Bristol Bladder Trial
Research type
Research Study
Full title
A Phase II Trial of Combination Cabazitaxel and Cisplatin Chemotherapy in the Neoadjuvant Treatment of Transitional Cell Carcinoma of the Urinary Bladder
IRAS ID
87941
Contact name
Amit Bahl
Sponsor organisation
University Hospitals Bristol NHS Foundation Trust Research and Innovation Department
Eudract number
2011-004090-82
Research summary
Summary of Research
This is a phase 2 study, of 26 patients undergoing radical (curative) treatment for invasive bladder cancer. Its aim is to evaluate the proportion of patients whose disease responds to a new combination of chemotherapy drugs (Cisplatin and Cabazitaxel) given before surgery to remove the bladder. Some patients with bladder cancer are cured with existing treatments, but a proportion will develop persistent or recurrent cancer which can spread to other parts of the body. The existing standard treatment is chemotherapy with cisplatin, in combination with one or more other chemotherapy drugs, before surgery. Chemotherapy has been shown in large studies to improve life expectancy and long term cure rate, albeit by a small amount. However, it is not clear which drug or drugs are the most effective in combination with cisplatin. Cabazitaxel is a chemotherapy which improves survival in other cancers, even in advanced stages. It belongs to a drug family, taxanes, several of which can be effective treatments for invasive bladder cancer. Cabazitaxel has been studied in combination with Cisplatin in cancer patients and the doses being used in this trial are known to be safe. There is no reason to suspect that this combination would be less effective than existing treatments. It is hoped that this will lead to a larger Phase 3 trial, which will establish whether cabazitaxel and cisplatin are better than existing standard chemotherapy. Patients in this chemotherapy trial will also be offered 3 MRI scans and 5 blood tests to measure circulating tumour cells (CTCs) before and during their chemotherapy, with the aim of assessing whether MRI and/or CTC measurement are useful tools for predicting which patients will respond well to chemotherapy. MRI scans and CTC blood tests are optional and comprise two sub studies of the main trial.
Summary of results
The Bristol Bladder Trial - A Phase II Trial of Combination Cabazitaxel and Cisplatin Chemotherapy in the Neoadjuvant Treatment of Transitional Cell Carcinoma of the Urinary BladderIntroduction
The Bristol Bladder Trial looked at how well cabazitaxel and cisplatin worked for bladder cancer before surgery to remove it. The trial recruited 28 patients with muscle-invasive bladder cancer. This is where the tumour has grown into or through the muscle wall of the bladder but has not spread to any other parts of the body including any lymph nodes. These patients all had treatment intended to cure their cancer. First they were given chemotherapy, called neoadjuvant chemotherapy as it is given before their surgery. This was then followed by surgery to remove their bladder.
The current standard neoadjuvant chemotherapy is cisplatin plus 1 or more other chemotherapy drugs. Research has shown that having this neoadjuvant chemotherapy plus surgery is better than having surgery only. It increases the number of patients who no longer have any detectable cancer once surgery has been completed, lowers the risk of the cancer coming back and improves survival rates, the number of years patients live after diagnosis. In this study we gave patients cisplatin plus the chemotherapy drug cabazitaxel. Patients had up to 4 cycles of neoadjuvant chemotherapy before surgery. Each cycle was scheduled to last 21 days with treatment given on the first day of each cycle.
The main aims of the trial were to find out how well this drug combination works and learn more about possible side effects.
Results
We found that 58% of patients (15 out of 26) had a response to the chemotherapy (their tumour shrunk) with the tumour disappearing in over a third of patients (35%). This compared favourably with cisplatin plus gemcitabine, the most commonly used combination of drugs, where the tumour disappeared in only a quarter of patients (26%).
In those patients who showed a response to the neoadjuvant chemotherapy nearly all of them (93%), were cancer free 5 years after surgery and 93% were still alive.
For half the patients whose cancer did not respond to the neoadjuvant chemotherapy, the cancer came back after about 7.2 months and their survival rate was 20.5 months (time after surgery when half these patients were still alive). At 5 years after surgery 36% were still alive.
Overall, 65% of patients on the trial were still alive 5 years after surgery.
Patients on cisplatin plus cabazitaxel did suffer adverse events (side effects) while on treatment. However, these were not unusual for this type of chemotherapy and the combination of cisplatin plus cabazitaxel did not raise any safety concerns. The most common side effects were:
• Feeling or being sick
• Constipation
• Tummy pain
• Tiredness (fatigue)Most of the patients (78%) completed all 4 cycles of chemotherapy with only a few needing to either delay their chemotherapy or reduce the dose due to side effects.
Additionally having this neoadjuvant chemotherapy did not stop patients having surgery or prolong the recovery time from surgery.
Patients completed questionnaires about their quality of life before, during and after cisplatin plus cabazitaxel. The results showed an increase in side effects on treatment and a drop in several areas of patient reported quality of life after the first cycle of treatment. However, after cycle 1 there was no further decrease in patient quality of life scores with subsequent cycles. Overall health scores from before treatment began did not change significantly during the trial treatment. These patient reported outcomes suggest that cisplatin plus cabzitaxel is a well-tolerated chemotherapy combination.
Conclusion
The trial only looked at a small number of patients but the results have shown that cisplatin plus cabaitaxel is an effective neoadjuvant chemotherapy and is well tolerated. Further evaluation of cisplatin plus cabaitaxel as a neoadjuvant chemotherapy treatment for this patient group is therefore warranted.
REC name
South West - Central Bristol Research Ethics Committee
REC reference
11/SW/0345
Date of REC Opinion
6 Feb 2012
REC opinion
Further Information Favourable Opinion