Phase II study of temozolomide and veliparib combination therapy for sorafenib-refractory advanced hepatocellular carcinoma

PURPOSE: To determine the antitumor efficacy and tolerability of combination temozolomide (TMZ) and veliparib (ABT-888) in patients with advanced, sorafenib-refractory hepatocellular carcinoma (HCC). METHODS: This single-arm phase II trial enrolled patients with pathologically confirmed, sorafenib-refractory HCC. All patients received 40 mg ABT-888 PO daily on days 1–7 and 150 mg/m(2) TMZ PO daily on days 1–5 of a 28-day cycle. The primary endpoint was objective response rate (ORR) at 2 months. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and toxicity profile. Tumor response was assessed every 2 cycles using RECIST criteria, and toxicities were assessed using CTCAE v4.03. RESULTS: We enrolled 16 patients in the first phase of the trial, but the study was discontinued due to a poor ORR; only four patients (25 %) had SD after 2 cycles. Twelve patients (75 %) were taken off study after 2 months of treatment; 10 of these had disease progression. Two patients (13 %) were taken off study due to severe toxicity, and one patient (6 %) died from non-treatment-related liver failure. One patient had SD for 16 months, receiving 11 cycles of therapy before being taken off study. The most common grade 3 treatment-related toxicities included vomiting (n = 2), thrombocytopenia (n = 2), nausea (n = 1), and anemia (n = 1). The median PFS was 1.9 months, and median OS was 13.1 months. CONCLUSION: The combination of TMZ and ABT-888 is well tolerated in patients with advanced HCC. However, the regimen failed to show survival benefit. CLINICALTRIALS.GOV IDENTIFIER: NCT01205828. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00280-015-2852-2) contains supplementary material, which is available to authorized users.