Clinical Trials Register

Summary
EudraCT Number:	2015-000106-19
Sponsor's Protocol Code Number:	GO29689
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:	2015-09-11
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

2015-000106-19

A.3

Full title of the trial

A PHASE II, OPEN-LABEL, RANDOMIZED STUDY OF GDC-0810 VERSUS FULVESTRANT IN POSTMENOPAUSAL WOMEN WITH ADVANCED OR METASTATIC ER+/HER2- BREAST CANCER RESISTANT TO AROMATASE INHIBITOR THERAPY

ESTUDIO DE FASE II, ABIERTO, ALEATORIZADO DE GDC 0810 FRENTE A FULVESTRANT EN MUJERES POSTMENOPÁUSICAS CON CÁNCER DE MAMA AVANZADO O METASTÁSICO ER+/HER2- RESISTENTE A TERAPIA INHIBIDORA DE LA AROMATASA

A.3.1

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

A Study of GDC-0810 versus Fulvestrant in Postmenopausal Women with Advanced or Metastatic ER+/HER2- Breast Cancer Resistant To Aromatase Inhibitor Therapy

Estudio de GDC-0810 frente a fulvesntrant en mujeres postmenopáusicas con cáncer de mama avanzado o metastásico ER+/Her- resistente a terapia inhibidora de la aromatasa.

A.4.1

Sponsor's protocol code number

GO29689

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	Genentech, Inc
B.1.3.4	Country	United States
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	Genentech Inc. c/o F. Hoffmann-La Roche Ltd
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Genentech Inc. c/o 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	+34 91 325 73 00
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-0810
D.3.2	Product code	705-6118/F01-01
D.3.4	Pharmaceutical form	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	N/A
D.3.9.1	CAS number	N/A
D.3.9.2	Current sponsor code	GDC-0810 (RO7056118)
D.3.9.3	Other descriptive name	RO7056118
D.3.9.4	EV Substance Code	SUB171190
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	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.3.4	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.3.9.3	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.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

Advanced or Metastatic ER+/HER2- Breast Cancer

Cáncer de mama avanzado o metastásico ER+/HER2-

E.1.1.1

Medical condition in easily understood language

Breast cancer that has spread beyond the breast tissue and surrounding lymph nodes and tests positive for estrogen receptors and negative for human epidermal growth factor receptor-2

Cáncer de mama que se ha extendido más alla del tejido de la mama y gáglios linfáticos circundantes y resultado positivo en test para receptores de estrógenos y negativo Her2.

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	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

? To evaluate the efficacy of GDC-0810 compared with fulvestrant in the intent to treat (ITT) population as measured by progression free survival (PFS)
? To evaluate the efficacy of GDC-0810 compared with fulvestrant in the estrogen receptor 1 (ESR1) mutant population as measured by PFS

- Evaluar la eficacia de GDC-0810 en comparación con fulvestrant en la población con intención de tratar (IDT) medida según la supervivencia sin progresión (SSP).
- Evaluar la eficacia de GDC-0810 en comparación con fulvestrant en la población con mutaciones detectables en el ESR1 medida según la SSP

E.2.2

Secondary objectives of the trial

? To assess the clinical activity of GDC-0810 versus fulvestrant, as measured by objective response rate (ORR), duration of response (DOR), clinical benefit rate (CBR), and overall survival (OS)
? To evaluate the safety and tolerability of GDC-0810 compared with fulvestrant, focusing on the nature, frequency, and severity of serious and non-serious adverse events
? To assess the pharmacokinetics of GDC-0810 in patients with advanced or metastatic breast cancer (MBC) resistant to aromatase inhibitor (AI) therapy

- Evaluar la actividad clínica de GDC-0810 frente a fulvestrant, medida según la tasa de respuesta objetiva (TRO), la duración de la respuesta objetiva (DRO), la tasa de beneficio clínico (TBC) y la supervivencia global (SG).
- Evaluar la seguridad y la tolerabilidad de GDC-0810 en comparación con fulvestrant, con especial atención en la naturaleza, la frecuencia y la gravedad de los acontecimientos adversos graves y no graves.
- Evaluar la farmacocinética de GDC-0810 en pacientes con cáncer de mama avanzado o metastásico resistente al tratamiento con inhibidor de la aromatasa (IA).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Postmenopausal women with histologically or cytologically confirmed invasive, estrogen receptor positive (ER+)/ human epidermal growth factor receptor 2 negative (HER2-) (defined by local guidelines) metastatic or inoperable (not amenable to resection or other local therapy with curative intent), locally advanced breast cancer
- Patients for whom endocrine therapy (e.g., fulvestrant) is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study, as per national or local treatment guidelines
- Radiologic/objective evidence of recurrence or progression to the most recent systemic therapy for breast cancer
- Radiologic/objective evidence of breast cancer recurrence or progression while on or within 6 months after the end of adjuvant treatment with an AI, or progression while on or within 1 month after the end of prior AI treatment for locally advanced or MBC
- Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or non-measurable, evaluable disease with at least one evaluable bone lesion by RECIST v1.1 based on radiologic scans within 28 days of Day 1 of Cycle 1
- Eastern Cooperative Oncology Group Performance Status of 0 or 1
- Adequate hematologic and end-organ function

- Mujeres posmenopáusicas con cáncer de mama ER + /HER2- (definido según las directrices locales) metastásico o irresecable (no se puede extirpar ni intentar curar con cualquier otro tratamiento local), invasivo o localmente avanzado y diagnosticado de forma citológica o histológica.
- Pacientes a las que se recomienda el tratamiento endrocrino (p. ej., fulvestrant) y para las que no está indicado el tratamiento con quimioterapia citotóxica en el momento del acceso al estudio, según las directrices del tratamiento locales y nacionales.
- Pruebas objetivas/radiológicas de recurrencia o progresión hasta el tratamiento generalizado más reciente para el cáncer de mama.
- Pruebas objetivas/radiológicas de recurrencia o progresión del cáncer de mama durante el tratamiento complementario con un IA o en un período posterior de 6 meses tras la finalización de este, o bien progresión durante el tratamiento con IA anterior para cáncer de mama localmente avanzado o metastásico o en un período posterior de 1 mes tras la finalización de este.
- Las pacientes deben tener una enfermedad mensurable según el sistema RECIST versión 1.1 o inmensurable, enfermedad evaluable con al menos una lesión ósea evaluable según RECIST versión 1.1 en función de las exploraciones radiológicas realizadas en el plazo de 28 días del día 1 del ciclo 1.
- Niveles de calidad de vida de 0 o 1 de ECOG
- Actividad suficiente hematológica y del órgano terminal

E.4

Principal exclusion criteria

- HER2 positive disease (immunohistochemistry [IHC] 3+ staining, fluorescence in situ hybridization [FISH] positive, and/or chromogenic in situ hybridization [CISH] positive)
- Prior treatment with fulvestrant
- Prior anti-cancer therapy within 2 weeks prior to Cycle 1 Day 1
- Prior radiation therapy within 2 weeks prior to Cycle 1 Day 1
- Prior treatment with >1 cytotoxic chemotherapy regimens or >2 endocrine therapies for advanced or metastatic disease
- Ongoing, acute treatment-related toxicity that has not resolved to Grade <=1 or been deemed stable by the investigator
- Concurrent hormone replacement therapy
- Known untreated or active central nervous system metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control)
- History of other malignancy within the previous 5 years
- Inability or unwillingness to swallow pills or receive intramuscular injections
- Clinically significant cardiac or pulmonary dysfunction
- Major surgical procedure or significant traumatic injury within 28 days prior to Day 1 of Cycle 1 or anticipation of the need for major surgery during the course of study treatment

- Cáncer HER2 positivo (tinción inmunohistoquímica con 3 +, hibridación fluorescente in situ [FISH] positiva, o hibridación cromogénica in situ [CISH] positiva).
- Tratamiento previo con fulvestrant.
- Tratamiento oncológico previo en el plazo de dos semanas antes del día 1 del ciclo 1.
- Radioterapia previa en el periodo de dos semanas antes del día 1 del ciclo 1.
- Tratamiento previo con > 1 tratamiento de quimioterapia citotóxica o > 2 tratamientos endocrinos para cáncer metastásico o avanzado.
- Toxicidad aguda y continua relacionada con el tratamiento que no se ha resuelto hasta el grado <= 1 o se ha considerado estable por parte del investigador.
- Hormonoterapia restitutiva simultánea.
- Metástasis conocidas del sistema nervioso central (SNC) activa o sin tratar (que progresan o requieren anticonvulsivos o corticoesteroides para el control sintomático);
- Antecedentes de otros tumores malignos en los 5 años anteriores.
- Incapacidad o negativa a tragar pastillas o recibir inyecciones i. m.
- Disfunción pulmonar o cardíaca clínicamente significativa
- Procedimiento quirúrgico importante o traumatismo significativo en un plazo de 28 días anteriores al día 1 del ciclo 1 o previsión de un procedimiento quirúrgico importante durante el ciclo del tratamiento en estudio.

E.5 End points

E.5.1

Primary end point(s)

PFS as determined by the investigator per RECIST v1.1

SSP determinada por parte del investigador según el sistema RECIST versión 1.1

E.5.1.1

Timepoint(s) of evaluation of this end point

26 months

26 meses

E.5.2

Secondary end point(s)

1. OS
2. ORR (partial response [PR] plus complete response [CR]) as determined by the investigator per RECIST v1.1
3. DOR as determined by the investigator per RECIST v1.1
4. CBR
5. Incidence of adverse events and serious adverse events
6. Clinically significant changes in vital signs, physical findings, and clinical laboratory results
7. Apparent clearance, volume of distribution, absorption rate constant of GDC-0810

1.SG
2. TRO (Remisión parcial (RP) más remisión completa (RC) determinda por parte del investigador según sistema RECIST 1.1.
3. DRO determinada por parte del investigador según el sistema RECIST versión 1.1.
4. TBC
5. Incidencia de aconteciminetos adversos y acontecimientos adversos graves.
6. Cambios clínicamente significativos de las constantes vitales, los datos obtenidos en la exploración física y los resultados clínicos del laboratorio.
7. Aclaramiento evidente, el volumen de distribución, la constante de la tasa de absorción de GDC-0810

E.5.2.1

Timepoint(s) of evaluation of this end point

1-6. 26 months
7. Predose and 3 hours postdose at Cycle 1 Day 1 and Cycle 3 Day 1

1-6. 26 meses.
7. Pre dosis y 3 horas post dosis en Ciclo 1 Día 1 y Ciclo 3 Día 1.

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

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Germany

Korea, Republic of

Spain

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of this study is defined as the date when the last patient, last visit (LPLV) occurs or the date at which the last data point required for statistical analysis (i.e., progression-free survival) or safety follow-up is received from the last patient, whichever occurs later, or when the Sponsor decides to stop the study.

La finalización del estudio se define como la fecha en la que se produce la última visita, de la última paciente o la fecha en la que se recibe el último punto de datos necesario para el análisis estadístico (es decir, SSP) o el seguimiento de la seguridad de la última paciente, lo que ocurra más tarde, o cuando el promotor decide detener 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

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:

144

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

152

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 Sponsor will offer post-trial access to the study drug (GDC-0810) free of charge to eligible patients in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product.

El promotor ofrecerá acceso al fármaco en estudio (GDC-0810) después del ensayo de manera gratuita a todas las pacientes idóneas de acuerdo con la política global de Roche sobre el acceso continuo al fármaco en etapa de investigación clínica.

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

2015-10-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-10-13

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

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