The aim of this study is to find out whether the addition of HAIP chemotherapy with floxuridin in patients with operable iCCA is effective, i.e. the time to recurrence is longer than with standard care.
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 main trial endpoint is the rate of recurrence of iCCA in the liver after
two years.
Secondary outcome
Secondary endpoints will be: complications after the surgery to remove the
iCCA, complications from the chemotherapy (FUDR), the rate of recurrence of the
cancer in general, quality of life, cost-effectiveness of HAIP chemotherapy,
and biomarkers in the blood to predict effectivity of HAIP chemotherapy.
Background summary
Intrahepatic cholangiocarcinoma (iCCA), a type of liver cancer in the bile
ducts of the liver, has a 30% survival rate after resection, and about
two-thirds of patients face a recurrence, often (approx. 80%) in the liver.
Hepatic arterial infusion pump (HAIP) chemotherapy, delivering a drug called
floxuridine (FUDR) directly to the liver, has shown a 60% success rate in
controlling unresectable iCCA . This method aims to reduce liver recurrence by
targeting occult micrometastases left after resection. FUDR, administered this
way, reaches very high concentrations in the tumour without causing widespread
side effects. The hypothesis of this trial is that the hepatic recurrence free
survival time will increase in patient treated with HAIP chemotherapy.
Study objective
The aim of this study is to find out whether the addition of HAIP chemotherapy
with floxuridin in patients with operable iCCA is effective, i.e. the time to
recurrence is longer than with standard care.
Study design
A prospective multicentre single arm phase II trial, where patients receive
surgery and as an addition HAIP chemotherapy.
Intervention
During the resection of iCCA, there will be a subcutaneous chemopump implanted.
By means of this chemopump, a chemotherapeutical agent called Floxuridin will
be administered to the liver tumour through a small catheter. A maximum of 4
cycles of floxuridin will be given to a trial subject (=16 weeks of treatment).
Study burden and risks
The intervention (HAIP chemotherapy) is an addition to the standard care.
Burden related to surgery:
During the liver resection a subcutaneous pump will be implanted. Surgical
complications related to HAIP pump placement are uncommon (+/-10%), and include
hepatic artery thrombosis, hepatic artery dissection, and bleeding at the site
of catheter insertion, catheter dislocation, pump dysfunction, pump migration
(flipping), pump pocket infection, pump pocket seroma, and pump pocket hematoma.
Burden related to imaging:
Prior to the first administration of HAIP chemotherapy, a nuclear scan is
performed to confirm adequate blood flow in the liver and rule out leakage of
chemotherapy outside of the liver. The radiation dose of the scan is low.
CT-scans of the chest and abdomen during treatment and follow-up are performed
every 6 months after operation in the first and second year and every year
thereafter until the end of follow-up after 5 years.
Burden related to HAIP chemotherapy administration:
Two additional hospital visits per cycle are required for HAIP chemotherapy. A
maximum number of 4 cycles will be administered with a maximum of 8 additional
visits. At each visit a blood sample of 50 mL will be taken to evaluate
toxicity. HAIP chemotherapy toxicity is mainly biliary sclerosis (5.5%), which
is largely avoided by monitoring of liver tests and dosages adjustments. In
case of increased liver function test that may reflect impending biliary
obstruction, high dose of dexamethasone is administered through the pump.
Systemic side effects with HAIP chemotherapy of floxuridin are rare (<1%).
Burden related to Quality of Life questionnaires:
All patients will be asked to complete Quality of Life (QoL) questionnaires
questionnaire at five time points (baseline, 3, 6, 9 and 12 months (+/- 30
days)) during the first year of this trial. After 1 year of follow up the
questionnaires will be taken annually.
Burden related to biomarker assessments:
Five blood samples are scheduled with a total volume of 150 ml. The time points
of the biomarker assessments are:
• The day of surgery before incision
• During surgery directly drawn from the hepatic vein
• At the start of HAIP chemotherapy
• After the last cycle of HAIP chemotherapy
• At one year after surgery or once recurrence of iCCA occurs
Dr. Molewaterplein 40
Rotterdam 3015GD
NL
Dr. Molewaterplein 40
Rotterdam 3015GD
NL
Listed location countries
Age
Inclusion criteria
- Age >= 18 years.
- ECOG performance status 0 or 1
- Diagnosis of resectable iCCA on imaging. No histological confirmation is
needed before surgery, according to standard of care.
- Patient is able to undergo a laparotomy.
- Positioning of a catheter for HAIP chemotherapy is technically feasible based
on a CT-scan with early arterial phase with 1mm cuts. The default site for the
catheter insertion is the 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:
+ Absolute neutrophil count (ANC) >= 1.5 x 109/L
+ White blood cell count (WBC) >= 2.5 x 109/L
+ Platelets >= 100 x 109/L
+ Glomerular filtration rate (GFR) >= 30 ml/min
+ Haemoglobin (Hb) >= 5.5 mmol/L
+ Total bilirubin <= 25 µmol/L
- Written informed consent must be given according to ICH/good clinical
practice (GCP), and national/local regulations.
Exclusion criteria
- Presence of extrahepatic disease at the time of first presentation. Patients
with locoregional lymph node disease or with small (<= 1 cm) extrahepatic
lesions that are too small to characterise 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 homozygous dihydropyrimidine dehydrogenase (DPYD) deficiency.
- Prior hepatic radiation, ablation, or resection for iCCA.
- Clinical evidence of portal hypertension (ascites, gastroesophageal varices,
or portal vein thrombosis). Some postoperative ascites is allowed.
- (Partial) portal vein thrombosis in future liver remnant.
- 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.
- 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 iCCA 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
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL86208.078.24 |