Namodenoson in Advanced Hepatocellular Carcinoma and Child–Pugh B Cirrhosis: Randomized Placebo-Controlled Clinical Trial

Stemmer, Salomon M. and Manojlovic, Nebojsa S. and Marinca, Mihai Vasile and Petrov, Petar and Cherciu, Nelly and Ganea, Doina and Ciuleanu, Tudor Eliade and Pusca, Ioana Adriana and Beg, Muhammad Shaalan and Purcell, William T. and Croitoru, Adina-Emilia and Ilieva, Rumyana Nedyalkova and Natošević, Sladjana and Nita, Amedeia Lavinir and Kalev, Dimitar Nikolaev and Harpaz, Zivit and Farbstein, Motti and Silverman, Michael H. and Bristol, David and Itzhak, Inbal and Fishman, Pnina (2021) Namodenoson in Advanced Hepatocellular Carcinoma and Child–Pugh B Cirrhosis: Randomized Placebo-Controlled Clinical Trial. Cancers, 13 (2). p. 187. ISSN 2072-6694

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Abstract

Namodenoson, an A3 adenosine-receptor agonist, showed promising results in advanced hepatocellular carcinoma (HCC) and moderate hepatic dysfunction (Child–Pugh B; CPB) in a phase I/II clinical study. This phase II study investigated namodenoson as second-line therapy in such patients. Patients were randomized 2:1 to twice a day (BID) namodenoson (25 mg; n = 50) or placebo (n = 28). The primary endpoint (overall survival [OS]) was not met. Median OS was 4.1/4.3 months for namodenoson/placebo (hazard ratio [HR], 0.82; 95% confidence interval [CI] 0.49–1.38; p = 0.46). Pre-planned subgroup analysis of CPB7 patients (34 namodenoson-treated, 22 placebo-treated) showed a nonsignificant improvement in OS/progression-free survival (PFS). OS: 6.9 versus 4.3 months; HR, 0.81; 95% CI: 0.45–1.43, p = 0.46. PFS: 3.5 versus 1.9 months; HR, 0.89; 95% CI: 0.51–1.55, p = 0.67 (log-rank test). The difference in 12-month OS was significant (44% versus 18%, p = 0.028). Response rates were determined in patients for whom ≥ 1 assessment post-baseline was available (34 namodenoson-treated, 21 placebo-treated). Partial response was achieved by 3/34 (8.8%) and 0/21 (0%) patients, respectively. Namodenoson was well-tolerated, with a safety profile comparable to that of the placebo group. No treatment-related deaths were reported; no patients withdrew due to toxicity. In conclusion, namodenoson demonstrated a favorable safety profile and a preliminary efficacy signal in HCC CPB.

Item Type: Article
Subjects: Science Repository > Medical Science
Depositing User: Managing Editor
Date Deposited: 06 Feb 2023 04:32
Last Modified: 02 Apr 2024 05:31
URI: http://research.manuscritpub.com/id/eprint/1567

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