Clinical Trials Register

Summary
EudraCT Number:	2012-002826-55
Sponsor's Protocol Code Number:	SECAVIN-12
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-01-29
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

Netherlands - Competent Authority

A.2

EudraCT number

2012-002826-55

A.3

Full title of the trial

A randomised Phase II/III study of cabazitaxel versus vinflunine in metastatic or locally advanced transitional cell carcinoma of the urothelium

Een gerandomiseerde Fase II/III studie met cabazitaxel versus vinflunine in uitgezaaide of lokaal gevorderde transitioneel celcarcinoom van het urotheel

A.3.1

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

A randomised study of cabazitaxel versus vinflunine in bladder carcinoma.

Een gerandomiseerde studie van cabazitaxel versus vinflunine in blaas kanker

A.3.2

Name or abbreviated title of the trial where available

Cabazitaxel vs. vinflunine in metastatic or locally advanced TCCU

A.4.1

Sponsor's protocol code number

SECAVIN-12

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	Associació Per a la Recerca Oncològica (APRO)
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	European Union
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Per a la Recerca Oncològica (APRO)
B.5.2	Functional name of contact point	Inmaculada Musté
B.5.3	Address:
B.5.3.1	Street Address	Passeig Marítim 25-29
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08003
B.5.3.4	Country	Spain
B.5.4	Telephone number	003493248 30 00
B.5.5	Fax number	003493248 32 54
B.5.6	E-mail	oncologia.apro@gmail.com

D. IMP Identification
D.IMP: 1
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	JAVLOR
D.2.1.1.2	Name of the Marketing Authorisation holder	Pierre Fabre Médicament
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 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	VINFLUNINE
D.3.9.1	CAS number	162652-95-1
D.3.9.4	EV Substance Code	SUB00063MIG
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	25
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	JEVTANA
D.2.1.1.2	Name of the Marketing Authorisation holder	SANOFI
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	CABAZITAXEL
D.3.2	Product code	XRP6258
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.3.9.3	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	Yes
D.3.11.13.1	Other medicinal product type	Antinieoplasic agent. Taxane

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 or locally advanced transitional cell carcinoma of the urothelium

E.1.1.1

Medical condition in easily understood language

Bladder Cancer

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	17.1
E.1.2	Level	LLT
E.1.2	Classification code	10046714
E.1.2	Term	Urothelial carcinoma bladder
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	17.1
E.1.2	Level	PT
E.1.2	Classification code	10005084
E.1.2	Term	Bladder transitional cell carcinoma
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

Phase II part:
-efficacy of cabazitaxel compared to vinflunine in terms of improved objective response rate (ORR) of subjects with metastatic or locally advanced previously treated TCCU.
Phase III part:
-efficacy of cabazitaxel compared to vinflunine in terms of improved OS of subjects with metastatic or locally advanced, previously treated TCCU.

E.2.2

Secondary objectives of the trial

PHASE II part
- efficacy of cabazitaxel compared to vinflunine in terms of improved progression-free survival (PFS) and OS
- safety profile and tolerability of cabazitaxel

PHASE III part
- efficacy of cabazitaxel compared to vinflunine in terms of improved ORR and PFS
- safety profile and tolerability of cabazitaxel

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-written informed consent
-histologically confirmed TCCU (urinary bladder, urethra, ureter or renal pelvis). Patients with mixed histology may be enrolled if TCCU is the predominant component (i.e., > 50% of the histopathology sample) with the exception of neuroendocrine or small cell carcinoma.
-advanced disease defined as a locally advanced tumour considered unresectable (T4b), node involvement in the inguinal area or above the aortic bifurcation (that are considered to be distant nodes and so metastasis) or metastasis in distant organs.
-The patient should have received one prior platinum-based chemotherapy treatment for locally advanced or stage IV TCCU. Prior platinum-based adjuvant or neoadjuvant therapy is allowed if more than 6 months have elapsed since the end of adjuvant or neoadjuvant therapy till tumour relapse.
-at least one measurable tumour lesion (measurable disease, as defined by the RECIST criteria v1.1), for the phase II part of the study. If all sites of measurable disease have been irradiated, one site must have demonstrated growth after irradiation. For phase III part, patients with only non measurable disease are allowed for enrolment.
-Age ≥18 years.
-ECOG PS 0 or 1.
-no more than ONE of the following unfavourable risk factors:
a)haemoglobin <10 g/dL
b)presence of liver metastasis
c)ECOG PS 1
-Life expectancy of at least 12 weeks.
- Adequate hematologic, hepatic, and renal function, defined by:
a)Platelet count ?100 x109/L
b)Absolute neutrophil count (ANC) >1.5x109/L
c)Serum creatinine ≤1.5 times the upper limit of normality (ULN). If creatinine 1.0 1.5 xULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with creatinine clearance <50 mL/min should be excluded)
d)Alanine aminotransferase (ALT/SGPT), aspartate aminotransferase (AST/SGOT) and alkaline phosphatase (AP) ?2.5 ×ULN (<5 ×ULN in the presence of liver metastasis), and serum total bilirubin ?1.0 ×ULN.
-Females of childbearing potential must have a negative serum pregnancy test within 7 days of study entry. Patients of childbearing potential who participate in this study must use effective contraceptive methods (e.g., abstinence, intrauterine device, oral or injectable contraceptives, a double barrier method or surgical sterility) to prevent pregnancy starting as soon as the informed consent form is signed and continuing for at least 13 weeks after the last dose of the study medication is administered

E.4

Principal exclusion criteria

-Patients that have 2 or more of the following unfavourable risk factors:
a)Haemoglobin <10 g/L
b)Liver metastasis
c)ECOG PS 1.
2)Women who are currently pregnant or breast-feeding.
-Any unresolved non-hematologic AE grade >1 (NCI-CTCAE, Version 4.0) from previous anti-cancer therapy (other than alopecia)
-Patients who had undergone major surgery, radiation therapy or treatment with chemotherapy or any investigational agent within 28 days prior to Study day 1.
-Evidence of severe or uncontrolled systemic disease or any concurrent condition (including uncontrolled diabetes mellitus) which in the Investigator's opinion makes it undesirable for the subject to participate in the study or which would jeopardize compliance with the protocol.
-History of another neoplasm. Patients with prior history of either non-metastatic non melanoma skin cancers; carcinoma in situ of the cervix; or cancer cured by surgery, small field radiation or chemotherapy ?3 years prior to randomisation; or treated patients with early stage and low risk prostate cancer (?pT2 N0 M0, Gleason ?6 and Prostate-specific antigen [PSA] ?0.5 ng/mL) at study entry will be eligible.
-History of hypersensitivity reactions to taxanes (docetaxel) (cabazitaxel specific criteria), vinca alkaloids (vinflunine specific criteria) or to any of the formulation excipients, including polysorbate 80 (cabazitaxel specific criteria).
-Patients with clear evidence or symptoms of central nervous system metastasis (cabazitaxel specific criteria).
-Clinically significant cardiac condition demonstrated by myocardial infarction or thromboembolic events in the 6 months prior to the study treatment initiation, serious or unstable angina pectoris, New York Heart Association (NYHA) class III or IV congestive heart failure (see Appendix VI) (vinflunine specific criteria).
-Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are already on these treatments)

E.5 End points

E.5.1

Primary end point(s)

PHASE II part:
-ORR, which includes the sum of the complete and partial responses (CR+PR)

PHASE III part:
-OS

E.5.1.1

Timepoint(s) of evaluation of this end point

PHASE II part:
-ORR; at the end of phase II part (see protocol)

PHASE III part:
-OS; at the momment of the death.

E.5.2

Secondary end point(s)

PHASE II part:
-PFS
-OS
-Adverse events

PHASE III part:
-ORR
-PFS
-AEs

E.5.2.1

Timepoint(s) of evaluation of this end point

PHASE II part:
-PFS; when progression occurs
-OS; at the momment of the death
-Adverse events; at the end of phase II part (see protocol)

PHASE III part:
-ORR: at the end of the sudy (see protocol)
-PFS; when progression occurs
-AEs; at the end of the study

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)

Yes

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

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

LVLS

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:

186

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

186

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

372

F.4.2.2

In the whole clinical trial

372

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)

None

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

2013-01-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-07-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-01-12

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