This study is primarily set up to investigate the safety and feasibility of IRE for the treatment of unresectable, locally advanced or nodal metastasized PHC. The efficacy of IRE will also be studied.
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is safety, defined as the total number of clinically
relevant complications (Common Terminology Criteria for Adverse Events [CTCAE],
score of 3 or higher) within 90 days post-IRE.
Secondary outcome
Secondary outcomes are the success rate of completing IRE, intra-procedural
complications related to IRE, duration of hospital stay, quality of life,
impact of IRE on post-procedural CT imaging and blood biomarker response, time
between IRE and start of palliative chemotherapy, metal stent patency,
progression-free and overall survival.
Background summary
The majority of patients with perihilar cholangiocarcinoma (PHC) have locally
advanced disease or lymph node metastases upon presentation or exploratory
laparotomy, which makes resection not amenable. As the prognosis of patients
with locally advanced PHC (LAPHC) or PHC with lymph node metastases in the
palliative setting is significantly better compared to patients with organ
metastases, ablative therapies may be beneficial.
Unfortunately, current ablative techniques are limited. Photodynamic therapy
causes skin phototoxicity and thermal ablative methods, such as stereotactic
body radiation therapy and radiofrequency ablation, are affected by a
heat/cold-sink effect when tumors are located close to vascular structures,
such as the liver hilum. These limitations may be overcome by irreversible
electroporation (IRE), which is a relatively new, non-thermal ablative method
that is currently being studied in several other soft tissue tumors, such as
pancreatic adenocarcinoma.
Study objective
This study is primarily set up to investigate the safety and feasibility of IRE
for the treatment of unresectable, locally advanced or nodal metastasized PHC.
The efficacy of IRE will also be studied.
Study design
A multicenter phase I/II safety study.
Intervention
Computed tomography-guided percutaneous IRE (N=11)
Open IRE (N=1), inclusion in this group closed
Study burden and risks
The risks associated with participation in this study are the adverse events of
the procedure (i.e. cardiac arrhythmias, perforation, bile leakage, portal vein
thrombosis, bleeding, intra-abdominal abscess, infections). The risk of this
study is classified as 'high'. A potential benefit can be that patients will
have an improvement of several months in progression-free and potentially
overall survival. The second potential benefit can be that biliary stents will
be patent for a longer period of time.
The potential risks associated with NanoKnife treatment are considered
acceptable in this selected group of unresectable patients. Previous analysis
of patients with unresectable PHC at the AMC has shown a median overall
survival of 14 and 16 months for lymph node metastasized and locally advanced
disease, respectively. Some of these patients had long-term survival of more
than 36 months. Compared to a median overall survival of 3 and 5 months for
patients who receive palliative chemotherapy for liver- and extrahepatic
metastases, respectively, patients with earlier stages seem to have
biologically more favorable tumors with indolent growth. When these patients
are no candidates for liver transplantation, they may potentially benefit from
local ablative therapies in combination with palliative chemotherapy.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
* Age 18 years or older
* Capable of providing written and oral informed consent
* WHO *2
* Meets criteria for advanced PHC
o Local recurrent disease localized on the distal bile duct remnant,
hepatico-jejunostomy or in the liver hilum without N2 lymph nodes or distant
metastases .
* Diagnosis of PHC or lymph node metastases must be confirmed with endoscopic
brush, percutaneous- or laparoscopic biopsy, whichever is suitable, o Vascular
or lymph node (N2) involvement on imaging or during staging laparoscopy
Diagnosis of PHC or lymph node metastases beyond N2 stations
must be confirmed with endoscopic brush,
percutaneous- or laparoscopic biopsy, whichever is suitable
o Vascular or lymph node (N2) involvement during exploratory laparotomy
Must be confirmed with intra-operative frozen section
Exclusion criteria
* Resectable PHC upon exploratory laparotomy
* Locally advanced PHC eligible for liver transplantation (Appendix 3)
* PHC with > 5 cm extension along the common hepatic duct or common bile duct
* Metastases to peritoneum, liver or other organs confirmed by percutaneous
biopsy, staging laparoscopy or intraoperative frozen section
* Lymph node metastases beyond N2 stations (e.g. inguinal, mediastinal)
* History of cardiac arrhythmia*s (any of the following)
o Sinus tachycardia (BPM>100)
o Sick sinus syndrome
o Sinoatrial exit block
o AV block
o Sinus node reentry
o Presence of a pacemaker or defibrillator
* Recent history of myocardial infarction (<6 maanden)
* Uncontrolled hypertension (blood pressure must be *160/95 mmHg at the time of
screening on a stable antihypertensive regimen
* Uncontrolled infections (> grade 2 NCI-CTC, version 3.0)
* Epilepsy
* Both narrowing (sclerosis) of the portal vein and a reduced diameter of
either the common hepatic artery, celiac trunk or superior mesenteric artery of
>50%
* Any condition that is unstable or that could jeopardize the safety of the
subject and their compliance in the study
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL56231.018.15 |
| OMON | NL-OMON25184 |