Bristol Bladder trial
21 February 2018
A Phase II Trial of combination Cabazitaxel and Cisplatin Chemotherapy in the Neoadjuvant Treatment of Transitional Cell Carcinoma of the Urinary Bladder.
This study, under Chief Investigator Dr Amit Bahl, has reached its primary endpoint (with the final patient successfully undergoing surgery last week) and 2 out of 3 of its secondary endpoints.
- To evaluate the overall response rate with this chemotherapy regimen in the neoadjuvant treatment of transitional cell carcinoma of the bladder and thus determine whether this approach warrants further research (randomised Phase II/ III trial).
- To evaluate safety and tolerability
- To assess progression-free and overall survival; patients in follow up
- To assess quality of life during treatment
The Bristol Bladder study presented a poster at the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium held in San Francisco, USA, 8 - 10 February 2018. Entitled The Bristol Bladder trial: A single-arm phase II trial of cisplatin and cabazitaxel for muscle invasive transitional cell carcinoma of the urinary bladder prior to radical cystectomy, the poster was presented on 9 February 2018.
Neoadjuvant cisplatin-based combination chemotherapy improves survival in muscle invasive transitional cell carcinoma (MI-TCC). However response rates and survival remain suboptimal. We sought to evaluate the efficacy of cabazitaxel (CBZ) with cisplatin (CIS) in this setting.
A single arm phase 2 study was designed with 80% power to detect an objective response rate (ORR) of >35%. Patients with MI-TCC were included if fit to receive neoadjuvant chemotherapy and to undergo radical cystectomy. Treatment was with CIS 70mg/m2 and CBZ 15mg/m2 on day 1 of a 21 day cycle, for 4 cycles prior to surgery. Primary prophylaxis was with pegylated GCSF. Toxicity was recorded using CTCAE v.4.03. Objective response was defined as a reduction in Tumour (T) stage from T2 or greater at diagnosis, to T1 or less at radical cystectomy. QoL data was assessed during and after chemotherapy using EQ-5D and EORTC-BLM30 questionnaires.
28 patients were enrolled with median age 68.6 years (range 47-79). Response outcome (first 23 cases) and toxicity data (first 24 cases) are in this abstract; the remaining cases, currently scheduled for surgery, will be added to the final presentation. Pathological complete response (pCR) was observed in 7/23 patients (30.4%) and ORR was 56.5% (13/23). 18/24 (75%) completed 4 cycles; reasons for stopping were disease progression (2/24, 8.3%), adverse events (2/24, 8.3%) and patient choice (2/24, 8.3%). 7/24 patients (29%) experienced treatment related grade 3 and 4 adverse events.
These results demonstrate that CIS and CBZ chemotherapy has an acceptable safety profile and is well tolerated in this setting. This combination shows promising efficacy (pCR 30.4%, ORR 56.5%) prior to definitive treatment for MI-TCC. Response outcomes for all patients and QoL data will be reported in the final presentation. Grade 3/4 adverse events. Clinical trial information: NCT01616875