Hepatic Arterial Infusion of Gemcitabine-oxaliplatin for Second-line Therapy in Non-metastatic Unresectable Intra-hepatic Cholangiocarcinoma — GEMOXIA-02  

Cholangiocarcinoma Non-resectable Clinical Trial

Official title: Hepatic Arterial Infusion of Gemcitabine-oxaliplatin for Second-line Therapy in Non-metastatic Unresectable Intra-hepatic Cholangiocarcinoma: a Multicentric Single-arm Phase II Study

Status Recruiting

Clinical Trial Summary

We hypothesized that intra-arterial gemcitabine/oxaliplatin administered as second-line treatment could strongly improve objective response rate at 4 months after inclusion in patient with non-metastatic unresectable intra-hepatic cholangiocarcinoma.

Clinical Trial Description

Cholangiocarcinomas are rare tumors with an extremely poor prognosis. The best therapeutic option (i.e. resection) can only be done in 20% of cases. Combinations of gemcitabine/platinum compounds were identified as the new standard first-line therapy

For patients with hepatic-only disease, therapy intensification using Intra-Arterial (IA) chemotherapy could be an attractive option since:

• Vascularisation of hepatic tumors is almost exclusively provided by the hepatic artery.

• Gemcitabine and oxaliplatin have a high rate of hepatic extraction during the first passage, thus allowing the drugs to reach high intra-tumoral concentrations with low systemic toxicity.

• The plasma concentration of gemcitabine after IA injection is 1/7th of that observed following Intra-Venous (IV) injection. No grade 3-4 toxicity has been observed in doses <1400mg/m².

• Phase I and I/II studies have shown dose-limiting toxicity between 150-175mg/m² for IA oxaliplatin every 3 weeks.

• We reported (Ghiringhelli, Chemotherapy 2013) in 12 patients with progressive intra-hepatic cholangiocarcinoma after IV gemcitabine/oxaliplatin, a partial response in 8 cases (stability in 3 cases) after IA gemcitabine/oxaliplatin. Among them, two were resected (R0) and three were treated by stereotactic radiation therapy).

Hepatic IA chemotherapy has rarely been used for the treatment of intra-hepatic cholangiocarcinoma (IHC), essentially in case-reports from Asia and in a few case-series that have mainly used IA monotherapy. The implantation of a hepatic arterial catheter has now been mastered by interventional radiologists and makes it possible to increase the intra-tumoral concentration of the drugs and probably to limit their systemic toxicity.

Very recently, we have reported that this combination in progressive IHC following systemic gemcitabine/oxaliplatin has led to partial responses and allowed certain patients to benefit from curative treatment.

This suggests that the intra-arterial approach increases the efficacy of these 2 drugs. For locally-advanced IHC, such a loco-regional approach is worth exploring in this poor-prognosis tumor, especially since so far 1) there is insufficient evidence to recommend a second-line chemotherapy schedule in this tumor and 2) targeted therapies have demonstrated no survival benefit over systemic chemotherapy alone.

It is a multicenter single-arm phase II trial aiming to determine the objective response rate 4 months after inclusion following IA gemcitabine / oxaliplatin administered as second-line treatment in patients with non-metastatic unresectable intra-hepatic cholangiocarcinoma.

It will be the first French phase II trial for 2nd line treatment in intrahepatic cholangiocarcinoma. ;

Related Conditions & MeSH terms

• Cholangiocarcinoma
• Cholangiocarcinoma Non-resectable
• Non-metastatic

• NCT number: NCT03364530
• Study type: Interventional
• Source: University Hospital, Montpellier
• Contact: Chloé Guillot
• Phone: +33467337327
• Email: chloe-guillot@chu-montpellier.fr
• Status: Recruiting
• Phase: Phase 2
• Start date: June 11, 2018
• Completion date: June 10, 2025