University of Birmingham, Cancer Research UK Clinical Trials Unit, School of Cancer Sciences, Birmingham ; 3. ... signif
BILCAP
BILCAP
BILCAP: A randomized clinical trial evaluating adjuvant chemotherapy with capecitabine compared to expectant treatment alone following curative surgery for biliary tract cancer ISCRTN No. 72785446, EUDRACT No. 2005-003318-13 J.A. Bridgewater1. C. Stubbs2, D.D. Stocken2, R.P. Fox2, J.N. Primrose3
Introduction/ Abstract BILCAP is a multi-centre prospective, randomised phase III trial investigating the role of adjuvant chemotherapy with oral fluoropyrimidine (capecitabine) in patients following potentially curative surgical resection of a biliary tract cancer. BILCAP is a multicentre prospective, randomised phase III trial investigating the role of adjuvant chemotherapy with oral fluoropyrimidine (capecitabine) in patients following potentially curative surgical resection of a biliary tract cancer. Patients who have undergone macroscopically complete surgical resection are randomised to receive either adjuvant chemotherapy with capecitabine or observation.
Background
Biliary tract tumours are relatively rare, accounting for 0.7% of malignant tumours in adults, with approximately 1200 new cases registered each year in England and Wales. The 1-year and 5-year survival is poor at 22% and 9% respectively (Cancer Survival Trends in England and Wales 1971 – 1995). Approximately 15-20% of cases are suitable for surgical resection but the outlook remains poor with survival at 5 years approximately 15% (Cancer Survival Trends in England and Wales 1971 – 1995 Most tumours are advanced at presentation and are unsuitable for surgical resection. The BILCAP study, developed by the Hepatobiliary group of the NCRI Upper GI Clinical Studies Group, was designed to determine the benefit of adjuvant therapy following surgery. As such it aims to deliver a key NCRN objective, practise changing outcomes in uncommon cancers. Funding was approved by Cancer Research UK in March 2005 for a phase III, non-commercial trial in patients with resectable biliary tract cancer.
Study Recruitment
Trial Design Patients with Macroscopically resected biliary tract cancer
Main Inclusion Criteria Patients with histologically confirmed: intrahepatic cholangiocarcinoma
Trial recruitment,, remains very strong. 225
With approximately 200 resections for biliary tract cancer per year in the UK, BILCAP has recruited more than 25% of all resected patients in the UK for the last 3 years and 36% in 2010 (51pts in 2008, 53 pts in 2009 and 73 patients in 2010). Recruitment in 2011 currently is on target to surpass the number of patients recruited in 2010.
extrahepatic/hilar cholangiocarcinoma Randomise 360 Patients
of 360 patients have been successfully recruited to date.
350
7
Current Patient Recruitment
lower common bile duct cholangiocarcinoma
300
6
Projected Accrual 50 pts per year
Control Arm: Observation 180 Patients
Treatment Arm: Capecitabine Total of 8 cycles 1250mg/m2 180 Patients
Radical and macroscopically complete surgery which includes liver resection, pancreatic resection or, less commonly, both. ECOG Performance Status < 2
Number of patients
muscle invasive gallbladder cancer
Adequate renal, haematological and liver function On Relapse: Treatment as indicated
Year2006
5
Year2007 4
The primary outcome measure is overall survival . To detect an increase in 2 year survival from 20 to 32%, with 2-sided significance level of 5% and 80% power, 360 patients (270 events) are to be randomised
Year2009 100
2
Year2010 Year 2011
Mar-06 Jun-06 Sep-06 Dec-06 Mar-07 Jun-07 Sep-07 Dec-07 Mar-08 Jun-08 Sep-08 Dec-08 Mar-09 Jun-09 Sep-09 Dec-09 Mar-10 Jun-10 Sep-10 Dec-10 Mar-11 Jun-11 Sep-11 Dec-11 Mar-12 Jun-12 Sep-12 Dec-12 Mar-13 Jun-13 Sep-13 Dec-13 Mar-14
Main Exclusion Criteria
Mucosal gallbladder cancer Incomplete recovery from previous surgery or unresolved biliary tree obstruction
Survival and Toxicity At the time of this interim analysis 41 (18%) patients had died within 24 months. Median FU of alive patients is 9.3 (IQR 2.8, 18.5) months and as such the survival curves are not stable beyond this time point. 12 month survival rate of 86.4% (95%CI 79.6, 91.0) at the time of this interim analysis.
BILCAP Outcome Measures Primary • Overall Survival
Secondary • • • •
Relapse free survival Toxicity Quality of life (QoL) Health economics
BILCAP Timelines • First centre opened March 2006 • 1st patient recruited July 2006
Overall Survival (%)
100.00
Any previous chemotherapy or radiotherapy for biliary tract cancer
75.00 50.00 25.00 0.00
• Accrual completion Q1 2013
0
6
12 Months
18
24
225
150
97
63
33
Number at risk
• Primary analysis 2015
50 0
Mean monthly accrual for BILCAP per year
Pancreatic or ampullary cancer
200 150
3
0
Aims and Objectives
Projected Accrual 75 pts per year
Year2008
1
Age 18 years or over
250
100 (Capecitabine) patients have returned 571 treatment forms No grade 4 toxicities observed to date Toxicities within expected levels Hand-foot and GI toxicities most prevalent, as anticipated
Toxicity Fatigue Fever Weight loss Hand-foot reaction Diarrhea Mucositis/stomatitis Nausea Vomiting Other
Grades 1&2 Grades 3&4* % pts % pts 71% 13% 13% 0% 13% 0% 65% 15% 54% 10% 41% 1% 48% 1% 20% 0% 60% 16%
Overall 84% 13% 13% 80% 64% 42% 49% 20% 76%
Conclusions BILCAP is the most successful adjuvant study in biliary tract cancer and is on target to complete accrual early in 2013. The main focus for the Trials Management Group is to demonstrate the relative success in the UK and open the trial internationally. The results of BILCAP will define the international standard of care for patients with resected biliary tract cancer. 1.UCL, UCL Cancer Institute, London, UK ; 2. University of Birmingham, Cancer Research UK Clinical Trials Unit, School of Cancer Sciences, Birmingham ; 3. Southampton General Hospital, University Surgical Unit, Southampton, UK. There are no conflicts of interest listed for any of the authors
