HAI-Floxuridine, or SIRT, Combined With Gemox For Patients With Intra-Hepatic Cholangiocarcinoma Not Amenable to Resection (TOMCAT)

NCT06313203 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 'TOMCAT' SMR-4066
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with intrahepatic cholangiocarcinoma (IHC) have relatively aggressive tumors, and the prognosis for most of these patients is dismal. Surgery is the only option that can offer potential cure, but only an estimated 20-25 % are amenable to resection. Down-staging conventional chemotherapy has a relatively low response rate (\< 50 %). Patients will be included into the respective treatment arms based on their tumour characteristics and disease stage, but also based on their ability/preferences, as HAI-FUDR/DEX requires going to Oslo every fortnight for the duration of the treatment and SIRT has some limitations regarding tumour distribution. Data from the MSKCC has suggested a clinically relevant benefit from adding intrahepatic chemotherapy to systemic therapy. HAI-FUDR/DEX is not approved in Norway and can only be evaluated in a protocolized trial. Given the risk of distant disease progression with IHC, the addition of conventional systemic chemotherapy makes good clinical sense, and data from MSKCC supports this approach. SIRT is another modality also applied trans-arterially and directly into the tumour. This treatment is approved in Norway and available in Bergen and in Oslo. It is far less cumbersome to deliver and maintain than HAI-FUDR/DEX. The efficacy and safety of the two treatment groups, HAI-FUDR/DEX and SIRT, will be compared in a parallel cohort (non-randomized) design

Conditions

Chemotherapy Effect; Intrahepatic Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS) at 3 years

  The study will assess whether the combination of systemic chemotherapy (current standard) with either SIRT or HAI-FUDR/DEX for patients not amendable to upfront resection may increase the possibility for later resection nad/or prolong survival.

  3 years

Secondary Outcomes (6)

• Tumor response

  from date of inclusion and every 8 weeks (after each cycle of chemotherapy), until death or tumor progression, up to 156 weeks (3 years)

• Quality of Life by using EORTC QLQ-C30

  From date of inclusion, and every 8 weeks until death or other illness-related incident. Up to 156 weeks (3 years)

• Quality of Life by using EQ-5D-5L

  From date of inclusion, and every 8 weeks until death or other illness-related incident. Up to 156 weeks (3 years)

• Assess the resection rate following downstaging

  3 years

• Assess complications, toxicity and side effects in treatment groups

  Within 30 days of surgery, then at every clinic visit (every 2 weeks) until death or other illness-related incident. Up to 156 weeks (3 years)

Study Arms (2)

Hepatic artery infusion (HAI) chemotherapy

ACTIVE COMPARATOR

Liver-directed hepatic arterial chemotherapy delivered through a surgically implanted HAI-pump has been evaluated in several small series and appears to have greater efficacy than systemic therapy alone.

Drug: Floxuridine

Selective Internal Radiation Therapy (SIRT)

ACTIVE COMPARATOR

SIRT is approved in Norway, however, usen in a limited degree. Recent research in hepatocellular carcinoma has shown the importance of personalized dosimetry to obtain high tumour radiation dose, while limiting the dose to surrounding liver tissue, yielding improved response and survival (Dosisphere study), It is likely that these findings can be applied also to cholangiocarcinoma.

Procedure: Selective Internal Radiation Therapy (SIRT)

Interventions

Selective Internal Radiation Therapy (SIRT) PROCEDURE

Radioactive Yttrium 90 (Y-90) labeled particles are injected selectively into the feeding arteries of the tumour(s). This allows a high radiation dose in the lesions while limiting systemic side effects.

Selective Internal Radiation Therapy (SIRT)

Floxuridine DRUG

A laparotomy will be performed and a catheter placed in the hepatic artery Connected to a subcutaneous pump. This pump will be percutaneously filled with Floxuridine 6 times in 2 weeks cycles, alternating with heparin-solution. The patients in this arm will also be given GemOX as systemic chemotherapy

Also known as: Hepatic Artery Infusion Chemotherapy

Hepatic artery infusion (HAI) chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Intra-hepatic cholangiocarcinoma. Diagnosis confirmed by biopsy, cytology or previous resection.
• Not amenable for upfront resection. Defined as:
• A tumour that is technically not resectable with R0 margins (i.e. where resection will not yield an FLR of sufficient size and function) without reconstruction of portal or liver vein, or artery.
• Any multifocality (more than one tumour) irrespective of distance between assumed primary and other lesions
• Recurrent tumour following resection
• Radiologically or cytology-proven malignant regional lymph nodes
• Disease confined to the liver or associated with limited, resectable porta hepatis lymph node metastases
• Radiologically measurable disease with at least one lesion \> 2 cm in greatest diameter
• Physical performance score WHO/ECOG stage 0/1
• Age \> 18 years
• Assumed ability to tolerate at least one full cycle of GemOx
• For eligibility to HAI-FUDR/DEX treatment, patients must be willing and able to go to Oslo every fortnight
• Women of childbearing age and potential must be willing to use highly effective contraception during the study and for a period after the study, as defined in this protocol. Male patients or male patients who have female partners of childbearing age and potential must be willing to use highly effective contraception during the study and for a period after the study, as defined in this protocol. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly.

You may not qualify if:

• Any non-liver malignant deposit (except for resectable, hilar lymph nodes)
• Serum bilirubin, creatinine or INR outside of normal range
• Haemoglobin \< 7 g/dL and thrombocytes \< 75 × 109/L
• Liver failure (if cirrhosis, Child-Pugh B or C)
• Clinical evidence of portal hypertension (non-surgically related ascites, gastro-oesophageal varices, portal vein thrombosis)
• History of peripheral neuropathy
• More than 70 % of liver consisting of tumour
• History of other malignancy past three years except localized/early stage cancer that has been adequately resected.
• Pregnant or lactating women
• Expected life expectancy less than three months.
• Inability to comply with study routines or follow-up procedures
• Inability to read and comprehend Norwegian
• Arterial anatomy unsuited for SIRT or HAI, respectively
• Any reason why, in the view of the investigators, the patient should not be included

Sponsors & Collaborators

• Oslo University Hospital: lead

Study Sites (1)

Oslo University Hospital

Oslo, Oslo County, 0424, Norway

RECRUITING

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

Floxuridine

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Deoxyuridine; Uridine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Head of Department of HPB-surgery at Oslo University Hospital, MD, PHD,

Study Record Dates

• First Submitted: February 27, 2024
• First Posted: March 15, 2024
• Study Start: February 13, 2024
• Primary Completion (Estimated): January 1, 2031
• Study Completion (Estimated): January 1, 2034
• Last Updated: February 2, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)