Holmium-166 radioembolization for the treatment of patients with liver metastases: design of the phase I HEPAR trial

The HEPAR study (Holmium Embolization Particles for Arterial Radiotherapy) is a non-randomized, open label, safety study. We aim to include 15 to 24 patients with liver metastases of any origin, who have chemotherapy-refractory disease and who are not amenable to surgical resection. Prior to treatment, in addition to the standard technetium-99m labelled macroaggregated albumin ( 99mTc-MAA) dose, a low radioactive safety dose of 60-mg 166Ho-PLLA-MS will be administered. Patients are treated in 4 cohorts of 3-6 patients, according to a standard dose escalation protocol (20 Gy, 40 Gy, 60 Gy, and 80 Gy, respectively). The primary objective will be to establish the maximum tolerated radiation dose of 166Ho-PLLA-MS. Secondary objectives are to assess tumour response, biodistribution, performance status, quality of life, and to compare the 166Ho-PLLA-MS safety dose and the 99mTc-MAA dose distributions with respect to the ability to accurately predict microsphere distribution.This will be the first clinical study on 166Ho-RE. Based on preclinical studies, it is expected that 166Ho-RE has a safety and toxicity profile comparable to that of 90Y-RE. The biochemical and radionuclide characteristics of 166Ho-PLLA-MS that enable accurate dosimetry calculations and biodistribution assessment may however improve the overall safety of the procedure.ClinicalTrials.gov NCT01031784The liver is a common site of metastatic disease. Hepatic metastases can originate from a wide range of primary tumours (e.g. colorectal-, breast- and neuroendocrine tumours) [1]. It is estimated that 50% of all patients with a primary colorectal tumour will in due course develop hepatic metastases [2]. Once a primary malignancy has spread to the liver, the prognosis of many of these patients deteriorates significantly. Potentially curative treatment options for hepatic metastases consist of subtotal hepatectomy or, in certain cases, radiofrequency ablation. Unfortunately, only 20-30% of patients are eligible