Bristol Bladder Trial

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

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.

1. Contrast Magnetic resonance imaging (MRI ) scans will be taken at baseline and after cycle 1 and cycle 3.
2. 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

Study Overview

• Status: Completed
• Conditions: Infiltrating Bladder Urothelial Carcinoma
• Intervention / Treatment: Drug: Cabazitaxel + Cisplatin chemotherapy

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Bristol, United Kingdom, BS2 8ED
    • Bristol Haematology + Oncology Centre, Horfield Road

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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, chemotherapy, 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cabazitaxel + Cisplatin chemotherapy; 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; 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.; Other Names: Jevtana

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Pathological Response Rate	Pathological stage at diagnosis (T2/T3 - see baseline characteristics) was compared to pathological stage of the surgical specimen at cystectomy. A response is considered as a decrease in T stage from T2/T3 seen at baseline to T1 or less indicating a reduction in tumour size/invasiveness. The T stage describes how far the primary tumour has spread. The higher the stage the further the tumour has grown through the bladder wall and into the surrounding tissues. The stages are Ta - non-invasive papillary carcinoma, Tis - flat non-invasive carcinoma, T1 - grown through the connective tissue but not into the muscle of the bladder wall, T2 - tumour has grown through the connective tissue and into the muscle of the bladder wall, T3 - tumour has grown through the muscle and into the fatty layer surrounding the bladder and T4 - the cancer has spread to surrounding tissues.	Histological assessment of radical cystectomy specimen expected to be 15 weeks after commencing study chemotherapy.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival at 5 Years After Cystectomy	From registration until progression or death from any cause up to 5 years after surgery. Outcome is the percentage of patients who are progression free. After cystectomy patients are tumour free. They are reviewed regularly and CT scans and further tests are requested if it is suspected that the tumour has returned. If there is evidence that the tumour has returned or if the patient dies from any cause this is considered to be progression.	From registration up to 5 years after surgery
Progression Free Survival of Patients Who Did Not Show Pathological Downstaging	From registration until progression or death from any cause up to 5 years after surgery. Outcome is the median number of months it takes 50% of patients to show progression. After cystectomy patients are tumour free. They are reviewed regularly and CT scans and further tests are requested if it is suspected that the tumour has returned. If there is evidence that the tumour has returned or if the patient dies from any cause this is considered to be progression.	From registration up to 5 years after surgery
Overall Survival at 5 Years After Cystectomy	From registration until death from any cause up to 5 years after surgery. Outcome is the percentage of patients alive at 5 years after cystectomy.	From registration up to 5 years after cystectomy
Overall Survival of Patients Who Did Not Show Pathological Downstaging	From registration until death from any cause up to 5 years after surgery. Outcome is the median number of months it takes for 50% of patients to die.	From registration up to 5 years after cystectomy
Assessment of EQ-5D-5L Quality of Life	EQ-5D-5L will be assessed at baseline, following each cycle of chemotherapy and at the end of chemotherapy prior to surgery. The patients answer 5 questions which have 5 possible answers from no issue to extreme issue. The answers are given a code, 1, 2, 3, 4 or 5 with 1 for no issue through to 5 for extreme issues which results in a 5 digit 'health state' for that time point. Using a formula this is translated into the 'EQ-5D index value' where 1 is full health and 0 is the worst health. This is what is presented here, the lower the score the worse the quality of life.	Baseline, pre-Cycle 2 (each cycle was 21 days), pre-Cycle 3, pre-Cycle 4, and end of treatment visit (up to 13 weeks)
Assessment of EQ-5D-5L VAS Score	EQ-5D-5L VAS score was assessed at baseline, following each cycle of chemotherapy and at the end of chemotherapy prior to surgery. Patients are asked to score their health on a scale 0-100, the higher the score the better they are feeling	Baseline, pre-Cycle 2 (each cycle was 21 days), pre-Cycle 3, pre-Cycle 4, and end of treatment visit (up to 13 weeks)
Assessment of EORTC QLQ-C30 Score	EORTC QLQ-C30 questionnaire was completed at baseline, following each cycle of chemotherapy and at the end of chemotherapy prior to surgery. Patients are asked to complete 30 questions and a combined summary score between 0-100 is derived from their answers. The higher the score the better their quality of life.	Baseline, pre-Cycle 2 (each cycle was 21 days), pre-Cycle 3, pre-Cycle 4, and end of treatment visit (up to 13 weeks)
Assessment of BLM30 Urinary Score	EORTC BLM30 questionnaire was completed at baseline, following each cycle of chemotherapy and at the end of chemotherapy prior to surgery. Patients are asked to complete questions which are split into 5 categories Urinary, Future perspectives, Bloating/flatulence, Body image and Sexual functioning. Each question has 4 possible answers from 'not at all' scored 1, to 'very much' scored 4. The scores for each different question in a category are combined and an overall score between 0-100 is derived from the answers. The higher the score the worse the symptom. In this outcome the score for the combined urinary questions is shown.	Baseline, pre-Cycle 2 (each cycle was 21 days), pre-Cycle 3, pre-Cycle 4, and end of treatment visit (up to 13 weeks)
Assessment of BLM30 Future Perspectives Score	EORTC BLM30 questionnaire was completed at baseline, following each cycle of chemotherapy and at the end of chemotherapy prior to surgery. Patients are asked to complete questions which are split into 5 categories Urinary, Future perspectives, Bloating/flatulence, Body image and Sexual functioning. Each question has 4 possible answers from 'not at all' scored 1, to 'very much' scored 4. The scores for each different question in a category are combined and an overall score between 0-100 is derived from the answers. The higher the score the worse the symptom. In this outcome the score for the combined future perspectives questions is shown.	Baseline, pre-Cycle 2 (each cycle was 21 days), pre-Cycle 3, pre-Cycle 4, and end of treatment visit (up to 13 weeks)
Assessment of BLM30 Bloating/Flatulence Score	EORTC BLM30 questionnaire was completed at baseline, following each cycle of chemotherapy and at the end of chemotherapy prior to surgery. Patients are asked to complete questions which are split into 5 categories Urinary, Future perspectives, Bloating/flatulence, Body image and Sexual functioning. Each question has 4 possible answers from 'not at all' scored 1, to 'very much' scored 4. The scores for each different question in a category are combined and an overall score between 0-100 is derived from the answers. The higher the score the worse the symptom. In this outcome the score for the combined bloating/flatulence questions is shown.	Baseline, pre-Cycle 2 (each cycle was 21 days), pre-Cycle 3, pre-Cycle 4, and end of treatment visit (up to 13 weeks)
Assessment of BLM30 Body Image Score	EORTC BLM30 questionnaire was completed at baseline, following each cycle of chemotherapy and at the end of chemotherapy prior to surgery. Patients are asked to complete questions which are split into 5 categories Urinary, Future perspectives, Bloating/flatulence, Body image and Sexual functioning. Each question has 4 possible answers from 'not at all' scored 1, to 'very much' scored 4. The scores for each different question in a category are combined and an overall score between 0-100 is derived from the answers. The higher the score the worse the symptom. In this outcome the score for the combined Body Image questions is shown.	Baseline, pre-Cycle 2 (each cycle was 21 days), pre-Cycle 3, pre-Cycle 4, and end of treatment visit (up to 13 weeks)
Assessment of BLM30 Sexual Function Score	EORTC BLM30 questionnaire was completed at baseline, following each cycle of chemotherapy and at the end of chemotherapy prior to surgery. Patients are asked to complete questions which are split into 5 categories Urinary, Future perspectives, Bloating/flatulence, Body image and Sexual functioning. Each question has 4 possible answers from 'not at all' scored 1, to 'very much' scored 4. The scores for each different question in a category are combined and an overall score between 0-100 is derived from the answers. The higher the score the worse the symptom. In this outcome the score for the combined sexual functioning questions is shown.	Baseline, pre-Cycle 2 (each cycle was 21 days), pre-Cycle 3, pre-Cycle 4, and end of treatment visit (up to 13 weeks)

Collaborators and Investigators

• Sponsor: University Hospitals Bristol and Weston NHS Foundation Trust
• Collaborators: Sanofi
• Investigators: Principal Investigator: Amit K Bahl, University Hospitals Bristol and Weston NHS Foundation Trust

Publications and helpful links

General Publications

• Challapalli A, Masson S, White P, Dailami N, Pearson S, Rowe E, Koupparis A, Oxley J, Abdelaziz A, Ash-Miles J, Bravo A, Foulstone E, Perks C, Holly J, Persad R, Bahl A. A Single-arm Phase II Trial of Neoadjuvant Cabazitaxel and Cisplatin Chemotherapy for Muscle-Invasive Transitional Cell Carcinoma of the Urinary Bladder. Clin Genitourin Cancer. 2021 Aug;19(4):325-332. doi: 10.1016/j.clgc.2021.02.001. Epub 2021 Feb 18.

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2012
• Primary Completion (Actual): November 1, 2017
• Study Completion (Actual): January 4, 2023

Study Registration Dates

• First Submitted: May 17, 2012
• First Submitted That Met QC Criteria: June 8, 2012
• First Posted (Estimated): June 12, 2012

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: February 13, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Bladder cancer; Cisplatin; Chemotherapy; Cabazitaxel; Urothelial cancer; Transitional cell carcinoma; Neo adjuvant chemotherapy
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Carcinoma; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Antineoplastic Agents; cabazitaxel
• Other Study ID Numbers: ON/2011/3775; 2011-004090-82 (EudraCT Number)