Clinical Trials Register

Summary
EudraCT Number:	2011-004627-12
Sponsor's Protocol Code Number:	CABASEM-SOGUG
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:	2011-10-28
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

2011-004627-12

A.3

Full title of the trial

Phase II Study of Weekly Cabazitaxel for Advanced Prostate Cancer in "Unfit" Hormone-Refractory Patients Previously Treated with Docetaxel.

Ensayo Fase II de Cabazitaxel Semanal en Cancer de Prostata Avanzado en Pacientes "Unfit" Hormono-Resistentes Previamente Tratados con Docetaxel.

A.3.1

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

Study of Weekly Cabazitaxel for Advanced Prostate Cancer.

Estudio de Cabazitaxel Semanal en Cancer de Prostata Avanzado.

A.4.1

Sponsor's protocol code number

CABASEM-SOGUG

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	SOGUG - Spanish Oncology Genitourinary Group
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Sanofi
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	APICES SOLUCIONES, S.L.
B.5.2	Functional name of contact point	Juan Luis Sanz
B.5.3	Address:
B.5.3.1	Street Address	Salamanca, 7
B.5.3.2	Town/ city	Torrejón de la Calzada (MADRID)
B.5.3.3	Post code	28991
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34918166804103
B.5.5	Fax number	+34918169172
B.5.6	E-mail	juanluis.sanz@apices.es

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	Spain
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 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.3.9.1	CAS number	183133-96-2
D.3.9.3	Other descriptive name	CABAZITAXEL
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.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 Prostate Cancer

Cancer de Prostata Avanzado

E.1.1.1

Medical condition in easily understood language

Prostate Cancer

Cáncer de próstata

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	10062904
E.1.2	Term	Hormone-refractory prostate cancer
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	PT
E.1.2	Classification code	10036920
E.1.2	Term	Prostate cancer stage IV
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

Evaluate the activity of the weekly administration of cabazitaxel as time to PSA progression according to the PCCTWG II criteria.

Evaluar la actividad de la administración de cabazitaxel semanal como el tiempo hasta la progresión por PSA determinado según los criterios de PCCTWG II.

E.2.2

Secondary objectives of the trial

Evaluate the rate of biochemical response by means of PSA determination and defined as the percentage of patients with a reduction of 30%, 50% and 80% with respect to baseline.

Evaluate the overall response rate of the disease according to modified RECIST criteria.

Evaluate overall survival.

Evaluate the safety and tolerability profile of cabazitaxel.

Determine the pain response in patients with stable pain at baseline by means of the MPQ-sf (McGill Pain Questionnaire - short form).

Evaluate the correlation between Charlson co-morbidity index and the ADL/IADL dependence indexes in predicting survival and toxicity in patients with hormone-refractory prostate cancer previously treated with docetaxel.

Evaluar la tasa de respuesta bioquímica mediante la determinación del PSA definido como el porcentaje de pacientes con una reducción del 30%, 50% y 80% respecto a basal.

Evaluar la tasa de respuesta objetiva de la enfermedad según los criterios RECIST modificados.

Determinar la supervivencia global.

Evaluar el perfil de seguridad y tolerabilidad de cabazitaxel.

Determinar la respuesta al dolor en pacientes con dolor estable en basal mediante el cuestionario MPQ-sf (McGill Pain Questionnaire - short form).

Evaluación de la correlación entre el índice de comorbilidad de Charlson y los índices de dependencia ADL/IADL en la predicción de la supervivencia y la toxicidad en pacientes con cáncer de próstata hormono-resistentes que hayan recibido previamente docetaxel.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients who have given written informed consent.
2. Age ? 18 years.
3. ECOG 0-2.
4. Patients with a histologic or cytologic diagnosis of advanced prostate cancer (any Gleason grade).
5. Previous and ongoing castration by orchiectomy or LHRH agonists. Antiandrogen must be discontinued prior to study start.

6. Disease progression, clinically or radiologically documented, during or after treatment with docetaxel, with a minimum cumulative dose of 225 mg/m2.
7. ?Unfit? patients defined as patients who satisfy at least one of the following criteria:
- Age ? 75 years
- Dose reduction due to febrile neutropenia during the previous treatment with docetaxel
- Radiation therapy affecting more than 25% of bone marrow reserve
- ECOG 2
8. Documented metastatic disease and progressing after docetaxel treatment. Progression criteria is considered any of the following three or more than one at once:
- Progressive elevation of PSA measured in three successive determinations one week difference between them at least;
- Should be considered progression of measurable disease by RECIST criteria;
- Bone progression as evidenced by the appearance of two or more new lesions on bone scan.
9. Patients who have received a maximum of two prior chemotherapy for metastatic disease.
10. Prior anticancer therapy should have been interrupted 28 days before the start of study treatment (the patient may have continued treatment with prednisone 5 mg bid).
11. Adequate blood, liver and kidney function:
- Hemoglobin > 9.0 g/dl
- ANC > 1.5 x 10E9/L
- Platelets > 100 x 10E9/L
- AST/SGOT and ALT/SGPT < 2.5 x ULN
- Bilirubin < 1.0 x ULN
- Creatinine <1.5 mg/dL x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with creatinine clearance <60 mL/min should be excluded (see Annex 7 for formula)
12. Adequate baseline cardiac function (LVEF ? 50%).
13. Life expectancy ? 12 weeks.
14. Patients must agree to use an effective contraceptive method during treatment with the study drug and up to 1 month after ending the treatment.

1. Pacientes que hayan otorgado el consentimiento informado por escrito.
2. Edad ? 18 años.
3. ECOG 0-2.
4. Pacientes con diagnóstico histológico o citológico de cáncer de próstata avanzado (cualquier Gleason).
5. Castración mediante orquiectomía o mediante agonistas LHRH previa o actual. Se deberá retirar el antiandrógeno antes del inicio del estudio.
6. Progresión de la enfermedad documentada clínica o radiológicamente durante o tras tratamiento con docetaxel, con una dosis mínima acumulada de 225 mg/m2.
7. Pacientes ?unfit? definido como pacientes que cumplan al menos uno de los siguientes criterios:
- Edad ? 75 años
- Reducción de dosis debido a neutropenia febril durante el tratamiento previo con docetaxel
- Radioterapia afectando a más del 25% de la reserva medular
- ECOG 2
8. Enfermedad metastásica documentada y en progresión tras tratamiento con docetaxel. Se considerará criterios de progresión cualquiera de los tres siguientes o varios de ellos a la vez:
- Elevación progresiva de PSA medida en tres determinaciones sucesivas con una semana de diferencia entre ellas como mínimo;
- En caso de enfermedad medible se considerará progresión según los criterios RECIST;
- Progresión ósea evidenciada por la aparición de dos o más lesiones nuevas en el rastreo óseo.
9. Pacientes que hayan recibido un máximo de dos líneas de quimioterapia previa para la enfermedad metastásica.
10. El tratamiento previo antineoplásico debe haberse suspendido 28 días antes del inicio del tratamiento del estudio (el paciente puede haber proseguido tratamiento con prednisona 5 mg bid).
11. Adecuada función hematológica, hepática y renal:
- Hemoglobina > 9.0 gr/dl
- RAN > 1.5 x 10E9/L
- Plaquetas > 100 x 10E9/L
- AST/SGOT y ALT/SGPT < 2.5 x LSN
- Bilirrubina < 1.0 x LSN
- Creatinina <1.5 x LSN. Si la creatinina 1.0-1.5 x LSN, el aclaramiento de creatinina se deberá calcular de acuerdo a la fórmula CKD-EPI y los pacientes con aclaramiento de creatinina <60 mL/min deberán ser excluidos (véase Anexo 7 para la fórmula).
12. Adecuada función cardíaca basal (FEVI ? 50%).
13. Expectativa de vida ? 12 semanas.
14. Los pacientes deberán aceptar el uso de un método anticonceptivo adecuado durante el tratamiento con el fármaco del estudio y hasta 1 mes después de haber finalizado el tratamiento.

E.4

Principal exclusion criteria

1. Patients who received radiation therapy that exceeded 40% of the bone marrow reserve or that ended within the last 3 weeks prior to inclusion.
2. If being treated with radiation therapy, should be completed before the three weeks prior to initiation of treatment research.
3. Previous treatment with two or more chemotherapy regimens for metastatic disease. A new line of treatment is also when a patient receives again docetaxel after clinical, radiological or PSA progression to a prior regimen with docetaxel.
4. Previous treatment with chemotherapy or surgery in the last 4 weeks.
5. Peripheral neuropathy or stomatitis ? 2 (National Cancer Institute Common Terminology Criteria - NCI CTCAE vs. 4.03).
6. Any other type of cancer in the last 5 years, except for basal cell skin carcinoma.
7. Cerebral or leptomeningeal metastasis.
8. Myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass, congestive heart failure (NYHA class III or IV), stroke or transitory ischemic episodes.
9. Patients who present any severe or uncontrolled medical condition (including uncontrolled diabetes mellitus) or any other condition that may affect the patient?s participation and study compliance.
10. Previous treatment with cabazitaxel.
11. Known hypersensitivity (? grade 3)to cabazitaxel, polysorbate 80, prednisone or prednisolone, or docetaxel or paclitaxel.
12. Known history of active infection that requires systemic antibiotic or antifungal treatment.
13. Patients who are receiving or expect to receive treatment with strong inhibitors or strong inducers of cytochrome CYP450 3A4/5 (a one week wash-out period is necessary for patients who are already on these treatments) (see Annexes 5 and 6).
14. Patients being treated with any investigational product.

1. Pacientes que hayan recibido radioterapia que haya excedido el 40% de la reserva medular.
2. En caso de haber recibido tratamiento con radioterapia, debe haber finalizado antes de las tres semanas previas al inicio del tratamiento de investigación.
3. Dos o más líneas de quimioterapia previa para la enfermedad metastásica. Se considerará una nueva línea de tratamiento cuando el paciente reciba de nuevo docetaxel tras una progresión clínica, radiológica o por PSA, a un tratamiento previo con docetaxel.
4. Tratamiento previo con quimioterapia o cirugía en las últimas 4 semanas.
5. Neuropatía periférica o estomatitis ? 2 (National Cancer Institute Common Terminology Criteria - NCI CTCAE vs. 4.03).
6. Cualquier otro tipo de cáncer dentro de los últimos 5 años, salvo que se trate de carcinoma basocelular cutáneo.
7. Metástasis cerebrales o leptomeningeas.
8. Infarto de miocardio, agina pectoris grave/inestable, bypass de arteria coronaria/periférica, insuficiencia cardíaca congestiva (NYHA clase III o IV), ictus o ataque isquémico transitorio.
9. Pacientes que presenten cualquier condición médica severa o no controlada (incluido diabetes mellitus no controlada), o cualquier otra condición que pueda afectar a su participación y cumplimiento del estudio.
10. Tratamiento previo con cabazitaxel.
11. Hipersensibilidad (? grado 3) conocida al cabazitaxel, al polisorbato 80, a la prednisona o prednisolona, o al docetaxel o paclitaxel.
12. Historia conocida de infección activa que requiera tratamiento sistémico antibiótico o antifúngico.
13. Pacientes que estén recibiendo o tengan previsto un tratamiento con fármacos u otros productos inhibidores o inductores de la CYP450 3A4/5 (es necesaria una semana de lavado para pacientes que estén actualmente con ese tratamiento) (véase Anexo 5 y 6).
14. Pacientes en tratamiento con cualquier producto en investigación.

E.5 End points

E.5.1

Primary end point(s)

Time to PSA progression, according to the PCCTWG II criteria.

Tiempo hasta la progresión por PSA, según los criterios de PCCTWG II.

E.5.1.1

Timepoint(s) of evaluation of this end point

Until PSA progression

Hasta progresión de la enfermedad

E.5.2

Secondary end point(s)

1-Evaluate the rate of biochemical response by PSA determination defined as the percentage of patients with 30%, 50% and 80% reduction respect to baseline.

2-The proportion of patients with an objective tumoral response according to modified RECIST criteria. The response in measurable soft tissue lesions is determined by RECIST criteria. Progression of bone metastasis diagnosed by bone scan is defined by the appearance of two or more new confirmed lesions one month later.

3-Overall survival is calculated since the date of patient study enrolment till death.

4-Evaluate the safety and tolerability profile of cabazitaxel.

5-Determine the pain response in patients with stable pain at baseline by means of the McGill-Melzack MPQ-sf questionnaire, defined as >= 2 points with respect to baseline on the PPI scale without increase in the analgesic scale, or with a decrease of >= 50% in the use of analgesics without an increase in pain that is maintained for more than 3 weeks.

6-Evaluation of the correlation of the Charlson co-morbidity index and ADL/IADL dependency indexes with survival and toxicity in patients with hormone-refractory prostate cancer previously treated with docetaxel.

1-Evaluar la tasa de respuesta bioquímica mediante la determinación del PSA definido como el porcentaje de pacientes con una reducción del 30%, 50% y 80% respecto a basal.

2-Proporción de pacientes con respuesta tumoral objetiva según los criterios RECIST modificados. La respuesta en lesiones medibles de tejido blando, se determina mediante los criterios RECIST. La progresión de las metástasis óseas diagnosticadas por gammagrafía, se determina mediante la aparición de dos o más nuevas lesiones confirmadas un mes después.

3-La supervivencia global se calcula desde la fecha de entrada el estudio hasta el fallecimiento del Paciente.

4-Evaluar el perfil de seguridad y tolerabilidad de cabazitaxel.

5-Determinar la respuesta a dolor en pacientes con dolor estable en basal mediante el cuestionario McGill-Melzack MPQ-sf, definida como una reducción de >= 2 puntos respecto a basal en la escala PPI sin aumento en la escala de analgésicos o disminución >= 50% en el uso de analgésicos sin incremento del dolor que se mantiende durante más de 3 semanas.

6-Evaluación de la correlación del índice de comorbilidad de Charlson y los índices de dependencia ADL/IADL con la supervivencia y la toxicidad en pacientes con cáncer de próstata hormono-resistentes que hayan recibido previamente docetaxel.

E.5.2.1

Timepoint(s) of evaluation of this end point

1-Until PSA progression
2-Until end of treatment
3-Until death
4-Until end of treatment
5-Until end of treatment
6-Until death

1-Hasta progresion de la enfermedad
2-Hasta fin de tratamiento
3-Hasta fallecimiento
4-Hasta fin de tratamiento
5-Hasta fin de tratamiento
6-Hasta fallecimiento

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

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

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.8.3

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

last visit of the last subject undergoing the trial

última visita del último paciente en el ensayo

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

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

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.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)

Expected normal treatment of that condition.

Tratamiento según protocolo asistencial en cada centro participante.

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

2011-12-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-12-16

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

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