Cholangiocarcinoma perihilar
Conditions
Interventions
SBRT will be delivered in 15 fractions of 4 to 4.5Gy after 8 cycles of
chemotherapy. In case of toxicity causing premature termination of systemic
treatment, the patient can still proceed to SBRT.
Sponsors
Erasmus MC, Universitair Medisch Centrum Rotterdam
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: The initial translational part of the study will be performed in patients with unresectable pCCA eligible for gemcitabine-based chemotherapy (*). After chemotherapy, the patients will proceed to SBRT if they are still eligible based on the following inclusion and exclusion criteria (see below). It may happen that patients do not give consent for the translational part of the study, but they may wish to participate in the SBRT part of the trial and vice versa. Inclusion criteria translational part of the study: In order to be eligible to participate in the translational part of the study, a subject must be discussed in a liver tumor board, should be eligible for gemcitabine-based chemotherapy (and immunotherapy, if applicable), and should meet all of the following criteria pre-chemotherapy: - pCCA according to the criteria of the Mayo Clinic, Rochester (22): o Positive or strongly suspicious intraluminal brush cytology or biopsy or, o A radiographic malignant appearing stricture plus either: * CA 19-9>100 U/ml in the absence of acute bacterial cholangitis, or * polysomy on fluorescence in situ hybridization (FISH), or * a well-defined mass on cross sectional imaging - One tumor mass - Unresectable tumor or patient deemed unfit for surgery - T1-T4 (AJCC staging 8th edition), N0-N2-M0 (AJCC staging 8th edition), radiologically or pathologically suspect o N1 is defined as one to three affected lymph nodes typically involving the hilar, cystic duct, common bile duct, hepatic artery, posterior pancreatoduodenal, and portal vein lymph nodes. N2 is defined as four or more affected lymph nodes from the sites described for N1. o Endoscopic ultrasound (EUS) is leading in identifying pathological lymph nodes compared to CT. - In case of (underlying) liver cirrhosis: Child-Pugh A - Age >= 18 years - ECOG performance status 0-1 - Written informed consent for the translational part of the study Inclusion criteria SBRT part of the study: Additionally, to the criteria mentioned above, patients should meet the following criteria to be eligible for the treatment with SBRT: - Measurable disease to be selected as a target on a computed tomography (CT) or magnetic resonance imaging (MRI) scan, according to RECIST 1.1 criteria - Finished gemcitabine-based chemotherapy treatment, preferably 8 cycles. If less cycles are given, patients are still eligible for this study - Bilirubin = 50x10E9/ l, Leukocytes > 1.5x10E9/l, Hemoglobin (Hb) > 6 mmol/l - Willing and able to comply to the follow-up schedule - Able to start SBRT within 12 weeks after completion of chemotherapy and immuno-therapy (if applicable) - Written informed consent for the SBRT part of the study (*) Gemcitabine-based chemotherapy will most frequently include a combination of gemcitabine and cisplatin for this patient population. However, when deemed necessary by a medical oncologist, variations of this chemotherapy regimen regarding the cisplatin may be applied. Such variations in chemotherapy regimens will be allowed in this study. Gemcitabine-based chemotherapy will be administered according to local practice. (**) This corresponds to the threshold beyond which gemcita
Exclusion criteria
Exclusion criteria: Exclusion criteria translational part of the study - Prior surgery or transplantation of the liver - Tumor extension in stomach, colon, duodenum, pancreas or abdominal wall - Ascites - Prior radiotherapy to the liver - Current pregnancy - Affected lymph nodes outside the regions described in the inclusion criteria (D4) Exclusion criteria SBRT part of the study: Progression (local or distant) during or after chemotherapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The main endpoint with regards to the radiotherapy is local tumor control. With regards to the translational part of the study the aim is to explore the value of immunodynamics in peripheral blood for predicting progression-free survival in patients undergoing chemotherapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Toxicity, biliary stent-related events (SRE) (*), progression-free survival, overall survival, quality of life. (*) The definition of SRE in this study is based on the definition used in the study by Lamarca et al. [1], and includes the following: *A SRE is defined as any one or more of the following: (1) any episode of jaundice which is considered significant enough for new stenting or medical treatment and is confirmed by radiological imaging to be associated with biliary dilatation; (2) any episode of infection which is clinically in keeping with cholangitis (bile duct infection) requiring antibiotic therapy; (3) bacteraemia with isolation in blood cultures of bacteria suspected to have originated in the biliary tract; and (4) any episode of cholecystitis or gallbladder perforation. The following will not be considered SREs: (1) jaundice related to high tumour burden liver disease with no significant change in biliary dilatation compared with previous imaging; (2) episodes of neutropenic or non-neutropenic fever with no identified biliary focus; and (3) patients with non-clinically significant biliary occlusion or biliary dilatation (i.e., radiological evidence only with no jaundice, increasing bilirubin, increasing liver function tests (LFTs), fever or evidence of infection) who require no action (no new stenting or no new antibiotic therapy).* Reference: [1]: https://doi.org/10.3748/wjg.v22.i26.6065 | — |
Countries
Netherlands
Outcome results
None listed