Clinical Trials Register

Summary
EudraCT Number:	2012-002552-16
Sponsor's Protocol Code Number:	RRK4368
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-10-15
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

UK - MHRA

A.2

EudraCT number

2012-002552-16

A.3

Full title of the trial

Cabazitaxel in platinum pre-treated patients with locally advanced or metastatic transitional cell carcinoma who developed disease progression within 12 months of platinum based chemotherapy.

A.3.1

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

A study of cabazitaxel to treat patients with confirmed locally advanced or metastatic Transitional Cell Carcinoma of the bladder or upper urinary tracts who have developed progressive disease within 12 months of their platinum based chemotherapy

A.3.2

Name or abbreviated title of the trial where available

Cab B1

A.4.1

Sponsor's protocol code number

RRK4368

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01668459

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	University Hospitals Birmingham NHS Foundation Trust
B.1.3.4	Country	United Kingdom
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-Aventis
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University Hospitals Birmingham NHS Foundation Trust
B.5.2	Functional name of contact point	Christopher Counsell
B.5.3	Address:
B.5.3.1	Street Address	Research & Development
B.5.3.2	Town/ city	1st Floor Education Centre
B.5.3.3	Post code	B15 2TH
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01213714185
B.5.5	Fax number	01213714204
B.5.6	E-mail	chris.counsell@uhb.nhs.uk

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	France
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 acetone solvate
D.3.9.1	CAS number	183133-96-2
D.3.9.2	Current sponsor code	RPR116258A
D.3.9.3	Other descriptive name	Jevtana
D.3.9.4	EV Substance Code	AS1
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Transitional cell carcinoma

E.1.1.1

Medical condition in easily understood language

Cancer of the bladder (transitional cell carcinoma)

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	LLT
E.1.2	Classification code	10061620
E.1.2	Term	Adenocarcinoma with transitional cell carcinoma of bladder
E.1.2	System Organ Class	100000004864

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 compare the overall response rate of patients administered cabazitaxel versus best supportive care (including single agent chemotherapy) in patients with transitional cell carcinoma who have previously progressed on a platinum-based regimen.

E.2.2

Secondary objectives of the trial

To compare progression free survival, overall survival, and quality of life assessment in patients administered cabazitaxel vs best supportive care (including chemotherapy). In addition, the safety and tolerability of both arms will be assessed in this patient population.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent
2. Age ≥ 18
3. Life expectancy ≥ 12 weeks
4. Patients with histology/cytology confirmed Transitional Cell Carcinoma (TCC) including mixed pathology with predominantly TCC, with Locally advanced (T4b) or metastatic (lymph node or visceral) TCC arising from bladder or upper urinary tracts
5. Treated patients with incidental prostate cancer (pT2, Gleason ≤ 6) and PSA (Prostate Specific Antigen) ≤ 0.5 ng/mL are eligible
6. Measurable disease as per RECIST Criteria 1.1
7. ECOG Performance Status 0-1
8. Previously received first line platinum based treatment
9. Recurrence within 12 months (by RECIST criteria version 1.1) from last cycle of chemotherapy

E.4

Principal exclusion criteria

1. Previous therapy with a taxane
2. Pure non TCC histologies
3. Grade II or more peripheral neuropathy
4. Prior surgery, radiation, chemotherapy, or other anti-cancer therapy within 4 weeks prior to enrolment in the study
5. Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus)
6. Inadequate organ and bone marrow function as evidenced by:
• Hemoglobin <9.0 g/dL
• Absolute neutrophil count <1.5 x 109/L,
• Platelet count <100 x 109/L,
• AST/SGOT and/or ALT/SGPT >2.5 x ULN;
• Total bilirubin >1.0 x ULN,
• 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 patients with creatinine clearance ≤ 30 mL/min should be excluded (see Appendix 6 for formula)
7. Symptomatic brain metastases or leptomeningeal disease (CT or MRI scan of the brain required only in case of clinical suspicion of central nervous system involvement)
8. History of another neoplasm except non-metastatic melanoma skin cancers, carcinoma in situ of the cervix, or cancer cured by surgery, small field radiation or chemotherapy < 5 years prior to randomization
9. History of inflammatory bowel disease, significant bowel obstruction
10. History of hypersensitivity to platinum, gemcitabine, taxanes, Polysorbate-80, or to compounds with similar chemical structures
11. Any of the following events within 6 months prior to randomization: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft surgery, clinically symptomatic and uncontrolled cardiovascular disease, or clinically significant arrhythmias (grade 3-4)
12. Concurrent treatment with strong inhibitors of cytochrome P450 3A4 or patients planning to receive these treatments (patients who were receiving treatment with such agents, a one-week washout period is required prior to randomization)
13. Women who are breastfeeding and women of child bearing potential (not postmenopausal (12 months of amenorrhea) or surgically sterile (absence of ovaries and/or uterus)) unless in agreement to use an adequate method of contraception during the treatment period and for 6 months after the last dose of the study drug. Men unless in agreement that they will use effective contraception (and condom to protect against exposure to seminal liquid) whilst participating in the trial and for 6 months after the last dose of study medication.

E.5 End points

E.5.1

Primary end point(s)

To compare Overall Response Rate (ORR) of patients administered cabazitaxel vs best supportive care (including single agent chemotherapy) in patients with transitional cell carcinoma (TCC) who have previously progressed on a platinum-based regimen.

CT abdomen & pelvis or MRI scan, chest x-ray (or CT chest/MRI in case of thoracic target lesion) and other exams as clinically indicated or other exams as clinically indicated to assess target and non-target lesions will be performed to assess disease status.

The overall response rate will be defined as the proportion of patients with confirmed RECIST-defined complete response (CR) or partial response (PR) relative to the total number of patients in the analysis population considered.

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline, following completion of 3 and 6 cycles of chemotherapy and whenever disease progression is suspected (e.g., symptomatic deterioration).

E.5.2

Secondary end point(s)

Progression free survival: Progression free survival (PFS) will be evaluated from the date of randomisation to the date of tumour progression or death (from any cause).
Overall survival (OS): defined as the time interval from the date of randomization to the date of death due to any cause. In absence of confirmation of death, survival time will be censored at the earlier of the last date the patient is known to be alive and the study cut-off date.
Quality of Life: will be assessed by using a validated instrument; the EuroQOL (EQ-5D).

Safety and tolerability

The number of patients in the safety population will be provided.In addition, reasons for treatment discontinuation as well as reasons for withdrawal from the Study will be summarized. Extent of exposure will be assessed as follows: Number of patients treated, number of cycles administered, duration of dosing (weeks), cumulative dose (mg/m²), dose intensity (mg/m²/3 weeks) and relative dose intensity (%) will be summarized.
Dose delays and dose reductions: Summary of safety data will also be performed by cycle (when applicable). For each of the safety parameters, a baseline value will be defined as the last value or measurement taken up to the first dose of cabazitaxel.
Adverse events will be considered as treatment-emergent if they first occur or worsen after the first day of dosing and up to 30 days after the last administration of cabazitaxel. The number and percentage of patients who die will be calculated and assessed based on the enrolled (treated) population.
Laboratory safety data: Haematological toxicities will be assessed from laboratory parameters. Worst NCI CTCAE grades of leukopenia, neutropenia, thrombocytopenia, and anaemia will be calculated according to the NCI common terminology criteria. Qualitative and quantitative results will be summarized for haematological toxicities. Qualitative data (worst NCI CTCAE grade) will be summarized by cycle and by patient. Biochemistry will be analyzed using the worst NCI CTCAE grade, whenever applicable (laboratory normal ranges, otherwise) calculated from laboratory values.

E.5.2.1

Timepoint(s) of evaluation of this end point

Progression free survival and overall survival: date of randomisation to the date of tumour progression or death (from any cause) (or survival at study cut-off date).
Quality of Life: Baseline, Week 6, Week 12, Week 18, Week 21
Safety and tolerability: all visits and for 30 days after final dose of study medication

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

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

The study will end on the date of the last subject of the last follow-up due to subject death, lost to follow-up or withdrawal of consent. All patients will be follow-ed up until death or until 12 months after the last patient has completed treatment.

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