proximal bile duct cancer
Conditions
Interventions
Product Name: Gemcitabine
Pharmaceutical Form: Powder for infusion*
INN or Proposed INN: GEMCITABINE
CAS Number: 95058-81-4
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: up t
Sponsors
Universitätsmedizin Charite
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Listing for liver transplantation • diagnosis of hilar cholangiocarcinoma with or without primary sclerosing cholangitis (PSC): i.e. histological diagnosis of cholangiocarcinoma (obtained via ERC) or dominant stenosis plus cytological diagnosis of severe dysplasia or two subsequent cytological results of severe dysplasia or carcinoma whereby the second has been obtained after 2 weeks of antibiotic treatment to exclude inflammatory changes • tumor not curatively resectable as judged by one local experienced hepatobiliary surgeon (> 50 liver resections for hilar cholangiocarcinoma) • on-line review (protective website) of defined patient data and acceptance for priority listing by an Eurotransplant expert panel consisting of two experts recruited from the Eurotransplant Liver Allocation Committee; in case of split decision addition of a third expert for definite decision on priority listing with an respective matchMELD. • obligatory staging laparotomy before priority listing (see SOP staging laparotomy) • age between 18 and 65 years • negative pregnancy test • informed consent before study specific procedures are performed (i.e. at the time of randomization for chemotherapy, all other procedures are clinical routine procedures in the management of these patients) for randomization adj. chemotherapy vs. observation: • liver transplantation within three months after listing for liver transplantation • histologically proven proximal bile duct cancer • curative resection of the tumor (R0) • in case of previously unknown hilar lymph node metastases nearby the tumor region in the final pathological report: stratification in the treatment groups • no previous photodynamic therapy, radiation, chemotherapy, brachytherapy or combinations of these procedures • CT scan of the chest not older than 8 weeks before randomization showing no detectable distant metastases • possibility to start adjuvant chemotherapy between 4 and 8 weeks (but not later than 10 weeks) after liver transplantation • sufficient bone marrow function (WBC > 3.5/nl, platelets > 80/nl, hemoglobin > 8 g/dl) • sufficient renal function (creatinin clearance = 30 ml/min) • sufficient liver function (bilirubin =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Contraindications for liver transplantation: • locally very advanced, irresectable tumor infiltrating adjacent other organs, the main trunk of the hepatic artery • a visible tumor mass on CT or MRI scan larger than 3 cm in diameter • highly elevated CA 19-9 levels (> 1000 U/ml) • tumors suspicious for gallbladder cancer • known lymph node or distant metastasis (determined mandatory by CT scan and laparoscopy, further investigations if deemed necessary, PET scan is strongly recommended) • patients undergoing multi-organ transplantation or have undergone previous solid organ or bone marrow transplantation • previous or intended photodynamic therapy, radiation, chemotherapy, brachytherapy or combinations of these procedures • previous tumor biopsy (except via ERC) systematic lymphadenectomy (except SOP defined staging laparotomy), surgical preparation at the region of the hepatoduodenal ligament (except cholecystectomy for other reasons) or previous completed or attempted surgery for hilar cholangiocarcinoma • patients with known hypersensibility for gemcitabine • pregnancy or breastfeeding • patients unwilling to consent to saving and propagation of pseudonymized medical data for study reasons • general contraindications for liver transplantation • subjects who are legally detained in an official institute • HIV infection (based on testing performed during the transplant-evaluation or within 6 months before) for randomization (adj. chemotherapy vs. observation): • patients with biliary sepsis, intrahepatic abscesses or other complications (e.g. severe liver dysfunction) contraindicating adjuvant chemotherapy • contraindications against study medication (including auxiliary substances) • pregnancy or breastfeeding • induction therapy with antibodies as primary immunosuppression after liver transplantation (rejection treatment with antibodies is not a contraindication) • therapy with mTOR-inhibitors (sirolimus, everolimus) • any clinically significant medical or surgical condition, that in the investigator`s opinion would preclude adjuvant chemotherapy • participitation in other clinical trials
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate, if adjuvant gemcitabine chemotherapy is feasible in = 85 % of patients after liver transplantation.;Secondary Objective: To obtain preleminary data on recurrence- and survival rates after liver transplantation for hilar cholangiocarcinoma using strict selection criteria and either adjuvant or no adjuvant chemotherapy.;Primary end point(s): Primary endpoints: • percentage of patients completing the 24 weeks course of adjuvant chemotherapy Secondary endpoints: • recurrence free survival at 12 months • overall survival at 3 and 5 years • complication rate (protocol defined high grade toxicities grade 3/4) • number of patients, which could not be randomized (due to perioperative complications, no detectable bile duct cancer in the explanted liver or other reasons) | — |
Countries
Germany
Outcome results
None listed