title: CF102 for the treatment of hepatocellular carcinoma: a phase I/II, open-label, dose-escalation study.
abstract: BACKGROUND
  The A(3) adenosine receptor (A(3)AR) is overexpressed in the tumor and in the peripheral blood mononuclear cells of patients with hepatocellular carcinoma (HCC). The orally active drug candidate CF102, an A(3)AR agonist, induces apoptosis of HCC cells via deregulation of the Wnt signaling pathway. In this open label phase I/II trial, the safety and clinical effects of CF102 were assessed in patients with advanced unresectable HCC.
  
  
  METHODS
  The primary objectives of this trial were to examine the safety and pharmacokinetic (PK) behavior of CF102 given orally (1, 5, and 25 mg BID) in 28-day cycles. Evaluation of anti-tumor effects and the utilization of A(3)AR as a biological predictive marker of response to CF102 were the secondary objectives.
  
  
  RESULTS
  Eighteen patients received CF102-six at each dose level. No serious drug-related adverse events or dose-limiting toxicities were observed. CF102 demonstrated good oral bioavailability and linear PK behavior. Median overall survival in the study population, 67% of whom had received prior sorafenib, was 7.8 months, and for Child Pugh B patients (28%) it was 8.1 months. Stable disease by RECIST was observed in four patients for at least 4 months. CF102 maintained liver function over a 6-month period. A correlation between receptor overexpression levels at baseline and patients' overall survival was found. One of the patients who presented with skin nodules that were biopsy-proven to be HCC metastases prior to the trial showed complete metastasis regression during three months of treatment with CF102.
  
  
  CONCLUSIONS
  CF102 is safe and well-tolerated, showing favorable PK characteristics in Child Pugh A and B HCC patients, justifying further clinical development.
authors.affiliation: Can-Fite BioPharma, 10 Bareket Street, P.O.Box 7537, Petach-Tikva 49170, Israel.
authors.forename: Salomon M
authors.initials: SM
authors.lastname: Stemmer
authors.forename: Ofer
authors.initials: O
authors.lastname: Benjaminov
authors.forename: Gal
authors.initials: G
authors.lastname: Medalia
authors.forename: Noab B
authors.initials: NB
authors.lastname: Ciuraru
authors.forename: Michael H
authors.initials: MH
authors.lastname: Silverman
authors.forename: Sara
authors.initials: S
authors.lastname: Bar-Yehuda
authors.forename: Sari
authors.initials: S
authors.lastname: Fishman
authors.forename: Zivit
authors.initials: Z
authors.lastname: Harpaz
authors.forename: Motti
authors.initials: M
authors.lastname: Farbstein
authors.forename: Shira
authors.initials: S
authors.lastname: Cohen
authors.forename: Renana
authors.initials: R
authors.lastname: Patoka
authors.forename: Barak
authors.initials: B
authors.lastname: Singer
authors.forename: William D
authors.initials: WD
authors.lastname: Kerns
authors.forename: Pnina
authors.initials: P
authors.lastname: Fishman
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D002648:Child; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D058906:Purinergic P1 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D043684:Receptor, Adenosine A3 / Q000378:metabolism; D000077157:Sorafenib; D060449:Wnt Signaling Pathway
chemical_list: D010671:Phenylurea Compounds; D058906:Purinergic P1 Receptor Agonists; D043684:Receptor, Adenosine A3; D009536:Niacinamide; D000077157:Sorafenib; D000241:Adenosine; C090034:2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide