Clinical Trials Register

Summary
EudraCT Number:	2017-000708-10
Sponsor's Protocol Code Number:	CPZP034A2410
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2017-07-21
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

2017-000708-10

A.3

Full title of the trial

A prospective international multicenter phase II study to evaluate the efficacy, safety and quality of life of oral daily pazopanib in patients with advanced and/or metastatic renal cell carcinoma after previous therapy with checkpoint inhibitor treatment

Estudio fase II, internacional, multicéntrico, prospectivo para evaluar la eficacia, la seguridad y la calidad de vida de pazopanib
administrado diariamente por vía oral, en pacientes con carcinoma de células renales avanzado y/o metastásico después de terapia previa con tratamiento con agentes inhibidores del control de la inmunidad (checkpoint inhibitors)

A.3.1

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

Study of efficacy and safety of pazopanib in patients with advanced and/or metastatic renal cell carcinoma after prior checkpoint inhibitor treatment

Estudio de la eficacia y la seguridad de pazopanib en pacientes con carcinoma de células renales avanzado y/o metastásico después de tratamiento previo con agentes inhibidores del control de la inmunidad (checkpoints inhibitors)

A.4.1

Sponsor's protocol code number

CPZP034A2410

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 Farmacéuctica 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	Javier Malpesa
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	+3493 3064464
B.5.5	Fax number	+3493 3064615
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	Yes
D.2.1.1.1	Trade name	Votrient
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm 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	Votrient
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	PAZOPANIB HYDROCHLORIDE
D.3.9.1	CAS number	635702-64-6
D.3.9.4	EV Substance Code	SUB31270
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	Votrient
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm 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	Votrient
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	PAZOPANIB HYDROCHLORIDE
D.3.9.1	CAS number	635702-64-6
D.3.9.4	EV Substance Code	SUB31270
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	400
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 and/or metastatic renal cell carcinoma

Carcinoma de células renales avanzado y/o metastásico.

E.1.1.1

Medical condition in easily understood language

Kidney cancer

Cancer renal

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	20.0
E.1.2	Level	HLT
E.1.2	Classification code	10068208
E.1.2	Term	Renal neoplasms malignant
E.1.2	System Organ Class	100000005104

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 assess the progression free survival based on local investigator assessment

Evaluar la supervivencia libre de progresión basado en la evaluación del investigador local

E.2.2

Secondary objectives of the trial

To assess overall response rate and clinical benefit rate based on local investigator assessment
To assess overall survival
To assess duration of response in patients with confirmed complete response (CR) or partial response (PR)
To evaluate safety and tolerability
To assess quality of life

Evaluar la tasa de respuesta global y la tasa de beneficio clínico basado en la evaluación del investigador local
Evaluar la supervivencia global
Evaluar la duración de la respuesta en pacientes con respuesta
completa (RC) o respuesta parcial (RP) confirmada
Evaluar la seguridad y la tolerabilidad
Evaluar la calidad de vida

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patient is >/= 18 years old at the time of informed consent.
Patient has histologically confirmed locally recurrent or metastatic predominantly clear cell renal cell carcinoma.
Patient must have measurable disease based on RECIST 1.1 criteria
Patient must have received prior systemic therapy with an immune checkpoint inhibitor (monotherapy or combination) as 1st or 2nd line RCC treatment. Note: patients with prior TKI treatment as monotherapy or in combination with immune checkpoint inhibitor are allowed; however, treatment with immune checkpoint inhibitor (monotherapy or in combination) must have been the last treatment prior to study entry.
Last dose of immune checkpoint inhibitor therapy must have been received 4 or more weeks before start of study treatment
Patient must have a Karnofsky performance status ≥70%.

Pacientes con >/= 18 años en el momento del consentimiento informado.
Pacientes con carcinoma de células renales predominantemente claras, localmente recurrente o metastásico, confirmado histológicamente.
Los pacientes deberán presentar enfermedad medible basado en los criterios RECIST 1.1.
Los pacientes deberán haber recibido terapia sistémica previa con un agente inhibidor del control de la inmunidad
(monoterapia o combinación), como tratamiento de 1ª o de 2ª línea para el CCR. Nota: se permiten los pacientes con
tratamiento con inhibidor de la tirosina quinasa (TKI) en monoterapia o en combinación con inhibidor del control de la
inmunidad; sin embargo, el tratamiento con el inhibidor del control de la inmunidad (monoterapia o en combinación) deberá haber sido el último tratamiento previo antes del inicio del estudio.
La última dosis de la terapia con inhibidor del control de la inmunidad deberá haberse recibido 4 o más semanas antes del inicio del tratamiento del estudio.
Los pacientes deberán presentar un estado funcional de Karnofsky ≥70%.

E.4

Principal exclusion criteria

Renal cell carcinoma without any clear (conventional) cell component
Presence of Central Nervous System (CNS) metastases
Prior treatment with bevacizumab that was not given in combination with immune checkpoint inhibitor therapy.
Prior treatment with more than 2 lines of therapy (combination treatments are considered 1 line of therapy)
Patient has not recovered from toxicity from prior immune checkpoint inhibitor therapy. Recovery is defined as ≤ CTCAE Grade 1, except for liver function test (LFT) levels which must be <Grade 1.
Patients receiving prohibited concomitant medications that cannot be discontinued or replaced by safe alternative medication at least 5 half-lives of the concomitant medication or 7 days, whichever is longer, prior to the start of pazopanib treatment.
Administration of any investigational drug within 4 weeks prior to the first dose of study treatment

Carcinoma de células renales sin ningún componente de células claras (convencional).
Presencia de metástasis del sistema nervioso central.
Tratamiento previo con bevacizumab que no haya sido administrado en combinación con terapia con agente inhibidor
del control de la inmunidad.
Tratamiento previo con más de 2 líneas de terapia (los tratamientos de combinación son considerados 1 línea de
terapia),
Pacientes que no se hayan recuperado de la toxicidad de la terapia previa con inhibidor del control de la inmunidad. La
recuperación se define como ≤ grado 1 de los criterios de terminología común de acontecimientos adversos del Instituto
Nacional de Cáncer (CTCAE-NCI), excepto para los niveles de las pruebas de función hepática (PFH) que deberá ser < grado 1.
Enfermedad recurrente menos de 6 meses desde la última dosis de la terapia neoadyuvante o adyuvante previa (incluyendo TKI del VEGF-R)
Pacientes que reciban medicaciones concomitantes prohibidas que no puedan ser suspendidas o sustituidas por medicación alternativa segura al menos 5 semividas de la medicación concomitante o 7 días, lo que sea más largo, antes del inicio del tratamiento con pazopanib.
Administración de cualquier fármaco en investigación dentro de las 4 semanas antes de la primera dosis del tratamiento del estudio

E.5 End points

E.5.1

Primary end point(s)

Progression free survival

Supervivencia libre de progresión (SLP)

E.5.1.1

Timepoint(s) of evaluation of this end point

After all patients have received a minimum of 6 cycles of study treatment or have discontinued study treatment early and at the end of study

Después de que todos los paciente hayan recibido un tratamiento mínimo de 6 ciclos o hayan discontinuado prematuramente y al final del studio.

E.5.2

Secondary end point(s)

-Overall Response Rate and Clinical Benefit Rate based on local
investigator assessment as per RECIST 1.1
-Overall survival
-Duration of Response in the subset of patients with confirmed CR / PR
-Safety and tolerability
-PRO assessed by EQ-5D and FKSI-DRS questionnaires

-Respuesta global y la tasa de beneficio clínico basado en la evaluación del investigador local segun Recist 1.1.
-Supervivencia global
-Duración de la respuesta en pacientes con respuesta completa (RC) o respuesta parcial (RP) confirmada
-Seguridad y la tolerabilidad
-Calidad de vida mediante cuestionarios EQ-5D y FKSI-DRS

E.5.2.1

Timepoint(s) of evaluation of this end point

ORR, OS, DOR will be evaluated at the same time as the primary endpoint and at the end of study; however, some patients may not have reached these endpoints at the time of the primary endpoint evaluation so the secondary endpoint results at the end of the study should be considered more meaningful.

La tasa de respuesta global, la supervivencia global y la duración de la respuesta serán evaluadas en el mismo que la variable principal y al final del estudio; sin embargo es posible que algunos pacientes no hayan alcanzado dichas variables en el momento de la evaluación de la variable primaria por lo que los resultados de la evaluación realizadas al final del estudio se considerarán más significativas.

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

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

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

Argentina

Austria

Canada

Chile

Czech Republic

France

Germany

Hungary

Japan

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

2 years after the last patient is enrolled or when all patients have died or discontinued from study and are no longer being followed for survival, whichever occurs first

2 años tras la inclusión del último paciente o cuando hayan fallecido o discontinuado todos los pacientes y no vaya a hacer un seguimiento de supervivencia de los mismos, lo que ocurra antes.

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

140

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 are still deriving benefit from the treatment at the end of the study, in the opinion of the investigator, should be switched to a local prescription in case Votrient® is commercially available and reimbursed in that country. For countries in which Votrient® is not reimbursed, nor commercially available or for patients who cannot afford treatment, Novartis will make every effort to continue to provide treatment with pazopanib through another program per local regulations

Los pacientes en los que al final del estudio el tratamiento siga mostrando beneficio a criterio del investigador, pasarán a ser tratados con Votrient comercial si éste está disponible y se rembolsa. En los paises en los que Votrient no se reembolsa o no está disponible de forma comercial o para los pacientes que no puedan permitirse el tratamiento, Novartis hará cualquier esfuerzo para seguir el tratamiento con pazopanib a través de otro tipo de programa según las regulaciones locales del pais

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

2017-09-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-09-25

P. End of Trial
P.	End of Trial Status	Ongoing

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