Combining liver-directed therapy (HAI pump or SIRT) with GemOx chemotherapy for unresectable intrahepatic cholangiocarcinoma (TOMCAT)

Trans-arterial Treatment of Patients With Intra-hepatic Cholangiocarcinoma Not Amenable to Resection (TOMCAT)

This trial will test whether adding a liver-directed treatment (either a hepatic artery infusion pump delivering floxuridine or selective internal radiation therapy) to GemOx chemotherapy helps shrink or control intrahepatic cholangiocarcinoma that cannot be removed by surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 39 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Oslo University Hospital (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Oslo, Oslo)
• Trial ID: NCT06313203 on ClinicalTrials.gov

What this trial studies

This phase 2, parallel-cohort study assigns patients with unresectable intrahepatic cholangiocarcinoma to one of two liver-directed approaches combined with systemic GemOx chemotherapy: hepatic artery infusion (HAI) with floxuridine and dexamethasone, or selective internal radiation therapy (SIRT). Assignment depends on tumor characteristics, disease stage, and patient ability/preferences, with HAI requiring a surgically implanted pump and frequent fortnightly visits to Oslo and SIRT requiring a specialized work-up and treatment at the same center. Eligible patients have biopsy-confirmed disease largely confined to the liver (or limited resectable porta hepatis nodes), measurable lesions >2 cm, and ECOG performance status 0–1 and must be able to tolerate GemOx. The study measures safety, radiologic response, and the potential to down-stage tumors to allow curative resection.

Who should consider this trial

Good fit: Adults with biopsy-confirmed intrahepatic cholangiocarcinoma not eligible for upfront resection, disease largely confined to the liver or with limited resectable porta hepatis nodes, measurable lesion >2 cm, ECOG 0–1, able to tolerate GemOx, and able/willing to travel to Oslo if selected for HAI or SIRT.

Not a fit: Patients with widespread extrahepatic disease, poor performance status (ECOG ≥2), lesions unsuitable for liver-directed therapy, or who cannot travel to Oslo for repeated HAI or SIRT visits are unlikely to benefit.

Why it matters

Potential benefit: If successful, the approach could improve liver tumor control, increase the chance of down-staging to surgery, and extend survival for some patients.

How similar studies have performed: Small series and institutional reports, including MSKCC data, have suggested a clinical benefit from adding intrahepatic chemotherapy to systemic therapy, but randomized evidence in intrahepatic cholangiocarcinoma is limited and HAI-FUDR/DEX is not widely approved.

Eligibility criteria

Inclusion Criteria:

1. Intra-hepatic cholangiocarcinoma. Diagnosis confirmed by biopsy, cytology or previous resection.
2. Not amenable for upfront resection. Defined as:

   1. 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.
   2. Any multifocality (more than one tumour) irrespective of distance between assumed primary and other lesions
   3. Recurrent tumour following resection
   4. Radiologically or cytology-proven malignant regional lymph nodes
3. Disease confined to the liver or associated with limited, resectable porta hepatis lymph node metastases
4. Radiologically measurable disease with at least one lesion \> 2 cm in greatest diameter
5. Physical performance score WHO/ECOG stage 0/1
6. Age \> 18 years
7. Assumed ability to tolerate at least one full cycle of GemOx
8. For eligibility to HAI-FUDR/DEX treatment, patients must be willing and able to go to Oslo every fortnight
9. 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.

Exclusion Criteria:

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

Where this trial is running

Oslo, Oslo

• Oslo University Hospital — Oslo, Oslo, Norway (Recruiting)

Conditions Intrahepatic Cholangiocarcinoma; Chemotherapy Effect