Condition category
Cancer
Date applied
13/09/2005
Date assigned
17/11/2005
Last edited
24/03/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Prof John Primrose

ORCID ID

Contact details

University Surgical Unit
F Level
Centre Block
Southampton General Hospital
Southampton
SO16 6YD
United Kingdom

Additional identifiers

EudraCT number

2005-003318-13

ClinicalTrials.gov number

NCT00363584

Protocol/serial number

HE3002

Study information

Scientific title

A randomised clinical trial evaluating adjuvant chemotherapy with capecitabine compared to expectant treatment alone (observation), following surgical resection of a biliary tract tumour

Acronym

BILCAP

Study hypothesis

To evaluate adjuvant chemotherapy with capecitabine in patients who have undergone complete macroscopic resection of a biliary tract cancer. The primary objective is to determine 2-year survival in patients treated with capecitabine compared to those undergoing observation. The secondary objectives are to compare 5-year survival, relapse-free interval, toxicity, quality of life and healthcare economics.

On 09/02/10 the inclusion and exclusion criteria for this trial were updated. Please see the relevant field for more details. Please also note that the anticipated end date of this trial was extended from 01/10/2008 to 01/03/2011.

Ethics approval

West Midlands Ethics Committee, 04/10/2005, ref: 05/MRE07/62

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Biliary tract cancer

Intervention

Current interventions as of 24/03/2017:
This is a multicentre, prospective, randomised phase III trial of patients who have undergone a macroscopically complete surgical resection of a biliary tract cancer. Those patients who fulfil the inclusion criteria are stratified by surgical centre, tumour site (hilar/extrahepatic cholangiocarcinoma, intrahepatic cholangiocarcinoma, lower common bile duct cholangiocarcinoma and gall bladder carcinoma), and by the type of resection (RO/R1) and performance status (ECOG PS 0,1,2), and randomised to either:

Treatment arm: Capecitabine 1250 mg/m2 given post-operatively twice a day on day 1 to 14 of a 3 weekly cycle for 24 weeks (8 cycles).

Control arm: No scheduled post-operative chemotherapy.

A total of 447 patients who have undergone a macroscopically complete surgical resection of a biliary tract cancer will be randomised equally into each arm of the study, and will be followed-up for 5 years.

Previous interventions:
A randomised phase III study of adjuvant chemotherapy with capecitabine compared to expectant treatment alone (observation) in patients following surgical resection of a biliary tract tumour.

Intervention type

Drug

Phase

Phase III

Drug names

Capecitabine

Primary outcome measures

2-year survival

Secondary outcome measures

Current secondary outcome measures as of 24/03/2017:
1. 5-year survival
2. Relapse is measured by 3 monthly follow up visits for 1st year, 6 monthly follow up visits for 2nd year and annual visits for up to 5 years from randomisation. 6 monthly CT scans (chest/abdo/pelvis) for first two years and then annually for up to 5 years from randomisation
3. Toxicity is measured on Day 1 of every treatment cycle and at the end of treatment (within 4 weeks of last treatment administered). Long-term toxicities are measured during follow up visits 3 monthly follow up visits for 1st year, 6 monthly follow up visits for 2nd year and annual visits for up to 5 years from randomisation
4. Quality of life is assessed using EORTC QoL questionnaire (QLQ-C30 ) version 3 with the EORTC QLQ-LMC21 site-specific add-on and EuroQoL (5 questions). QOL is measured at baseline, 3 monthly for the 1st year and 6 monthly for the 2nd year
5. Healthcare economics to assess the relative cost effectiveness of the treatment regimes (chemotherapy or observation) for the duration of treatment and for the first two years of follow-up, using the same sub-set of QoL patients. The collection of the data for the economic evaluation is collected by adding the health problems questionnaire (5 questions) -to the QOL booklet to ascertain the resource use.

Previous secondary outcome measures:
1. 5-year survival
2. Relapse
3. Toxicity
4. Quality of life
5. Healthcare economics

Overall trial start date

01/01/2005

Overall trial end date

31/12/2020

Reason abandoned

Eligibility

Participant inclusion criteria

Current information as of 09/02/2010 (update to trial made in December 2008)
1. Patients with histologically confirmed biliary tract cancer (including intrahepatic cholangiocarcinoma, extrahepatic/hilar cholangiocarcinoma, muscle invasive gallbladder cancer or cancer of the distal bile duct) who have undergone a macroscopically complete resection with curative intent.
2. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
3. Age > 18
4. Adequate renal function:
4.1. Serum urea and serum creatinine < 1.5 times upper limit of normal (ULN)
4.2. Calculated glomerular filtration rate (GFR) using Cockcroft-Gault ≤ 60 ml/min. If the calculated GFR is below 60 ml/min, isotope EDTA confirmation of adequate renal function (as detailed in the Summary of Product Characteristics [SPC] for capecitabine) is required
5. Adequate haematological function:
5.1. Haemoglobin ≥ 10g/dl
5.2. WBC ≥ 3.0 x 109/L
5.3. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
5.4. Platelet count ≥ 100,000/mm3
6. Adequate liver function:
6.1. Total bilirubin ≤ 3 x ULN
6.2. Alanine transaminase (ALT) or aspartate transaminase (AST) ≤ 5 x ULN
6.3. Adequate surgical biliary drainage with no evidence of infection
7. Not of childbearing potential OR must be using an approved method of contraception
8. Written informed consent
9. Able to start treatment within 12 weeks of surgery. If the treatment start date is >12 weeks, it will be necessary to contact the BILCAP Trial Office.

Current information as of 28/02/2008:
1. Age 18 or over
2. Histologically confirmed biliary tract cancer (including intrahepatic or extrahepatic cholagiocarcinoma or muscle-invasive gallbladder cancer) and undergone macroscopically complete resection with curative intent
3. No history of other malignant diseases (other than adequately treated non-melanotic skin cancer or in situ carcinoma of the uterine cervix)
4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
5. Adequate renal function (serum urea and serum creatinine less than 1.5 times upper limit of normal [ULN], glomerular filtration rate greater than/equal to 60 ml/min). If the calculated GFR is below 60 ml/min, isotope EDTA confirmation of adequate renal function (as detailed in the Summary of Product Characteristics [SPC] for capecitabine)
6. Adequate haematological function (haemoglobin =10 g/dl, white blood cells [WBC] =3.0 x 10^9/l, absolute neutrophil count [ANC] =1.5 x 10^9/l, platelet count =100,000/mm^3)
7. Adequate liver function (total bilirubin ≤3 x ULN, alanine aminotransferase [ALT] or aspartate aminotransferase [AST] ≤5 times ULN, adequate surgical biliary drainage with no evidence of infection)
8. Not of childbearing potential OR must be using an approved method of contraception
9. Written informed consent

Information at time of registration:
1. Age 18 or over
2. Histologically confirmed biliary tract cancer (including intrahepatic or extrahepatic cholagiocarcinoma or muscle-invasive gallbladder cancer) and undergone macroscopically complete resection with curative intent
3. No history of other malignant diseases (other than adequately treated non-melanotic skin cancer or in situ carcinoma of the uterine cervix)
4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
5. Adequate renal function (serum urea and serum creatinine less than 1.5 times upper limit of normal [ULN], glomerular filtration rate greater than/equal to 60 ml/min)
6. Adequate haematological function (haemoglobin =10 g/dl, white blood cells [WBC] =3.0 x 10^9/l, absolute neutrophil count [ANC] =1.5 x 10^9/l, platelet count =100,000/mm^3)
7. Adequate liver function (total bilirubin less than 50 µmol/l, alanine aminotransferase [ALT] or aspartate aminotransferase [AST] = 5 times ULN, adequate surgical biliary drainage with no evidence of infection)
8. Not of childbearing potential OR must be using an approved method of contraception
9. Written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

360

Participant exclusion criteria

Current information as of 09/02/2010 (update to trial made in December 2008):
1. Pancreatic or ampullary cancer or mucosal gallbladder cancer
2. Incomplete recovery from previous surgery or unresolved biliary tree obstruction
3. Use of other investigational agents during the study treatment period, or within 4 weeks of planned entry to the study
4. History of other malignancy within 5 years of trial entry, except adequately treated cervical carcinoma-in-situ or non-melanotic skin cancer.
5. Any previous chemotherapy or radiotherapy, given for biliary tract cancer.
6. A serious co-existing medical condition likely to interfere with protocol treatment including a potential serious infection.
7. Evidence of significant clinical disorder or laboratory finding which, in the opinion of the investigator, makes it undesirable for the patient to participate in the trial

Information at time of registration:
1. Pancreatic or periampullary cancer or mucosal gallbladder cancer
2. Resection of tumour that involved the pancreas
3. Incomplete recovery from previous surgery or unresolved biliary tree obstruction
4. Use of other investigational agents during the study or within 4 weeks of planned entry to the study
5. Previous chemotherapy, radiotherapy, biological or hormone therapy given for biliary tract cancer
6. History of second malignancy within 5 years of trial entry, except non-melanotic skin cancer or in situ cervical carcinoma
7. A serious co-existing medical condition including a potential serious infection
8. Evidence of significant clinical disorder or laboratory finding which, in the opinion of the investigator, makes it undesirable for the patient to participate in the trial
9. Psychological, familial, sociological or geographical factors considered likely to prevent compliance with the protocol
10. Any other serious uncontrolled medical conditions
11. Pregnant or breastfeeding women

Recruitment start date

10/07/2006

Recruitment end date

04/12/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Southampton General Hospital (Lead Centre)
University Surgical Unit Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

Addenbrooke's Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Basildon & Thurrock University Hospital
Nethermayne Essex
Basildon
SS16 5NL
United Kingdom

Trial participating centre

Basingstoke and North Hampshire Hospital
Aldermaston Road
Basingstoke
RG24 9NA
United Kingdom

Trial participating centre

Beatson West of Scotland Cancer Centre
1053 Gt. Western Road
Glasgow
G12 0YN
United Kingdom

Trial participating centre

Bristol Haematology And Oncology Centre
Horfield Road
Bristol
BS2 8ED
United Kingdom

Trial participating centre

Christie Hospital
Wilmslow Road Withington
Manchester
M20 4BX
United Kingdom

Trial participating centre

Clatterbridge Cancer Centre
Clatterbridge Road Wirral
Bebington
CH63 4JY
United Kingdom

Trial participating centre

Derriford Hospital
Derriford Road Crownhill
Plymouth
PL6 8DH
United Kingdom

Trial participating centre

Freeman Hospital
Freeman Road High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom

Trial participating centre

Hammersmith Hospital
Du Cane Road
London
W12 0HS
United Kingdom

Trial participating centre

Huddersfield Royal Infirmary
Lindley
Huddersfield
HD3 3EA
United Kingdom

Trial participating centre

James Paget Hospital
Lowestoft Road Gorleston Great Yarmouth
Norfolk
NR31 6LA
United Kingdom

Trial participating centre

Leicester General Hospital
Gwendolen Road
Leicester
LE5 4PW
United Kingdom

Trial participating centre

Leicester Royal Infirmary
Leicester
LE1 5WW
United Kingdom

Trial participating centre

Maidstone Hospital
Hermitage Lane Kent
Maidstone
ME16 9QQ
United Kingdom

Trial participating centre

Ninewells Hospital
Dundee
DD1 9SY
United Kingdom

Trial participating centre

North Manchester General Hospital
Delaunays Road
Manchester
M8 5RB
United Kingdom

Trial participating centre

North Middlesex Hospital
Sterling Way
London
N18 1QX
United Kingdom

Trial participating centre

Nottingham City Hospital
Hucknall Road
Nottingham
NG5 1PB
United Kingdom

Trial participating centre

Poole Hospital
Longfleet Road Dorset
Poole
BH15 2JB
United Kingdom

Trial participating centre

Princess Alexandra Hospital
Hamstel Road
Harlow
CM20 1QX
United Kingdom

Trial participating centre

Queen Alexandra Hospital
Southwick Hill Road
Portsmouth
PO6 3LY
United Kingdom

Trial participating centre

Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom

Trial participating centre

Royal Bournemouth Hospital
Castle Lane East
Bournemouth
BH7 7DW
United Kingdom

Trial participating centre

Royal Derby Hospital
Uttoxeter Road
Derby
DE22 3NE
United Kingdom

Trial participating centre

Royal Free Hospital
Pond Street
London
NW3 2QG
United Kingdom

Trial participating centre

Royal Liverpool University Hospital
Prescot Street
Liverpool
L7 8XP
United Kingdom

Trial participating centre

Royal Marsden Hospital London
Fulham Road
London
SW3 6JJ
United Kingdom

Trial participating centre

Royal Marsden Hospital Sutton
Downs Road
Sutton
SM2 5PT
United Kingdom

Trial participating centre

Royal Surrey County Hospital
Egerton Road
Guildford
GU2 7XX
United Kingdom

Trial participating centre

Salisbury District Hospital
Salisbury
SP2 8BJ
United Kingdom

Trial participating centre

Southend University Hospital
Pritilewell Chase
Westcliff on Sea
SS0 0RY
United Kingdom

Trial participating centre

St Bartholomew's Hospital
West Smithfield
London
EC1A 7BE
United Kingdom

Trial participating centre

St James's University Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom

Trial participating centre

St Mary's Hospital
Parkhurst Road
Newport
PO30 5TG
United Kingdom

Trial participating centre

St Thomas's Hospital
St Thomas Street
London
SE1 9RT
United Kingdom

Trial participating centre

University College London Hospital
250 Euston Road
London
NW1 2PQ
United Kingdom

Trial participating centre

University Hospital Aintree
Lower Lane
Liverpool
L9 7AL
United Kingdom

Trial participating centre

University Hospital Coventry & Warwickshire NHS Trust
Clifford Bridge Road
Coventry
CV2 2DZ
United Kingdom

Trial participating centre

Velindre Hospital
Velindre Road Whitchurch
Cardiff
CF14 2TL
United Kingdom

Trial participating centre

Western General Hospital
Edinburgh
EH4 2XU
United Kingdom

Trial participating centre

Weston Park Hospital
Whitham Road
Sheffield
S10 2SJ
United Kingdom

Trial participating centre

Yeovil District Hospital
Somerset
BA21 4A
United Kingdom

Sponsor information

Organisation

The University of Southampton

Sponsor details

Legal Services
Building 37
Room 4033
The University of Southampton
Southampton
SO17 1BJ
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

Cancer Research UK (CRUK) (UK) (Ref: C317/A4273)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

An abstract of the trial results has been submitted to ASCO 06/02/2017. A publication in a high-impact peer reviewed journal is planned for 2017.

IPD sharing plan:
The datasets generated during and/or analysed during the current study are/will be available upon request from BILCAP@trials.bham.ac.uk

Intention to publish date

31/12/2017

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

24/03/2017: Updated public title, ethics and outcome measures. Overall trial dates changed from 01/03/2006 - 01/03/2011 to 01/01/2005 - 31/12/2020. Recruitment dates changed from 01/03/2006 - 01/03/2011 to 10/07/2006 - 04/12/2014. Added trial participating sites. 20/03/2017: No publications found in PubMed, verifying study status with principal investigator.