Namodenoson in advanced hepatocellular carcinoma and child–pugh B cirrhosis: Randomized placebo-controlled clinical trial

Salomon M. Stemmer, Nebojsa S. Manojlovic, Mihai Vasile Marinca, Petar Petrov, Nelly Cherciu, Doina Ganea, Tudor Eliade Ciuleanu, Ioana Adriana Pusca, Muhammad Shaalan Beg, William T. Purcell, Adina Emilia Croitoru, Rumyana Nedyalkova Ilieva, Sladjana Natošević, Amedeia Lavinir Nita, Dimitar Nikolaev Kalev, Zivit Harpaz, Motti Farbstein, Michael H. Silverman, David Bristol, Inbal ItzhakPnina Fishman

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number187
Pages (from-to)1-12
Number of pages12
JournalCancers
Volume13
Issue number2
DOIs
StatePublished - Jan 2 2021

Keywords

  • Child–Pugh B
  • Hepatocellular carcinoma
  • Namodenoson
  • Overall survival
  • Randomized clinical trial

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Namodenoson in advanced hepatocellular carcinoma and child–pugh B cirrhosis: Randomized placebo-controlled clinical trial'. Together they form a unique fingerprint.

Cite this