Bristol Bladder Trial

University Hospitals Bristol and Weston NHS Foundation Trust28 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Infiltrating Bladder Urothelial Carcinoma

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: Histological assessment of radical cystectomy specimen expected to be 15 weeks after commencing study chemotherapy.

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.