Clinical trial NCT00262769: Gemcitabine With or Without Cisplatin in Treating Patients With Unresectable Locally Advanced or Metastatic Cholangiocarcinoma or Other Biliary Tract Tumors
Official title: Gemcitabine, Alone or in Combination With Cisplatin, in Patients With Advanced or Metastatic Cholangiocarcinomas and Other Biliary Tract Tumors: A Multicentre, Randomized Phase III Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Extrahepatic Bile Duct Cancer
Gallbladder Cancer
Keywords: cholangiocarcinoma of the extrahepatic bile duct
recurrent extrahepatic bile duct cancer
unresectable extrahepatic bile duct cancer
cholangiocarcinoma of the gallbladder
recurrent gallbladder cancer
unresectable gallbladder cancer
metastatic extrahepatic bile duct cancer
metastatic gallbladder cancer
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
First posted: 2005-12-07
Enrollment: 324
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known whether gemcitabine is more effective with or without cisplatin in treating cholangiocarcinoma or biliary tract tumors.

PURPOSE: This randomized phase III trial is studying gemcitabine and cisplatin to see how well they work compared to gemcitabine alone in treating patients with unresectable locally advanced or metastatic cholangiocarcinoma or other biliary tract tumors.

Detailed description: OBJECTIVES:

Primary

* Compare the overall survival of patients with unresectable locally advanced or metastatic cholangiocarcinoma or other biliary tract tumors treated with gemcitabine hydrochloride with vs without cisplatin.

Secondary

* Compare the progression-free survival of patients treated with these regimens.
* Compare the toxic effects of these regimens in these patients.
* Compare quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, primary site of disease (gallbladder vs bile ducts vs ampulla), prior therapy (photodynamic therapy \[PDT\] vs non-PDT therapy vs none), ECOG performance status (0 vs 1 vs 2), and disease status (locally advanced vs metastatic). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 1½ hours on days 1 and 8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, 12 weeks, and after finishing treatment.

After completion of study treatment, patients are followed periodically for at least 3 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 400 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed biliary tract, gallbladder, or ampullary carcinoma

  * Intra- or extra-hepatic disease allowed
* Unresectable locally advanced, recurrent, or metastatic disease
* No brain metastases

PATIENT CHARACTERISTICS:

Performance status

* ECOG 0-2

Life expectancy

* At least 3 months

Hematopoietic

* Absolute neutrophil count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Hemoglobin ≥ 10 g/dL (transfusion allowed)
* WBC ≥ 3,000/mm\^3

Hepatic

* AST and ALT ≤ 3 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
* Bilirubin ≤ 1.5 times ULN
* Alkaline phosphatase ≤ 3 times ULN (5 times ULN if liver metastases are present)
* Adequate biliary drainage
* No unresolved biliary tract obstruction

Renal

* Creatinine \< 1.5 times ULN
* Urea \< 1.5 times ULN
* Glomerular filtration rate (GFR) ≥ 45 mL/min

  * If GFR \< 60 mL/min, isotope EDTA confirmation of adequate renal function is required

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 3 months after study participation
* No active, uncontrolled infection
* No other severe or uncontrolled systemic disease
* No other malignancy within the past 5 years except nonmetastatic basal cell or squamous cell skin cancer or carcinoma in situ of the cervix treated by cone-biopsy or resection
* No psychiatric disorder that would preclude giving informed consent

PRIOR CONCURRENT THERAPY:

Chemotherapy

* At least 6 months since prior adjuvant chemotherapy
* No prior gemcitabine hydrochloride
* No prior cisplatin
* No prior systemic chemotherapy for locally advanced or metastatic disease except low-dose radiosensitizing chemotherapy in conjunction with radiotherapy

Radiotherapy

* Prior radiotherapy for localized disease allowed provided there is clear evidence of disease progression afterwards

Surgery

* Prior curative surgery allowed provided there is evidence of nonresectable disease relapse requiring systemic chemotherapy

Other

* Recovered from all prior therapies
* Prior photodynamic therapy (PDT) allowed provided it was given for localized disease only (with no evidence of metastatic disease) and resulted in subsequent disease progression after completion of therapy OR to relieve biliary obstruction in the presence of metastatic disease

  * PDT must have been completed ≥ 4 weeks ago
* At least 4 weeks since prior investigational agents
* No other concurrent, curative anticancer therapy

Primary outcomes:
measure: Overall Survival
timeFrame: From date of randomisation till date of death or last date of follow-up (up to 5 years)
Secondary outcomes:
measure: Progression-free survival
timeFrame: From date of randomisation till date of death or last date of follow-up (up to 5 years)
measure: Quality of life
timeFrame: Before and 12 weeks after completion of treatment
measure: Toxicity
timeFrame: During treatment and follow-up
Other outcomes:
Locations:
city: Basingstoke
country: United Kingdom
facility: Basingstoke and North Hampshire NHS Foundation Trust
state: England
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Carlisle
country: United Kingdom
facility: Cumberland Infirmary
state: England
city: Cheltenham
country: United Kingdom
facility: Gloucestershire Oncology Centre at Cheltenham General Hospital
state: England
city: Derby
country: United Kingdom
facility: Derbyshire Royal Infirmary
state: England
city: Essex
country: United Kingdom
facility: Princess Alexandra Hospital
state: England
city: Gloucester
country: United Kingdom
facility: Gloucestershire Royal Hospital
state: England
city: Hull
country: United Kingdom
facility: Princess Royal Hospital at Hull and East Yorkshire NHS Trust
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University 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: Royal Marsden - London
state: England
city: London
country: United Kingdom
facility: Hammersmith Hospital
state: England
city: London
country: United Kingdom
facility: UCL Cancer Institute
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: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology
state: England
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre at Mount Vernon Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
state: England
city: Portsmouth Hants
country: United Kingdom
facility: Portsmouth Oncology Centre at Saint Mary's Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Belfast
country: United Kingdom
facility: Belfast City Hospital Trust Incorporating Belvoir Park Hospital
state: Northern Ireland
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
city: Rhyl, Denbighshire
country: United Kingdom
facility: Glan Clwyd Hospital
state: Wales
Study officials:
affiliation: University College London (UCL) Cancer Institute
name: John A. Bridgewater
role: STUDY_CHAIR
References:
citation: Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. doi: 10.1056/NEJMoa0908721.