The aim of the study is to demonstrate that HAIP chemotherapy is an effective treatment for unresectable intrahepatic cholangiocarcinomas.
ID
Source
Brief title
Condition
- Hepatobiliary neoplasms malignant and unspecified
- Hepatobiliary therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of this study is to evaluate efficacy, expressed by OS,
of HAIP chemotherapy and concurrent systemic chemotherapy in patient with
unresectable ICC in the Netherlands
Secondary outcome
Secondary objectives include postoperative complications, chemotherapy related
adverse events, 2-, 3- and 5-years OS, progression free survival (PFS),
response rate, conversion to resection rate, quality of life, and
cost-effectiveness. The accuracy of CT angiography to detect extrahepatic
perfusion will be measured. Next, we aim to identify predictive biomarkers for
the efficacy of HAIP chemotherapy.
In 5 patients at Erasmus MC, we aim to perform a PSMA PET-CT/MRI to measure
PSMA expression in ICC tumours.
Background summary
Intrahepatic cholangiocarcinoma (ICC) is the second most prevalent primary
liver cancer after hepatocellular carcinoma, and is increasing in incidence.
ICC makes up about 10% of all cholangiocarcinomas. It is an aggressive
malignancy that arises from the epithelium of bile ducts. ICC is most prevalent
in East Asian, with incidences ranging from 10 to 71 per 100.000 persons.(2, 3)
A correlation with diseases causing biliary inflammation, such as primary
sclerosing cholangitis has been noted. The incidence of ICC in the western
world countries is approximately 1 per 100.000.
Complete resection remains the only curative option, which is only feasible in
the minority of patients (15%). Resection results in a median survival of less
than 3 years. Most of ICCs, however, present at an advanced unresectable stage
with limited treatment options due to the usually clinically silent
progression, and consequently its late manifestation. Overall survival (OS) of
patient with unresectable ICCs is reported to be 5 months without treatment and
approximately 1 year with systemic chemotherapy. The five year survival rate is
approximately 5%. Currently used treatment regimens consist of gemcitabine and
cisplatin, which offers minimal OS benefit over gemcitabine monotherapy (11.7
versus 8.1 months, respectively). Another trial found similar results of 11.2
and 7.7 respectively (not significant, however, due to lack of power). Previous
results are similar to other gemcitabine-based regimes, such as gemcitabine and
oxaliplatin. A post-hoc analysis of 34 patients with unresectable liver only
ICC, treated with gemcitabine and cisplatin, showed 3-years OS of 0%. More
effective therapies are needed to improve survival.
Study objective
The aim of the study is to demonstrate that HAIP chemotherapy is an effective
treatment for unresectable intrahepatic cholangiocarcinomas.
Study design
Patients with an unresectable intrahepatic cholangiocarcinoma are included in
the study, provided they give oral and written consent. In addition to the
regular systemic chemotherapy, the study subjects will receive an operation for
the placement of the infusion pump and will subsequenty undergo 6 consecutive
cycles (4 weeks per cycle) of chemotherapy via the infusion pump.
Intervention
Operation for placement of the infusion pump. 2 to 4 weeks later, patients with
6 consecutive cycles (4 weeks per cycle) of chemotherapy via the pump.
Study burden and risks
Patients will be hospitalised for 4 days to surgically place the pump and to
provide the technetium99-labeled macoaggreted albumin scan. After the
operation, 6 cycles of chemotherapy are administered subcutaneously into pump.
This regimen will be followe in conjunction to the regular chemotherapy. For
these 6 cycles 12 outpatient appointments are necessary, which are combined
with the regular appointments for systemic chemotherapy.
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
• Age >= 18 years.
• ECOG performance status 0 or 1
• Histologically confirmed diagnosis of intrahepatic cholangiocarcinoma (ICC).
• Unresectable ICC confined to the liver (<70% of the liver involved) with or
without limited regional lymph node disease (portal) at initial presentation,
as confirmed by HPB surgeons. Regional lymph nodes will be allowed, provided it
is potentially amenable to resection.
Unresectability confirmed:
o Radiologically
o Or during surgical exploration in patients initially considered candidates
for resection
• Patient is able to undergo a laparotomy or minimal-invasive surgery for pump
placement.
• Positioning of a catheter for HAIP chemotherapy is technically feasible (see
chapter 5) based on a CT with excellent arterial phase. The default site for
the catheter insertion is the gastroduodenal artery (GDA). Accessory or
aberrant hepatic arteries are no contraindication for catheter placement.
• Adequate bone marrow, liver and renal function as assessed by the following
laboratory requirements to be conducted within 30 days prior to inclusion:
o Absolute neutrophil count (ANC) >= 1.5 x 109/L
o White blood cell count (WBC) >= 2.5 x 109/L
o Platelets >= 100 x 109/L
o Glomerular filtration rate (GFR) >= 50 ml/min
o Haemoglobin (HB) >= 5.5 mmol/L
o Total bilirubin <= 25 µmol/L
Exclusion criteria
•Presence of extrahepatic disease at the time of first presentation. Patients
with limited (portal) lymph node disease, patients with small (<= 1 cm)
extrahepatic lesions that are too small to characterize are eligible.
• Second primary malignancy, except for adequately treated non-melanoma skin
cancer, or other malignancy treated at least 3 years previously without
evidence of recurrence or with a life expectancy longer than 5 years.
• Known DPYD deficiency. Patients with intermediate DPYD metabolism ( DPD
activity score: 1.5) are eligible and a 50% reduced starting dose of
floxuridine will be administered by discretion of the medical oncologist.
• Prior hepatic radiation, ablation, or resection for cholangiocarcinoma.
• Life expectancy of less than 12 weeks.
• Clinical evidence of portal hypertension (ascites, gastroesophageal varices,
or portal vein thrombosis). Surgically related ascites is allowed.
• (Partial) portal vein thrombosis.
• Pregnant or lactating women.
• History of psychiatric disability judged by the investigator to be clinically
significant, precluding informed consent or interfering with compliance for
HAIP chemotherapy.
• Serious concomitant systemic disorders that would compromise the safety of
the patient or his/her ability to complete the study, at the discretion of the
investigator.
• Organ allografts requiring immunosuppressive therapy.
• Serious, non-healing wound, ulcer, or bone fracture.
• Chronic treatment with corticosteroids (dose of >= 10 mg/day
methylprednisolone equivalent excluding inhaled steroids).
• Serious infections (uncontrolled or requiring treatment).
• Participation in another interventional study for ICC with survival as
outcome.
• Participation in another prospective study with an interventional medical
product.
• Any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up
schedule; those conditions should be discussed with the patient before
registration in the trial.
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
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-004013-41-NL |
| CCMO | NL70452.078.19 |
| OMON | NL-OMON23810 |