Clinical Trials Register

Summary
EudraCT Number:	2011-000493-56
Sponsor's Protocol Code Number:	PIM4973g
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:	2011-09-07
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

2011-000493-56

A.3

Full title of the trial

A PHASE II, OPEN-LABEL, RANDOMIZED STUDY OF GDC-0980 VERSUS EVEROLIMUS IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA WHO HAVE PROGRESSED ON OR FOLLOWING VEGF-TARGETED THERAPY

ESTUDIO DE FASE II ABIERTO, RANDOMIZADO DE GDC-0980 FRENTE A EVEROLIMUS EN PACIENTES CON CARCINOMA DE CÉLULAS RENALES METASTÁSICO QUE HAN MANIFESTADO PROGRESIÓN DE LA ENFERMEDAD DURANTE O DESPUÉS DE UN TRATAMIENTO DIRIGIDO CONTRA VEGF

A.3.1

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

An evaluation of the investigational drug GDC-0980 in patients with metastatic kidney cancer who have already received up to three therapies, with the approved drug everolimus as a comparison

Evalaución del fármaco GDC-0980 en pacientes con cancer renal metastásico, que han recibido hasta 3 tratamientos, en comparación con el fármaco aprobado everolimus

A.4.1

Sponsor's protocol code number

PIM4973g

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	CH-4070
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	----
B.5.5	Fax number	----
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-0980
D.3.2	Product code	GDC-0980 (RO5490254)
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.3.9.1	CAS number	1032754-93-0
D.3.9.2	Current sponsor code	GDC-0980 (RO5490254)
D.3.9.3	Other descriptive name	PI3K/mTOR INHIBITOR
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	10
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	Afinitor 5 mg tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited, UK
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	Yes
D.2.5.1	Orphan drug designation number	EU/3/07/449
D.3 Description of the IMP
D.3.1	Product name	everolimus
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.3.9.1	CAS number	159351-69-6
D.3.9.3	Other descriptive name	EVEROLIMUS
D.3.9.4	EV Substance Code	SUB02065MIG
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	5
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	Yes
D.3.11.13.1	Other medicinal product type	Everolimus (mTOR inhibitor) is a derivative of sirolimus (= rapamycin). S. is a macrolide product of the bacterium Streptomyces hygroscopicus. Research ongoing on everolimus for use in cancers.
D.IMP: 3
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	Afinitor 10 mg tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited, UK
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	Yes
D.2.5.1	Orphan drug designation number	EU/3/07/449
D.3 Description of the IMP
D.3.1	Product name	everolimus
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.3.9.1	CAS number	159351-69-6
D.3.9.3	Other descriptive name	EVEROLIMUS
D.3.9.4	EV Substance Code	SUB02065MIG
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	10
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	Yes
D.3.11.13.1	Other medicinal product type	Everolimus (mTOR inhibitor) is a derivative of sirolimus (= rapamycin). S. is a macrolide product of the bacterium Streptomyces hygroscopicus. Research ongoing on everolimus for use in cancers.

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

METASTATIC RENAL CELL CARCINOMA

carcinoma de células renales metastásicos

E.1.1.1

Medical condition in easily understood language

METASTATIC RENAL CELL CARCINOMA

carcinoma de células renales metastásicos

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	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10038409
E.1.2	Term	Renal cell carcinoma NOS
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10038415
E.1.2	Term	Renal cell carcinoma stage unspecified
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10038407
E.1.2	Term	Renal cell cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

?To evaluate the efficacy of GDC-0980 versus everolimus as measured by progression-free survival (PFS) defined as the time from randomization to disease progression

? Evaluar la eficacia de GDC-0980 frente a everolimus, que se determinará basándose en la supervivencia libre de progresión (SLP) definida como el tiempo transcurrido desde la randomización hasta la progresión de la enfermedad.

E.2.2

Secondary objectives of the trial

?To assess the clinical activity of GDC-0980 versus everolimus as measured by response rate, duration of response, and overall survival (OS)
?To evaluate the safety and tolerability of GDC-0980 versus everolimus
?To assess pharmacokinetic (PK) parameters (Cmax, Cmin) of GDC 0980 and everolimus

?Evaluar la actividad clínica de GDC-0980 frente a everolimus, que se determinará basándose en el índice de respuesta, la duración de la respuesta y la supervivencia global (SG)
?Evaluar la seguridad y la tolerancia de GDC-0980 frente a everolimus
?Evaluar los parámetros farmacocinéticos (FC) (Cmax, Cmin) de GDC 0980 y everolimus

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

?Histologically or cytologically documented, incurable metastatic renal cell carcinoma with clear-cell component that progressed on or within 6 months of stopping VEGF-targeted therapy
?Age ? 18 years
?Karnofsky Performance Status Score (KPSS) of ? 70%
?Disease that is measurable per RECIST v1.1
?Adequate hematologic and end organ function

? histológica y citológicamente documentado carcinoma de células renales metastásico con claro componente celular que ha progresado en o dentro de 6 meses tras interrupción de tratamiento VEGF
-Edad >=18 años
?Índice del estado funcional de Karnofsky >=70%
?Enfermedad medible de acuerdo con los criterios RECIST v1.1
?Función hematológica y de órganos diana adecuada

E.4

Principal exclusion criteria

?Requirement for chronic antihyperglycemic therapy
?Current dyspnea at rest or any requirement for supplemental oxygen therapy to perform activities of daily living
?Decreased oxygen saturation with exercise (pulse oximeter <88%)
?Previously established diagnosis of pulmonary fibrosis of any cause
?Current unstable angina
?History of myocardial infarction within 6 months prior to Day 1
?New York Heart Association (NYHA) Class II or greater congestive heart failure
?Clinically significant liver disease
?Known HIV infection
?Active infection requiring IV antibiotics
?Active autoimmune disease that is not controlled by nonsteroidal anti inflammatory drugs
?Pregnancy, lactation, or breastfeeding
?Leptomeningeal disease as a manifestation of cancer
?Untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control).

?Pacientes que requieran tratamiento antihiperglucémico
?Pacientes que en la actualidad presenten disnea en reposo o requieran oxigenoterapia complementaria para realizar las actividades diarias
?Reducción de la saturación de oxígeno durante el ejercicio (< 88% en oximetría de pulso)
?Diagnóstico previamente establecido de fibrosis pulmonar de cualquier etiología
?Angina de pecho inestable en la actualidad
?Antecedentes de infarto de miocardio en los 6 meses previos al día 1
?Insuficiencia cardíaca congestiva clase II o superior de la New York Heart Association (NYHA)
?Antecedentes clínicamente significativos de enfermedad hepática
?Infección por VIH confirmada
?Infección activa que requiera antibióticos IV
?Enfermedad autoinmune activa no controlada con fármacos antiinflamatorios no esteroideos
?Pacientes embarazadas o en período de lactancia
?Enfermedad leptomeníngea como manifestación del cáncer
?Metástasis del sistema nervioso central (SNC) no tratadas o activas (en progresión

E.5 End points

E.5.1

Primary end point(s)

Progression-free survival (PFS)

supervivencia libre de progresión (SLP)

E.5.1.1

Timepoint(s) of evaluation of this end point

After approximately 60 PFS events have occurred (estimated to occur approximately 23 months after study start).

Tras aproximadamente 60 acontecimientos de SLP (estimando qeu ocurra aprox 23 meses después de inicio de estudio)

E.5.2

Secondary end point(s)

Response rate, duration of response, overall survival, safety, tolerability, PK parameters

Respuesta tumoral, Duración de la respuesta objetiva, SG, seguridad, tolerabilidad, parámetros de farmacocinética

E.5.2.1

Timepoint(s) of evaluation of this end point

Final analyses after approximately 60 PFS events have occurred. Interim analyses for safety and PK parameters after the first 10 patients in each arm have undergone the first tumor assessment while receiving study treatment (GDC-0980 or everolimus); and again when the same is the case for 20 and 30 patients in each arm.

Análisis final tras aproximadamente 60 acontecimientos de SLP.
Análisis intermedio para seguridad y PK en los 10 primeros pacientes de cada brazo con la primera valoración del tumor con tratamientod e estudio.

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

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

Yes

E.8.2.3.1

Comparator description

everolimus

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

France

Germany

Spain

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

After the patients are discontinued from the study treatment, they will
still be followed up for survival. Survival follow-up information will be
collected via telephone calls approximately every 3 months until death,
loss to study follow-up, patients withdraw consent, or study
termination by Genentech

Despues de que los pacientes hayan discontinuado el tratamiento del estudio, serán seguidos para supervivencia. La información del seguimiento de supervivencia se recogerá mediante llamadas telefónicas aproximadamente cada 3 meses hasta fallecimiento, pérdida de seguimiento, retirada del consentimiento o terminación del estudio por Genentech.

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:

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

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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 who discontinue study drug for any reason (i.e. an AE, etc.) other than disease progression will continue to be followed up until the patient has documented disease progression, withdrawal of consent, lost to follow up or starts another anti-cancer therapy.
Upon completion of the trial, patients should be treated at the discretion of the treating physician.

Pacientes que han discontinuado el fármaco de estudio pro alguan razón distinta a la progresión de la enfermedad continuarán siendo seguidos hasta la documentaciópn de progresiónd e enfermedad, perdida de seguimiento o inicio de otro tratamiento contra el cancer.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	National Cancer Research Network (NCRN) at
G.4.3.4	Network Country	United Kingdom

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2011-09-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-09-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-06-23

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