Bristol Bladder Trial

Study Overview
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Brief Summary
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26 patients with invasive primary transitional cell carcinoma of the bladder will receive 4 cycles of combination chemotherapy consisting of Cabazitaxel and Cisplatin both given intravenously on day 1 of each 3 weekly cycle prior to radical cystectomy, to evaluate the overall response rate and to determine whether this approach warrants further research of a phase II/III study.Participation in 2 sub studies will also be offered to the participants. Contrast Magnetic resonance imaging (MRI ) scans will be taken at baseline and after cycle 1 and cycle 3. A pilot sub study involving the circulating tumour cell concentration from blood samples taken at baseline, prior to each cycle of chemotherapy and prior to surgery

Official Title
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A Phase II Trial of Combination Cabazitaxel and Cisplatin Chemotherapy in the Neo-adjuvant Treatment of Transitional Cell Carcinoma of the Urinary Bladder

Conditions
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Infiltrating Bladder Urothelial Carcinoma

Intervention / Treatment
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* Drug: Cabazitaxel + Cisplatin chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Histologically confirmed primary transitional cell carcinoma (TCC) of the urinary bladder T2 to T4 disease, N0 M0 determined by computerised tomography (CT) imaging and biopsy or transurethral resection Eastern Co-operative Oncology Group (ECOG) Performance status 0 or 1 Glomerular filtration rate (GFR) ≥60ml/min. Written, informed consent Exclusion Criteria ECOG Performance Status ≥ 2 Lymph node involvement or metastatic disease Prior surgery (except transurethral resection of bladder tumour), radiation, che-motherapy, or other anti-cancer therapy within 4 weeks prior to enrolment Active Grade ≥2 peripheral neuropathy Active secondary cancers History of severe hypersensitivity reaction (≥Grade 3) to polysorbate 80 containing drugs Other concurrent serious illness or medical conditions Inadequate organ function as evidenced by peripheral blood counts at enrolment: Electrocardiogram (ECG) evidence of uncontrolled cardiac arrhythmias, angina pectoris, and/or hypertension, history of congestive heart failure, or myocardial infarction within last 6 months. Uncontrolled diabetes mellitus. Active uncontrolled gastro-oesophageal reflux disease (GORD). Active infection requiring systemic antibiotic or anti-fungal medication Participation in another clinical trial with any investigational drug within 30 days prior to study enrolment. Concurrent or planned treatment with strong inhibitors of cytochrome P450 3A4/5. A 1-week washout period is necessary for patients who are already on these treatments. Concurrent or planned treatment with strong inducers of cytochrome P450 3A4/5. A 1-week washout period is necessary for patients who are already on these treatments. Contraindications to cisplatin. Patient with reproductive potential not implementing an accepted and effective method of contraception.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cabazitaxel + Cisplatin chemotherapy<br>Cabazitaxel 15mg/m2 Intravenous (IV)followed by Cisplatin 70mg/m2 IV on day 1 of each 21 day cycle for 4 cycles | Drug: Cabazitaxel + Cisplatin chemotherapy<br>* Cabazitaxel 15mg/m2 followed by cisplatin 70mg/m2 given intravenously on day 1 of each 3 weekly cycle for 4 cycles prior to radical cystectomy.<br>* Other names: Jevtana;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall pathological response rate |  | Histological assessment of radical cystectomy specimen expected to be 15 weeks after commencing study chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To record progression free survival | From date of registration until the date of first documented progression or date of death from any cause whichever came first. | Up to 5 years following radical cystectomy | 
| To assess quality of life | EQ-5D and EORTC QLQC30 and BLM30 will be assessed at baseline and following each cycle of chemotherapy | Up to 13 weeks from baseline | 
| To record side effects and tolerability of treatment | Common toxicity criteria adverse events (CTC AE ) Version 4.03 will be assessed at baseline and following each cycle of chemotherapy | Up to 13 weeks from baseline | 
| Overall survival | From the date of registration to the date of death from any cause. | Up to 5 years following radical cystectomy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bladder cancer, Transitional cell carcinoma, Urothelial cancer, Cisplatin, Cabazitaxel, Chemotherapy, Neo adjuvant chemotherapy