The majority of patients with intrahepatic cholangiocarcinoma (CCA) present with advanced liver disease and are not candidates for curative resection. The current standard of care for patients with unresectable intrahepatic CCA is palliative chemotherapy with gemcitabine plus cisplatin. Alternatively, hepatic arterial infusion (HAI) using a surgically implanted pump provides continuous liver-directed therapy for maximal exposure, while limiting systemic side effects and facilitating conversion to a resectable status. In particular, HAI therapy with floxuridine and dexamethasone may be a viable treatment alternative in this setting.
The HELIX-ICC is a first-line, single-center, single-arm, phase 2 clinical trial that is evaluating a dose-reduced HAI of floxuridine protocol in combination with modified systemic regimens to facilitate control of liver disease and maximize patient quality of life (QOL) in patients with unresectable intrahepatic CCA. At the 2022 ASCO GI Cancers Symposium, Brett S. Walker, MD, Oregon Health & Science University, Portland, described this study.
The primary objectives of the HELIX-ICC study are to evaluate the safety and disease control rate at 4 months. The secondary end points include overall response rate, disease control rate after period 1, disease control rate over the entire study period, 1-year overall survival, and progression-free survival. Exploratory end points include evaluation of QOL and radiographic response, characterization of tumor-derived circulating hybrid cells, patterns of microRNA expression, and the effect on the patient’s immune microenvironment.
The key inclusion criteria include liver-dominant unresectable or multifocal intrahepatic CCA, <70% liver parenchymal involvement, and ECOG performance status ≤1. Patients with liver radiotherapy, extrahepatic CCA, previous use of the FOLFOX or the FOLFIRINOX regimen, significant liver dysfunction, biliary obstruction requiring stenting, and microsatellite instability-high cancer are excluded.
Eligible patients will receive the dose-modified FOLFIRINOX regimen as first-line therapy for 4 cycles over 8 weeks. Patients with evidence of disease control from restaging imaging and laparoscopy will proceed to HAI pump placement. Treatment will continue with two 28-day cycles of combined HAI floxuridine (1.08 mg/kg) plus dexamethasone for 14 days and a systemic dose-modified FOLFIRI regimen starting on day 15.
The investigators plan to enroll 30 patients, with an initial safety run-in of 6 patients. This study is designed to allow for drop out of 9 patients, with a total accrual of 21 patients to achieve 80.2% power at 0.05 significance to detect a 25% increase in disease control rate at 6 months. At the time of the study presentation, 4 patients had been enrolled in the study.
Walker BS, Kardosh A, Eil R, et al. HELIX-ICC: an-open label phase II trial of induction systemic mFOLFIRINOX followed by concurrent hepatic arterial infusion of floxuridine and systemic mFOLFIRI for unresectable intrahepatic cholangiocarcinoma. Abstract TPS500.
To sign up for our newsletter or print publications, please enter your contact information below.
