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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
324
25 mg/m2 in 1000 mls 0.9% saline given over 1 hour followed by 500 mls 0.9% saline over 90 mins
1000mg/m2 in 250-500mls 0.9% saline over 30 mins by intravenous infusions on day 1, 8 and 15 (Arm A only) of each 28 (Arm A) or 21 (Arm B) day cycle.
Basingstoke and North Hampshire NHS Foundation Trust
Basingstoke, England, United Kingdom
Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
Birmingham, England, United Kingdom
Addenbrooke's Hospital
Cambridge, England, United Kingdom
Cumberland Infirmary
Carlisle, England, United Kingdom
Gloucestershire Oncology Centre at Cheltenham General Hospital
Cheltenham, England, United Kingdom
Overall Survival
From date of randomisation till date of death or last date of follow-up (up to 5 years)
Time frame: From date of randomisation till date of death or last date of follow-up (up to 5 years)
Progression-free survival
From date of randomisation till date of death or last date of follow-up (up to 5 years)
Time frame: From date of randomisation till date of death or last date of follow-up (up to 5 years)
Quality of life
Quality of life as measured by EORTC Quality of Life Questionnaire Core 30 Items periodically
Time frame: Before and 12 weeks after completion of treatment
Toxicity
Toxicity as measured by NCI CTC periodically. The proportion of patients who experience a toxicity of grade 3 or 4 will be compared between the two arms of the trial.
Time frame: During treatment and follow-up
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Derbyshire Royal Infirmary
Derby, England, United Kingdom
Princess Alexandra Hospital
Essex, England, United Kingdom
Gloucestershire Royal Hospital
Gloucester, England, United Kingdom
Princess Royal Hospital at Hull and East Yorkshire NHS Trust
Hull, England, United Kingdom
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, United Kingdom
...and 15 more locations