Infiltrating Bladder Urothelial Carcinoma
Conditions
Keywords
Bladder cancer, Transitional cell carcinoma, Urothelial cancer, Cisplatin, Cabazitaxel, Chemotherapy, Neo adjuvant chemotherapy
Brief summary
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
Interventions
DRUGCabazitaxel + 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.
Sponsors
University Hospitals Bristol and Weston NHS Foundation Trust
Sanofi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Pathological Response Rate | Histological assessment of radical cystectomy specimen expected to be 15 weeks after commencing study chemotherapy. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival at 5 Years After Cystectomy | From registration up to 5 years after surgery | 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. |
| Progression Free Survival of Patients Who Did Not Show Pathological Downstaging | From registration up to 5 years after surgery | 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. |
| Overall Survival at 5 Years After Cystectomy | From registration up to 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. |
| Assessment of EQ-5D-5L 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) | 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. |
| Assessment of EQ-5D-5L VAS Score | Baseline, pre-Cycle 2 (each cycle was 21 days), pre-Cycle 3, pre-Cycle 4, and end of treatment visit (up to 13 weeks) | 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 |
| Assessment of EORTC QLQ-C30 Score | Baseline, pre-Cycle 2 (each cycle was 21 days), pre-Cycle 3, pre-Cycle 4, and end of treatment visit (up to 13 weeks) | 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. |
| Assessment of BLM30 Urinary Score | Baseline, pre-Cycle 2 (each cycle was 21 days), pre-Cycle 3, pre-Cycle 4, and end of treatment visit (up to 13 weeks) | 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. |
| Assessment of BLM30 Future Perspectives Score | Baseline, pre-Cycle 2 (each cycle was 21 days), pre-Cycle 3, pre-Cycle 4, and end of treatment visit (up to 13 weeks) | 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. |
| Assessment of BLM30 Bloating/Flatulence Score | Baseline, pre-Cycle 2 (each cycle was 21 days), pre-Cycle 3, pre-Cycle 4, and end of treatment visit (up to 13 weeks) | 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. |
| Assessment of BLM30 Body Image Score | Baseline, pre-Cycle 2 (each cycle was 21 days), pre-Cycle 3, pre-Cycle 4, and end of treatment visit (up to 13 weeks) | 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. |
| Overall Survival of Patients Who Did Not Show Pathological Downstaging | From registration up to 5 years after cystectomy | 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. |
| Assessment of BLM30 Sexual Function Score | Baseline, pre-Cycle 2 (each cycle was 21 days), pre-Cycle 3, pre-Cycle 4, and end of treatment visit (up to 13 weeks) | 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. |
Countries
United Kingdom
Contacts
PRINCIPAL_INVESTIGATORAmit K Bahl
University Hospitals Bristol and Weston NHS Foundation Trust
Participant flow
Recruitment details
Recruitment took place at a single site, Bristol Haematology and Oncology Centre, Bristol, UK.. First patient was enrolled in July 2012 and the last in August 2017.
Pre-assignment details
None. Screening as per the eligibility criteria. All eligible patients were registered into the trial and received the same treatment.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 66 years |
| Eastern Cooperative Oncology Group (ECOG) performance status ECOG ≤1 | 28 participants |
| Eastern Cooperative Oncology Group (ECOG) performance status ECOG ≥2 | 0 participants |
| eGFR | 73.7 ml/min/1.73m^2 |
| Pathological T stage T2 | 27 Participants |
| Pathological T stage T3 | 1 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 10 / 27 |
| other Total, other adverse events | 26 / 27 |
| serious Total, serious adverse events | 9 / 27 |
Outcome results
None listed