Clinical Trials Register

Summary
EudraCT Number:	2011-003415-31
Sponsor's Protocol Code Number:	ARD12166
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:	2012-06-26
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

2011-003415-31

A.3

Full title of the trial

Randomized Phase II Study of Cabazitaxel versus Topotecan in Small Cell Lung Cancer Patients with Progressive Disease during or after a First Line Platinum Based Chemotherapy

Estudio fase II, aleatorizado, de Cabazitaxel versus Topotecan en pacientes con Cáncer de Pulmón de Células Pequeñas con Enfermedad Progresiva durante o después de una primera línea de quimioterapia basada en platino

A.3.1

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

Cabazitaxel compared to topotecan for the treatment of small cell lung cancer

Cabazitaxel versus Topotecan para el tratamiento de Cáncer de Pulmón de Células Pequeñas

A.4.1

Sponsor's protocol code number

ARD12166

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1123-3503

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	Sanofi-aventis Recherche & Développement
B.1.3.4	Country	France
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	Sanofi-aventis Recherche & Développement
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	sanofi-aventis, s.a.
B.5.2	Functional name of contact point	CSU Director
B.5.3	Address:
B.5.3.1	Street Address	c/ Josep Pla nº2, 5ª planta
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08019
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34934859466
B.5.5	Fax number	+34934895466
B.5.6	E-mail	bibiana.figueres@sanofi.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	Jevtana
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi-aventis
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	Concentrate and solvent for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CABAZITAXEL
D.3.9.1	CAS number	183133-96-2
D.3.9.2	Current sponsor code	XRP6258
D.3.9.4	EV Substance Code	SUB31282
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	40
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.2.5	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	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	topotecan
D.3.9.1	CAS number	119413-54-6
D.3.9.3	Other descriptive name	TOPOTECAN HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB04921MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.5
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	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

Small Cell Lung Cancer

Cáncer de Pulmón de Células Pequeñas

E.1.1.1

Medical condition in easily understood language

Small Cell Lung Cancer

Cáncer de Pulmón de Células Pequeñas

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10041071
E.1.2	Term	Small cell lung cancer stage unspecified
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

E.2 Objective of the trial

E.2.1

Main objective of the trial

To demonstrate progression free survival (PFS) improvement for cabazitaxel compared to topotecan in patients with sensitive or resistant/refractory small cell lung cancer following a first line platinum based chemotherapy.

Demostrar la mejoría de la supervivencia libre de progresión (SLP) para cabazitaxel comparado con topotecán en pacientes con cáncer pulmonar de células pequeñas sensible o resistente/refractario después de una quimioterapia de primera línea basada en platino.

E.2.2

Secondary objectives of the trial

o To assess disease progression free rate at 12 weeks
o To assess Response Rate (RECIST 1.1) and duration of response
o To assess Overall Survival (OS)
o To assess the Safety (NCI-CTC version 4.03)
o To assess the Health-Related Quality of Life (HRQoL)

• Evaluar la tasa libre de progresión de la enfermedad a las 12 semanas
• Evaluar la Tasa de Respuesta (RECIST 1.1) y la duración de la respuesta
• Evaluar la Supervivencia Global (SG)
• Evaluar la Seguridad (NCI-CTC versión 4.03)
• Evaluar la Calidad de Vida Relacionada con la Salud (HRQoL)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

I 01. Histological/cytological proven locally advanced or metastatic small cell lung cancer with progressive disease during or after first line platinum based chemotherapy
I 02. Male or female ?18 years (or country's legal age of majority if >18 years)
I 03. Patients with measurable disease, RECIST (version 1.1)
I 04. ECOG performance status ?1

I 01. Cáncer pulmonar de células pequeñas metastático o localmente avanzado comprobado histológica/citológicamente con enfermedad progresiva durante o después de una primera línea de quimioterapia basada en platino.
I 02. Hombre o mujer > 18 años (o la edad legal de mayoría de edad del país si > 18 años)
I 03. Pacientes con enfermedad medible, RECIST (versión 1.1.)
I 04. Estado funcional de ECOG <1

E.4

Principal exclusion criteria

E 01. Absence of signed and dated Institutional Review Board (IRB)-approved patient informed consent form prior to enrollment into the study.
E 02. More than one prior chemotherapy regimen. Prior treatment with topotecan or taxanes.
E 03. Less than 28 days elapsed from prior treatment with chemotherapy, radiotherapy or surgery to the time of randomization. (Radiotherapy for bone pain palliation is allowed).
E 04. Adverse events (excluding alopecia) from any prior anticancer therapy of grade >1(National Cancer Institute Common Terminology Criteria [NCI CTCAE] v4.03) at the time of randomization.
E 05. Uncontrolled CNS metastases: patients with CNS metastases may have previous irradiation, only patients with SD or response to irradiation who are without CNS symptoms and on a maximum steroid dose of dexamethasone 8 mg daily or equivalent can be included.
E 06. Patients with known leptomeningeal metastases
E 07. History of other, invasive neoplasm requiring ongoing therapy.
E 08. Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to randomization
E 09. Any of the following within 6 months prior to study enrollment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, NYHA class III or IV congestive heart failure, stroke or transient ischemic attack.
E 10. Any severe acute or chronic medical condition, which could impair the ability of the patient to participate in the study or interfere with interpretation of study results
E 11. Known HIV disease, or active hepatitis B or C (systematic testing is not required).
E 12. Pregnant or breast-feeding woman. Positive serum or urine pregnancy test prior to randomization
E 13. Patient with reproductive potential (M/F) who do not agree to use an accepted and effective method of contraception during the study treatment period and for at least 6 months after the completion of the study treatment. The definition of "effective method of contraception" will be based on the investigator's judgment. Effective method of contraception should also be adapted to local regulation.
E 14. History of hypersensitivity to polysorbate 80
E 15. Inadequate organ and bone marrow function as evidenced by:
o Hemoglobin <9.0 g/dL
o Absolute neutrophil count <1.5 x 10 exp9/L
o Platelet count <100 x 10exp9/L
o AST/SGOT and/or ALT/SGPT >2.5 x ULN
o AP >2.5 x ULN. In case of liver metastases AP > 5 x ULN
o Total bilirubin >1.0 x ULN
o Serum Creatinine >1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated according to CKD-EPI formula, and creatinine clearance <60 mL/min will exclude the patient.

Relacionados con la metodología:

E 01. Ausencia del formulario de consentimiento informado del paciente firmado y fechado aprobado por el IRB/Comité ético antes de la inclusión en el estudio.

E 02. Más de un régimen de quimioterapia previo. Tratamiento previo con topotecan o taxanos.

E 03. Menos de 28 días transcurridos desde el
tratamiento previo con quimioterapia, radioterapia o cirugía al momento de la randomización. (Está permitida la radioterapia para paliar el dolor óseo).

E 04. Acontecimientos adversos (excluyendo alopecia) de cualquier terapia anticancerígena previa de grado > 1 (Criterios de Terminología Comunes del Instituto Nacional del Cáncer [NCI CTCAE] v4.03) en el momento de la randomización.

E 05. Metástasis incontroladas del SNC: pacientes con metástasis del SNC pueden tener irradiación previa, sólo los
pacientes con EE o respuesta a la irradiación que están sin síntomas en el SNC y con una dosis máxima de esteroides de dexametasona de 8 mg diarios o equivalente pueden ser incluidos.

E 06. Pacientes con metástasis leptomeníngea conocida
E 07. Antecedentes de otra neoplasia invasiva que requiera terapia en curso.

E 08. Participación en otro estudio clínico y cualquier tratamiento concomitante con cualquier fármaco en investigación dentro de los 30 días previos a la randomización.

E 09. Cualquiera de los siguientes dentro de 6 meses previos a la inclusión en el estudio: infarto de miocardio, angina de pecho grave/inestable, bypass de la arteria coronaria/periférica con injerto, insuficiencia cardíaca congestiva clase III o IV según la NYHA, accidente vascular cerebral o accidente isquémico transitorio.

E 10. Cualquier condición médica crónica o aguda grave, que pudiera perjudicar la capacidad del paciente de participar en el estudio o interferir en la interpretación de los resultados del estudio

E 11. Enfermedad HIV o hepatitis B o C activa conocida (no se requiere pruebas sistemáticas).

E 12. Mujeres embarazadas o en periodo de lactancia.
Test de embarazo positivo en suero o en orina previo a la randomización

E 13. Pacientes en edad fértil (M/F) que no acepten usar un método anticonceptivo aceptado y efectivo durante el periodo de tratamiento del estudio y por al menos 6 meses después de finalizado el tratamiento del estudio. La definición de método efectivo de anticoncepción” se basará en el criterio del investigador. El método efectivo de anticoncepción deberá ser adaptado además a la regulación local.

Relacionados con la quimioterapia:

E 14. Antecedentes de hipersensibilidad al polisorbato 80

E 15. Función inadecuada de la médula ósea y órganos según lo evidenciado por:
• Hemoglobina < 9,0 g/dL
• Recuento absoluto de neutrófilos < 1,5 x 109/L
• Recuento de plaquetas < 100 x 109/L
• AST/SGOT y/o ALT/SGPT > 2,5 x LSN
• FA >2,5 x LSN. En caso de metástasis del hígado FA > 5 x LSN
• Bilirrubina total > 1,0 x LSN
• Creatinina Sérica > 1,5 x LSN. Si la creatinina es 1,0 – 1,5 x LSN, se calculará el aclaramiento de creatinina de acuerdo con la fórmula CKD-EPI y un aclaramiento de creatinina <60 mL/min. excluirá al paciente (ver Apéndice A para la fórmula de cálculo)

E.5 End points

E.5.1

Primary end point(s)

progression free survival

Supervivencia libre de progresión

E.5.1.1

Timepoint(s) of evaluation of this end point

up to 24 months

Hasta 24 meses

E.5.2

Secondary end point(s)

Overall survival

Supervivencia global

E.5.2.1

Timepoint(s) of evaluation of this end point

up to 24 months

Hasta 24 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

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

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

Brazil

Canada

Chile

France

Germany

Greece

Hungary

Italy

Korea, Republic of

Norway

Poland

Romania

Russian Federation

Spain

Ukraine

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

Not applicable

No aplica

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:

103

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

104

F.4.2.2

In the whole clinical trial

172

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)

Not applicable

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-08-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-08-07

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-04-02

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Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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