progression during or After Aromatase Inhibitor Therapy

Estudio de Taselisib+Fulvestrant frente a Placebo+Fulvestrant en pacientes con cáncer de mama avanzado o mestásico que han presentado recidiva o progresión de la enfermedad durante o después del tratamiento con un inhibidor de la aromatasa.

A.4.1

Sponsor's protocol code number

GO29058

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	Roche Farma, S.A., en nombre de F. Hoffmann- La Roche Ltd.
B.1.3.4	Country	Switzerland
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	F. Hoffmann-La Roche Ltd
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	F. Hoffmann-La Roche Ltd
B.5.2	Functional name of contact point	Trial Information Support Line-TISL
B.5.3	Address:
B.5.3.1	Street Address	Grenzacherstrasse 124
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4070
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+34913257300
B.5.6	E-mail	global.rochegenentechtrials@roche.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	GDC-0032
D.3.2	Product code	RO 553-7381/F12
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	Taselisib
D.3.9.2	Current sponsor code	GDC-0032
D.3.9.3	Other descriptive name	RO5537381
D.3.9.4	EV Substance Code	SUB61505
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	2
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.3.4	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.3.9.4	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.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	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

WOMEN WITH ER-POSITIVE AND HER2-NEGATIVE, LOCALLY ADVANCED OR METASTATIC BREAST CANCER WHO HAS DIDEASE RECURRENCE OR PROGRESSION DURING OR AFTER AROMATASE INHIBITOR THERAPY

Mujeres con cáncer de mama irrresecable locamente avanzado Re+ y Her2-negativo que han presentado recidiva o progresión de la enfermedad durante o después del tratamiento con un inhibidor de la aromatasa.

E.1.1.1

Medical condition in easily understood language

Advanced or metastatic breast cancer that is positive for the estrogen receptor and negative for the HER2 receptor and has recurred or progressed on or after aromatase inhibitor therapy

Cáncer de mama avanzado o metastásico positivo para receptor de estrógeno y negativo para receptor de Her2 que ha presentado recidiva o progresión durante o tras terapia con inhibidor de la aromatasa

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	17.1
E.1.2	Level	LLT
E.1.2	Classification code	10070575
E.1.2	Term	Estrogen receptor positive 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

The primary objective of this study is to compare the efficacy between taselisib plus fulvestrant versus placebo plus fulvestrant as measured by investigator-assessed progression-free survival (PFS) in patients with PIK3CA mutant tumors

El objetivo principal de este estudio es comparar la eficacia de taselisib + fulvestrant frente a placebo + fulvestrant, determinada por la supervivencia libre de progresión (SLP) evaluada por el investigador en pacientes con tumores con mutación de PIK3CA.

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are the following:
?To evaluate the safety of taselisib plus fulvestrant versus placebo plus fulvestrant.
?To compare the efficacy between taselisib plus fulvestrant versus placebo plus fulvestrant as measured by OS in patients with PIK3CA mutant tumors.
?To compare the overall objective response rate (ORR) and clinical benefit rate (CBR), and estimate the duration of response (DOR) between taselisib plus fulvestrant versus placebo plus fulvestrant in patients with PIK3CA mutant tumors, based on investigator assessment.

Los objetivos secundarios de este estudio son:
- Evaluar la seguridad de taselisib + fulvestrant frente a placebo + fulvestrant.
- Comparar la eficacia de taselisib + fulvestrant frente a placebo + fulvestrant, determinada por la supervivencia global (SG) valorada por el investigador en pacientes con tumores con mutación de PIK3CA.
- Comparar la tasa de respuesta objetiva (TRO) total y la TBC de taselisib, y calcular la duración de la respuesta objetiva (DRO) de taselisib + fulvestrant frente a placebo + fulvestrant en pacientes con tumores con mutación de PIK3CA basándose en las evaluaciones tumorales realizadas por el investigador.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Postmenopausal women with histologically or cytologically confirmed locally advanced or metastatic estrogen-receptor positive (ER+) breast cancer
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Endocrine therapy (e.g., fulvestrant) is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study
- Radiologic/objective evidence of recurrence or progression to the most recent systemic therapy for breast cancer
- Recurrence or progression during or after aromatase inhibitor
- Evaluable or measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- Consent to provide tumor tissue (block or a minimum of 20 slides) from the most recent tumor tissue for PIK3CA-mutation testing; a valid cobas PIK3CA mutation result by central testing is required
- Adequate hematologic and end-organ function within 28 days prior to treatment initiation

- Mujeres postmenopáusicas con cáncer de mama invasivo RE+ confirmado histológica o citológicamente: cáncer de mama metastásico o localmente avanzado.
- Estado funcional del ECOG de 0 ó 1.
- Está recomendado tratamiento endocrino (p. ej., fulvestrant) y no está indicada la quimioterapia citotóxica en el momento de entrar en el estudio.
- Pruebas radiológicas/objetivas de recidiva o progresión con el tratamiento sistémico más reciente del cáncer de mama.
- Pruebas radiológicas/objetivas de recidiva o progresión durante o después de Inhibidor de la aromatasa.
- Enfermedad evaluable o medible mediante los RECIST v1.1.
- Consentimiento para proporcionar tejido tumoral (bloque o un mínimo de 20 laminillas) procedentes del tejido tumoral disponible obtenido en la fecha más reciente para pruebas de la mutación de PIK3CA; se necesita un resultado de la mutación de PIK3CA de cobas analizado centralmente.
- Función hematológica y de órganos diana adecuada en los 28 días previos al día 1 del ciclo 1.

E.4

Principal exclusion criteria

- HER2-positive disease by local laboratory testing (immunohistochemistry [IHC] 3+ staining or in situ hybridization positive)
- Prior treatment with fulvestrant
- Prior treatment with a PI3K inhibitor, mTOR inhibitor (e.g. everolimus), or AKT inhibitor
- Prior anti-cancer therapy within 2 weeks prior to Day 1 of Cycle 1
- Prior radiation therapy within 2 weeks prior to Day 1 of Cycle 1
- All acute treatment-related toxicity must have resolved to Grade </= 1 or be deemed stable by the Investigator
- Prior treatment with > 1 cytotoxic chemotherapy regimen for metastatic breast cancer
- Concurrent hormone replacement therapy
- Known untreated or active central nervous system (CNS) metastases
- Type 1 or Type 2 diabetes mellitus requiring anti-hyperglycemic medications
- History of inflammatory bowel disease or active bowel inflammation
- Clinically significant cardiac or pulmonary dysfunction
- Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with HIV, hepatitis B virus or C

- Enfermedad positiva para HER2 en las pruebas analíticas locales (tinción IHQ 3+ o hibridación in situ positiva).
-Tratamiento previo con fulvestrant.
-Tratamiento previo con un inhibidor de PI3K, mTOR (como everolimus) o AKT.
-Tratamiento previo contra el cáncer en las 2 semanas anteriores al día 1 del ciclo 1.
-Radioterapia previa en las 2 semanas anteriores al día 1 del ciclo 1.
-Toda toxicidad aguda relacionada con el tratamiento deberá haberse resuelto a un grado ? 1 o ser considerada estable por el investigador.
-Tratamiento previo del CMM con > 1 régimen de quimioterapia citotóxico.
-Tratamiento de sustitución hormonal concomitante
-Metástasis en el SNC conocidas, no tratadas o activas
-Diabetes mellitus de tipo 1 ó 2 que precise medicación hipoglucemiante.
- Antecedentes de enfermedad inflamatoria intestinal o Inflamación intestinal activa.
-Disfunción cardíaca o pulmonar de importancia clínica.
-Antecedentes de importancia clínica de enfermedad hepática, incluida cirrosis, abuso de alcohol actual o infección activa conocida con el VIH, o con los virus de la hepatitis B (VHB) o de la hepatitis C (VHC).

E.5 End points

E.5.1

Primary end point(s)

Progression-free survival (PFS), as determined by the investigator with the use of RECIST version 1.1

La Supervivencia Libre de Progresión, determinada por el investigador utilizando los criterios de evaluación de respuesta en tumores sólidos (Response Evaluation Criteria in Solid Tumors - RECIST) v1.1.

E.5.1.1

Timepoint(s) of evaluation of this end point

Up to approximately 3.5 years

Hasta aproximadamente 3.5 años.

E.5.2

Secondary end point(s)

1. Overall survival
2. Overall objective response (partial response [PR] plus complete response [CR]), as determined by using RECIST v.1.1
3. Clinical benefit, defined as objective response (PR+CR), or stable disease (SD) lasting for at least 24 weeks since randomization
4. Duration of objective response
5. Incidence of adverse events, according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03

1. Supervivencia Global.
2. Tasa de respuesta objetiva (Respuesta parcial (RP) + respuesta completa (RC)), determinada mediante los RECIST v1.1.
3. Beneficio clínico, definido como respuesta objetiva (RP+RC) o EE de ? 24 semanas de duración desde la aleatorización.
4. Duración de respuesta objetiva.
5. La incidencia de los acontecimientos adversos, según la versión 4.0 de los criterios terminológicos comunes para acontecimientos adversos del National Cancer Institute [National Cancer Institute Common Terminology Criteria for Adverse Events - CTCAE del NCI v4.0]).

E.5.2.1

Timepoint(s) of evaluation of this end point

1 to 5. Up to approximately 3.5 years

1 a 5: Hasta aproximadamente 3.5 años.

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

Yes

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

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

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

Australia

Austria

Bulgaria

Canada

Colombia

Czech Republic

France

Germany

Greece

Italy

Japan

Korea, Republic of

Mexico

Netherlands

Peru

Poland

Portugal

Romania

Russian Federation

Spain

Sweden

Turkey

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 study will be considered completed when approximately 330 deaths in patients with PIK3CA mutant tumors have been reported and the final analysis of overall survival is completed or when the Sponsor decides to stop the study.

Se considerará finalizado el estudio cuando se hayan notificado alrededor de 330 fallecimientos de pacientes con tumores con mutación de PIK3CA y se haya completado el análisis final de la SG, o cuando el promotor decida interrumpir el 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

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:

390

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

210

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

311

F.4.2.2

In the whole clinical trial

600

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)

Currently, the Sponsor does not have any plans to provide taselisib or any other study treatments or interventions after the end of the study or for any patient who has discontinued or withdrawn from the study. Crossover from the control arm to the taselisib arm is not allowed. The Sponsor will evaluate whether to continue providing taselisib after the main study is over in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product.

Actualmente, el promotor no tiene ningún plan para proporcionar el taselisib ni ningún otro tratamiento o intervenciones del estudio después del final del estudio ni a ninguna paciente que haya discontinuado o se haya retirado del estudio. No se permite el cruce del grupo de control al del taselisib. El promotor evaluará si sigue suministrando taselisib después del final del estudio principal de acuerdo con la política global de Roche sobre el acceso continuado al medicamento en investigación.

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

2015-02-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-01-09

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-06-29

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