To evaluate the effect of combined PVE/HVE compared to PVE alone on resectability and overall survival in patients with primary liver cancers.
ID
Source
Brief title
Condition
- Hepatobiliary neoplasms malignant and unspecified
- Hepatobiliary neoplasms malignant and unspecified
- Hepatobiliary therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
A split primary endpoint will be evaluated: resectability and overall survival.
* The FLR is considered sufficient for resection 3 weeks after embolisation.
Definition resectable: Patients are deemed resectable if the FLR is >=30% in
normally functioning livers, >=40% in livers with potentially impaired function
(e.g. resulting from prior systemic therapy or bile duct colonization /
transpapillary biliary drainage), or >=50% in livers with severely impaired
function resulting from liver cirrhosis (max. Child Pugh A5) OR for any FLR
volume, function on hepatobiliary scintigraphy is > 2.67 %/min/m2
* 5-year overall survival
Secondary outcome
Additional outcomes will be assessed in order to compare PVE/HVE to PVE
embolisation. These endpoints entail several read-outs regarding liver growth,
complications and 90-day survival after embolization and resection, clinical
resection rates, composites of resectability and 90-day survival, QoL of the
patient, costs, salvage procedures in case of insufficient FLR growth after
embolization, recurrence and oncological interventions during follow-up. A
detailed overview of all secondary endpoints is given in Section 4.
Background summary
Primary liver cancer (PLC) is the third most common cause of cancer death
worldwide. Surgical resection is the mainstay for a curative approach as
contemporary chemotherapy and immune-based therapies only lead to a median
survival of 10-14 months. A complete surgical resection increases the median
survival to 42 months (range 32-52 months). However, PLC is mainly diagnosed at
an advanced stage and >70% of PLC patients are ineligible for an immediate
surgical approach. There are different reasons that make a patient ineligible
for surgery, one important reason is the risk of liver failure after the
surgery due to a small remnant liver.
This study aims to improve the oncological, radiological and surgical strategy
to allow more patients to undergo liver resection safely, to improve quality of
life and to extend overall survival at acceptable costs.
Adequate function of the future liver remnant (FLR) is a prerequisite for
surgical resectability. This is necessary in order to avoid liver failure after
surgery, a major cause of morbidity (38%) and mortality (27%). To mitigate this
risk, regenerative strategies based on preoperative calculation of the FLR
volume and function are essential. Patients with technically resectable disease
but predicted insufficient FLR volume or function are referred to as primarily
unresectable or potentially resectable (PU/PR). These patients can undergo
strategies that capitalize on the regenerative capacity of the liver which aim
to preoperatively increase the FLR volume and function in order to allow
surgery. Many of the patients that are primarily unresectable due to an
insufficient FLR can become ultimately and safely resectable after the
induction of adequate FLR-hypertrophy by the current standard, portal vein
embolisation (PVE). However, 25% of patients do not show sufficient FLR growth
after PVE and are unable to safely undergo resection. A new approach has been
developed to improve this. Combined portal and hepatic vein embolisation
(PVE/HVE) has great promise in terms of increasing FLR growth, resection rate
(RR), safety and potentially, overall survival. Establishing PVE/HVE as the new
standard could result in increased survival and a better quality of life (QoL)
for patients.
Study objective
To evaluate the effect of combined PVE/HVE compared to PVE alone on
resectability and overall survival in patients with primary liver cancers.
Study design
An international multicentre randomised controlled trial (see appendix A for an
overview of all participating centres) in which patients will be randomised
(1:1) in centre and cancer type-stratified blocks into two arms: combined
PVE/HVE and PVE alone. In total 358 patients will be included (n=179 patients
per arm).
Intervention
The study interventions consist of a combined Portal Vein and Hepatic Vein
Embolisation (PVE/HVE) in the intervention group and PVE only in the control
group. After the intervention, patients will have follow-up visits with
computed tomography (CT) liver volumetry scans at 1 week, 3 weeks and 6 weeks
after embolisation. If a sufficient FLR volume is already reached after 1 week
or 3 weeks, the subsequent visits are no longer necessary.
Study burden and risks
There are no trial-specific risks expected for the group receiving PVE/HVE
treatment. Based on a previous safety study (DRAGON 1) and retrospective
analyses, no increased risk of adverse outcomes is expected between groups.
Hospital visits, admissions and number of follow-up appointments do not differ
between the intervention group and the standard care. On average, the procedure
of the intervention group will be one hour longer. Patients will be asked to
fill out questionnaires at six time points during the first year after
inclusion, twice in the second year and third year, and once a year in year 4
and 5. Overall, the additional burden of patients receiving the planned
intervention compared to standard treatment is limited.
*
Universiteitssingel 50
Maastricht 6229 ER
NL
Universiteitssingel 50
Maastricht 6229 ER
NL
Listed location countries
Age
Inclusion criteria
- PLC diagnosis, specifically intrahepatic cholangiocarcinoma (iCCC), perihilar
cholangiocarcinoma (pCCC), and hepatocellulair carcinoma (HCC);
- Requiring PVE due to an FLR volume is <30% in normally functioning livers,
<40% in livers with potentially impaired function e.g. resulting from prior
systemic therapy induction or bile duct colonization / transpapillary biliary
drainage, or <50% in livers with severely impaired function resulting from
liver cirrhosis (max. Child Pugh A5) OR function on hepatobiliary scintigraphy
(HEBIS) is < 2.67 %/min/m2;
- Age >= 18 years;
- Able to understand the trial and provide informed consent.
Exclusion criteria
- Liver cirrhosis with a Child-Pugh score of B or C;
- Presence of portal hypertension;
- Presence of cholangitis;
- Pregnant women;
- Premenopausal females not able/willing to commit to contraception
(specifically long-acting reversible contraception or hormonal contraception);
- Patients unresectable due to prohibitive comorbidities (decision made by
local multidisciplinary team);
- Patients with hepatic malignancies other than iCCC, pCCC or HCC;
- PVE/HVE anatomically not feasible;
- Any patient with non-resectable or non-ablatable extrahepatic metastatic
disease.
- Unable to understand the study information, study instructions and give
informed consent.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL87590.068.24 |