Prophylactic combined chemotherapy for patients with cholangiocarcinoma after curative intent of carcinoma resection and muscle invasive gallbladder carcinoma.
- Conditions
- Cholangiocarcinoma and gallbladder carcinomaMedDRA version: 20.0Level: LLTClassification code 10017620Term: Gallbladder carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10008593Term: CholangiocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-005078-70-AT
- Lead Sponsor
- niversity Medical Center Hamburg-Eppendorf
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 440
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: 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
Assessments enrolment phase (for details refer to section 5.3)Preoperatively
• Obtaining signed written informed consent
• Medical and medication history, performance status (ECOG)
• Demographics
• Laboratory tests: hematology and chemistry panel, tumor markers
• Acquisition of blood for translational research
• Quality of life assessments
Intraoperatively
• Acquisition of tissue for translational research
Postoperatively
• Acquisition of blood for translational research (during second postoperative week)
• Evaluation of feasibility for treatment phase
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 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)
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 10^9/L, platelets = 100 x10^9/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 = 60 mL/min
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 bilia
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: 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
Assessments enrolment phase (for details refer to section 5.3)Preoperatively
• Obtaining signed written informed consent
• Medical and medication history, performance status (ECOG)
• Demographics
• Laboratory tests: hematology and chemistry panel, tumor markers
• Acquisition of blood for translational research
• Quality of life assessments
Intraoperatively
• Acquisition of tissue for translational research
Postoperatively
• Acquisition of blood for translational research (during second postoperative week)
• Evaluation of feasibility for treatment phase
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 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)
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 10^9/L, platelets = 100 x10^9/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 = 60 mL/min (MDRD)
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 fo
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this study is to evaluate the efficacy of gemcitabine and cisplatin compared with observation treatment in patients with BTC after complete resection in terms of DFS.<br>;Secondary Objective: Secondary objectives are safety and tolerability of the treatment as well as OS, quality of life, function of biliodigestive anastomoses, and evaluation of the quantity and quality of information patients have gained after the informed consent as well as of the involvement of patients in the decision-making process (shared decision making).;Primary end point(s): Disease free survival (DFS);Timepoint(s) of evaluation of this end point: Every three month up to 24 month
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Disease free survival rate at 24 months (DFSR@24)<br>• Overall survival (OS)<br>• Safety and tolerability of adjuvant chemotherapy<br>• Quality of life (QoL)<br>• Function of biliodigestive anastomosis (in terms of surgical revision, requirement for PTCD)<br>• Rate and severity of biliary tract infections<br>• Patterns of disease recurrence<br>• Locoregional control <br>;Timepoint(s) of evaluation of this end point: Every three month for two years after randomization followed by 6 monthly for 3 years