Prophylactic combined chemotherapy for patients with cholangiocarcinoma after curative intent of carcinoma resection and muscle invasive gallbladder carcinoma.

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 781

Inclusion Criteria

Eligibility criteria for enrolment phase
1.Suspicion of or histologically/cytologically confirmed adenocarcinoma of biliary tract (intrahepatic, hilar or extrahepatic cholangiocarcinoma or muscle invasive gallbladder carcinoma) scheduled for radical surgical therapy
2.Written informed consent
3.No prior chemotherapy for biliary tract cancer
4.No previous malignancy within 3 years or concomitant malignancy, except: those with a 5 year overall survival rate of more than 90%, e.g. non-melanomatous skin cancer or adequately treated in situ cervical cancer
5.No severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction in the last 3 months, significant arrhythmia)
6.Absence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent
7.No serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial
8.Fertile women (< 1 year after last menstruation) and procreative men willing and able to use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile)
9.No pregnancy or lactation

Eligibility criteria for treatment phase (before randomization)

All enrolled patients will postoperatively be assessed for eligibility for the treatment phase. Additionally patients not previously enrolled into the trial for whatever reason (e.g. incidental finding during surgery) will be evaluated for eligibility.

1.Histologically confirmed non metastatic adenocarcinoma of biliary tract (intrahepatic, hilar or extrahepatic cholangiocarcinoma or muscle invasive gallbladder carcinoma) after radical surgical therapy with macroscopically complete resection (mixed tumor entities (HCC/CCA) are excluded) (according to appendix H)
2.Macroscopically complete resection (R0/1) within 6 (-16) weeks before scheduled start of chemotherapy
3.ECOG 0-1
4.Age =18 years
5.Adequate hematologic function: ANC ?1.5 x 109/L, platelets ?100 x109/L, hemoglobin ?9 g/dl or ?5.59 mmol/L
6.Adequate liver function as measured by serum transaminases (AST and ALT) £5 x ULN and bilirubin £3 x ULN
7.Adequate renal function, i.e. serum creatinine £1.5 x ULN, glomerular filtration rate = 50 ml/min (determination of GFR according to local institutional standards, e.g. MDRD, (Appendix E))
8.No active uncontrolled infection, except chronic viral hepatitis under antiviral therapy
9.No concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to randomization
10.Negative serum pregnancy test within 7 days of starting study treatment in pre-menopausal women and women <1 year after the onset of menopause (Note: a negative test has to be reconfirmed by a urine test, should the 7-day window be exceeded)

Criteria for initial study enrolment
11.Written informed consent
12.No prior chemotherapy for biliary tract cancer
13.No previous malignancy within 3 years or concomitant malignancy, except: those with a 5 year overall survival rate of more than 90%, e.g. non-melanomatous skin cancer or adequately treated in situ cervical cancer
14.No severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardia

Exclusion Criteria

Eligibility criteria for enrolment phase
1.Suspicion of or histologically/cytologically confirmed adenocarcinoma of biliary tract (intrahepatic, hilar or extrahepatic cholangiocarcinoma or muscle invasive gallbladder carcinoma) scheduled for radical surgical therapy
2.Written informed consent
3.No prior chemotherapy for biliary tract cancer
4.No previous malignancy within 3 years or concomitant malignancy, except: those with a 5 year overall survival rate of more than 90%, e.g. non-melanomatous skin cancer or adequately treated in situ cervical cancer
5.No severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction in the last 3 months, significant arrhythmia)
6.Absence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent
7.No serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial
8.Fertile women (< 1 year after last menstruation) and procreative men willing and able to use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile)
9.No pregnancy or lactation

Eligibility criteria for treatment phase (before randomization)

All enrolled patients will postoperatively be assessed for eligibility for the treatment phase. Additionally patients not previously enrolled into the trial for whatever reason (e.g. incidental finding during surgery) will be evaluated for eligibility.

1.Histologically confirmed non metastatic adenocarcinoma of biliary tract (intrahepatic, hilar or extrahepatic cholangiocarcinoma or muscle invasive gallbladder carcinoma) after radical surgical therapy with macroscopically complete resection (mixed tumor entities (HCC/CCA) are excluded) (according to appendix H)
2.Macroscopically complete resection (R0/1) within 6 (-16) weeks before scheduled start of chemotherapy
3.ECOG 0-1
4.Age =18 years
5.Adequate hematologic function: ANC ?1.5 x 109/L, platelets ?100 x109/L, hemoglobin ?9 g/dl or ?5.59 mmol/L
6.Adequate liver function as measured by serum transaminases (AST and ALT) £5 x ULN and bilirubin £3 x ULN
7.Adequate renal function, i.e. serum creatinine £1.5 x ULN, glomerular filtration rate = 50 ml/min (determination of GFR according to local institutional standards, e.g. MDRD, (Appendix E))
8.No active uncontrolled infection, except chronic viral hepatitis under antiviral therapy
9.No concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to randomization
10.Negative serum pregnancy test within 7 days of starting study treatment in pre-menopausal women and women <1 year after the onset of menopause (Note: a negative test has to be reconfirmed by a urine test, should the 7-day window be exceeded)

Criteria for initial study enrolment
11.Written informed consent
12.No prior chemotherapy for biliary tract cancer
13.No previous malignancy within 3 years or concomitant malignancy, except: those with a 5 year overall survival rate of more than 90%, e.g. non-melanomatous skin cancer or adequately treated in situ cervical cancer
14.No severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardia

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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