Clinical trial NCT00363584: Capecitabine or Observation After Surgery in Treating Patients With Biliary Tract Cancer
Official title: A Randomised Clinical Trial Evaluating Adjuvant Chemotherapy With Capecitabine Compared to Expectant Treatment Alone (Observation) Following Surgery for Biliary Tract Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Extrahepatic Bile Duct Cancer
Gallbladder Cancer
Liver Cancer
Keywords: localized resectable adult primary liver cancer
cholangiocarcinoma of the extrahepatic bile duct
cholangiocarcinoma of the gallbladder
adenocarcinoma of the gallbladder
adenocarcinoma with squamous metaplasia of the gallbladder
anaplastic carcinoma of the gallbladder
localized gallbladder cancer
localized extrahepatic bile duct cancer
squamous cell carcinoma of the gallbladder
adult primary cholangiocellular carcinoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-08-15
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving capecitabine after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, the tumor may not need more treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether capecitabine is more effective than observation in treating biliary tract cancer.

PURPOSE: This randomized phase III trial is studying capecitabine to see how well it works compared with observation in treating patients with biliary tract cancer.

Detailed description: OBJECTIVES:

Primary

* To determine whether adjuvant chemotherapy with capecitabine has any effect on 2-year survival compared to expectant treatment alone (observation) in patients who have undergone a macroscopically complete surgical resection of a biliary tract cancer.

Secondary

* To compare capecitabine versus observation in terms of 5-year survival, relapse-free survival, toxicity, quality of life, and health economics.

OUTLINE: This is a multicenter, prospective, randomized study. Patients are stratified according to surgical center, disease site (hilar/extrahepatic cholangiocarcinoma vs intrahepatic cholangiocarcinoma vs gallbladder vs intrapancreatic/common bile duct), type of resection (R0 vs R1), and ECOG performance status (0 vs 1 vs 2). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral capecitabine twice a day on days 1-14. Treatment repeats every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients undergo expectant treatment (observation). Quality of life is assessed at baseline, every 3 months for 1 year, and then every 6 months for 1 year.

All patients are followed for up to 5 years post-randomization.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 360 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed biliary tract cancer (including intrahepatic or extrahepatic/hilar cholangiocarcinoma or muscle invasive gallbladder cancer or cancer of the distal bile duct)

  * Must have undergone a radical surgical approach which includes liver resection, pancreatic resection, or less commonly both
  * Patients with pathological evidence of microscopic involvement of the margins of the excised specimen are eligible as long as resection is macroscopically complete
* Must be able to start treatment within 12 weeks of surgery
* No pancreatic or periampullary cancer
* No mucosal gallbladder cancer

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Urea \< 1.5 times upper limit of normal (ULN)
* Creatinine \< 1.5 times ULN
* Glomerular filtration rate ≥ 60 mL/min (if \< 60 mL/min, adequate renal function for capecitabine must be confirmed by isotope EDTA)
* Hemoglobin ≥ 10 g/dL
* WBC ≥ 3,000/mm³
* Absolute neutrophil count ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Bilirubin ≤ 3 times ULN
* ALT and AST ≤ 5 times ULN
* Adequate surgical biliary drainage with no evidence of infection
* Not pregnant or nursing
* Negative pregnancy test for women of childbearing age and childbearing potential
* Fertile patients must use effective contraception during study treatment and for at least 3 months after study treatment has ended
* Must provide written informed consent
* No history of other malignant diseases within the past 5 years other than adequately treated nonmelanoma skin cancer or in situ carcinoma of the uterine cervix
* No serious co-existing medical condition likely to interfere with protocol treatment, including a potential serious infection
* No evidence of significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the trial
* No psychological, familial, sociological, or geographical factors considered likely to preclude study compliance
* No other serious uncontrolled medical conditions
* No unresolved biliary tree obstruction

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* Completely recovered from prior surgery
* No use of other investigational agents within 28 days prior to and during study treatment
* No prior chemotherapy or radiotherapy for biliary tract cancer
* No other concurrent anticancer chemotherapy, radiotherapy, or investigational agent

Primary outcomes:
measure: Survival at 2 years
Secondary outcomes:
measure: Survival at 5 years
measure: Relapse-free survival
measure: Toxicity
measure: Quality of life
measure: Health economics
Other outcomes:
Locations:
city: Basildon
country: United Kingdom
facility: Basildon University Hospital
state: England
city: Basingstoke
country: United Kingdom
facility: Basingstoke and North Hampshire NHS Foundation Trust
state: England
city: Birmingham
country: United Kingdom
facility: Cancer Research UK Clinical Trials Unit - Birmingham
state: England
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
state: England
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Coventry
country: United Kingdom
facility: Walsgrave Hospital
state: England
city: Essex
country: United Kingdom
facility: Princess Alexandra Hospital
state: England
city: Guildford
country: United Kingdom
facility: St. Luke's Cancer Centre at Royal Surrey County Hospital
state: England
city: Halifax
country: United Kingdom
facility: Calderdale Royal Hospital
state: England
city: Huddersfield, West Yorks
country: United Kingdom
facility: Huddersfield Royal Infirmary
state: England
city: Leeds
country: United Kingdom
facility: Cancer Research UK Clinical Centre at St. James's University Hospital
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: Leicester
country: United Kingdom
facility: Leicester General Hospital
state: England
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
state: England
city: Liverpool
country: United Kingdom
facility: Aintree University Hospital
state: England
city: London
country: United Kingdom
facility: Saint Bartholomew's Hospital
state: England
city: London
country: United Kingdom
facility: Helen Rollason Cancer Care Centre at North Middlesex Hospital
state: England
city: London
country: United Kingdom
facility: UCL Cancer Institute
state: England
city: London
country: United Kingdom
facility: St. Thomas' Hospital
state: England
city: London
country: United Kingdom
facility: King's College Hospital
state: England
city: London
country: United Kingdom
facility: Royal Marsden - London
state: England
city: London
country: United Kingdom
facility: Hammersmith Hospital
state: England
city: London
country: United Kingdom
facility: University College of London Hospitals
state: England
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital
state: England
city: Manchester
country: United Kingdom
facility: North Manchester General Hospital - Penine Actute Hospitals Trust
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Northern Centre for Cancer Treatment at Newcastle General Hospital
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Freeman Hospital
state: England
city: Newport
country: United Kingdom
facility: St. Mary's Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
state: England
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: England
city: Portsmouth Hants
country: United Kingdom
facility: Portsmouth Oncology Centre at Saint Mary's Hospital
state: England
city: Redditch, Worcestershire
country: United Kingdom
facility: Alexandra Healthcare NHS
state: England
city: Salisbury
country: United Kingdom
facility: Salisbury District Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden - Surrey
state: England
city: Westcliff-On-Sea
country: United Kingdom
facility: Southend University Hospital NHS Foundation Trust
state: England
city: Yeovil
country: United Kingdom
facility: Yeovil District Hospital
state: England
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre at Western General Hospital
state: Scotland
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Scotland
city: Perth
country: United Kingdom
facility: Perth Royal Infirmary
state: Scotland
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
Study officials:
affiliation: Cancer Research Campaign Clinical Trials Centre
name: Clive Stubbs
References: