Sponsor: Can-Fite BioPharma (industry)
Phase: 3
Start date: March 15, 2023
Planned enrollment: 471
Namodenoson (CF102; Cl-IB-MECA) is an oral, highly selective adenosine A3 receptor (A3AR) agonist being developed primarily for liver diseases, including hepatocellular carcinoma (HCC) and metabolic dysfunction–associated steatohepatitis (MASH/NASH). It has completed a randomized phase II trial in advanced HCC with Child-Pugh B (CPB) cirrhosis and a randomized phase II trial in NAFLD/NASH; a global phase III trial in CPB7 HCC is ongoing. (pubmed.ncbi.nlm.nih.gov)
Hepatocellular carcinoma (advanced; CPB)
Phase II randomized, double-blind, placebo-controlled study (n=78; 25 mg BID vs placebo, second-line): Primary endpoint overall survival (OS) was not met in the intention-to-treat population (median OS 4.1 vs 4.3 months; HR 0.82). In the prespecified CPB7 subgroup (n=56), median OS was 6.9 vs 4.3 months (HR 0.81; not statistically significant by log-rank), and 12‑month OS favored namodenoson (44% vs 18%; p=0.028). Partial responses occurred in 3/34 (8.8%) vs 0/21 (0%) with placebo. Progression‑free survival in CPB7 was 3.5 vs 1.9 months (HR 0.89; not significant). (pubmed.ncbi.nlm.nih.gov)
Earlier open‑label phase I/II dose‑escalation study in advanced HCC (n=18) showed acceptable pharmacokinetics and safety, with median OS 7.8 months overall and 8.1 months in CPB patients; disease stabilization was observed in some participants. These findings supported further study. (theoncologist.onlinelibrary.wiley.com)
Ongoing pivotal phase III (LIVERATION; CPB7 HCC; randomized, double‑blind, placebo‑controlled) is recruiting; primary endpoint OS. Estimated primary completion February 2026. (ichgcp.net)
NAFLD/NASH (now MASLD/MASH)
Phase II randomized, double-blind study in NAFLD with or without NASH (n=60; 12.5 or 25 mg BID vs placebo for 12 weeks): Dose‑related reductions in aminotransferases; AST change from baseline significantly favored 25 mg vs placebo at week 12 (p=0.03). ALT normalization at week 16 occurred in 36.8% (25 mg) vs 10.0% (placebo; p=0.038). Signals for improvement in noninvasive fibrosis/steatosis metrics were reported. (pubmed.ncbi.nlm.nih.gov)
A phase IIb, biopsy‑driven MASH trial is underway (multicenter, randomized, double-blind, 25 mg BID vs placebo for 36 weeks; histologic primary endpoint). (ir.canfite.com)
In advanced HCC phase II, namodenoson was generally well tolerated with a safety profile comparable to placebo; no treatment‑related deaths and no withdrawals due to toxicity were reported. Reported adverse events were mostly grade 1–2. (pubmed.ncbi.nlm.nih.gov)
In NAFLD/NASH phase II, both doses were well tolerated with no drug‑emergent severe adverse events, hepatotoxicity, or deaths; possibly related events were infrequent (e.g., myalgia, muscular weakness, headache). (pubmed.ncbi.nlm.nih.gov)
Notes: The ongoing development programs and timelines reflect records last updated April 2025 for the phase III HCC trial; definitive efficacy for registration awaits completion of that study. (ichgcp.net)
Last updated: Oct 2025
Goal: Evaluate whether namodenoson improves overall survival and clinical outcomes versus placebo, and assess safety, in previously treated advanced hepatocellular carcinoma with Child-Pugh B7 cirrhosis.
Patients: Adults with advanced, non-curable HCC (BCLC B or C) whose disease progressed after 1–2 prior systemic regimens; measurable disease by RECIST v1.1; ECOG 0–1; strictly Child-Pugh B7 cirrhosis; adequate hematologic and organ function; no hepatic encephalopathy, recent major bleeding, or significant uncontrolled cardiac disease.
Design: Multicenter, phase 3, randomized, double-blind, placebo-controlled study with 2:1 allocation to investigational drug or placebo. Continuous 28-day cycles until progression or unacceptable toxicity. Imaging every two cycles; safety assessed regularly. Long-term survival follow-up for all consenting randomized patients; option for open-label namodenoson after unblinding for ongoing survivors on blinded therapy.
Treatments: Namodenoson 25 mg orally twice daily versus matching placebo, continued until disease progression or unacceptable adverse events. Namodenoson (CF102; Cl-IB-MECA) is an oral, highly selective adenosine A3 receptor agonist, a target often overexpressed in tumors and inflamed liver tissue. Proposed antitumor and anti-inflammatory effects involve modulation of PI3K/AKT, NF-κB, and Wnt/β-catenin pathways leading to apoptosis and reduced proliferation/inflammation. Prior randomized phase II data in second-line advanced HCC with Child-Pugh B did not meet the overall survival primary endpoint in the intent-to-treat population but showed a prespecified signal in the CPB7 subgroup and a favorable safety profile; additional phase II data in NAFLD/NASH demonstrated biochemical improvements and good tolerability.
Outcomes: Primary: Overall survival. Key secondary: Progression-free survival by RECIST and mRECIST, objective response rate, safety and tolerability (CTCAE v5), and pharmacokinetics. Other outcomes include duration of response, disease control rate, and quality of life by EORTC QLQ-C30 and QLQ-HCC18.
Burden on patient: Moderate. The regimen is oral and administered at home, reducing infusion visits. Study visits include safety assessments and imaging every two cycles (approximately every 8 weeks), which is comparable to standard oncology follow-up. There are no protocol-mandated tumor biopsies, but pharmacokinetic sampling occurs over the first 29 days, adding blood draws. Exclusions and monitoring for comorbid hepatic and cardiac conditions necessitate regular labs and clinical evaluations. Travel frequency aligns with imaging and safety visit schedules typical for phase 3 oral systemic therapy in advanced HCC.
Last updated: Oct 2025
Inclusion Criteria:
1. Males and females at least 18 years of age.
2. Diagnosis of HCC:
* For patients without cirrhosis at the time of diagnosis, histologic confirmation is required (archival tissue is acceptable).
* For patients with underlying cirrhosis at the time of diagnosis, diagnosis of HCC established according to the American Association for the Study of Liver Diseases Practice Guideline algorithm (Marrero 2018).
3. HCC is advanced (i.e., treatment-refractory or metastatic) and no standard therapies are expected to be curative.
4. HCC has progressed on at least 1, but no more than 2, prior systemic treatment regimens; prior locoregional therapy is allowed.
5. Barcelona Clinic Liver Cancer (BCLC) Stage B or C (Llovet 1999).
6. Prior HCC treatment was discontinued for at least 2 weeks prior to the Baseline Visit.
7. Measurable disease by RECIST v1.1 (Eisenhauer 2009).
8. ECOG PS of ≤ 1.
9. Cirrhosis classified as CPB7; if ascites is used as a scoring criterion, it must be classified as Grade ≥2 by the Clinical Practice Guidelines of the European Association for the Study of the Liver (EASL 2010).
10. The following laboratory values must be documented within ten days prior to the first dose of study drug:
* Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
* Platelet count at least 75 × 10\^9/L
* Creatinine clearance at least 50 mg/dL (estimated glomerular filtration rate by the Cockcroft-Gault or the Modification of Diet in Renal Disease methods)
* AST and ALT ≤ 5 × the upper limit of normal (ULN)
* Total bilirubin ≤ 3.0 mg/dL
* Serum albumin ≥ 2.8 g/dL.
11. Life expectancy of ≥ 6 weeks.
12. For women of childbearing potential, negative serum pregnancy test result.
13. Provide written informed consent to participate.
14. Willing to comply with scheduled visits, treatment plans, laboratory assessments, and other trial-related procedures.
Exclusion Criteria:
1. Receipt of \>2 prior systemic drug therapies for HCC.
2. Receipt of systemic cancer therapy, immunomodulatory drug therapy, immunosuppressive therapy, or corticosteroids \> 20 mg/day prednisone or equivalent within 14 days prior to the Baseline Visit or concurrently during the trial.
3. Locoregional treatment within 4 weeks prior to the Baseline Visit.
4. Major surgery or radiation therapy within 4 weeks prior to the Baseline Visit.
5. Use of any investigational agent within 4 weeks prior to the Baseline Visit.
6. Concomitant use of P-glycoprotein (P-gp)/breast cancer resistance protein (BCRP) inhibitors and/or substrates with a narrow therapeutic index unless the medication can be taken at least 3 hours before or after taking the investigational product (see Section 12.2).
7. Child-Pugh Class A, B8/9, or C cirrhosis.
8. Hepatic encephalopathy.
9. Occurrence of esophageal or other gastrointestinal hemorrhage requiring transfusion within 4 weeks prior to the Baseline Visit.
10. Uncontrolled or clinically unstable thyroid disease, per judgment of the Principal Investigator.
11. Active bacterial, viral, or fungal infection requiring systemic therapy or operative or radiological intervention.
12. Known human immunodeficiency virus- or acquired immunodeficiency syndrome-related illness.
13. Liver transplant.
14. Active malignancy other than HCC.
15. Uncontrolled arterial hypertension or congestive heart failure (New York Heart Association Classification 3 or 4).
16. Angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of study drug.
17. History of, or ongoing, cardiac dysrhythmias requiring treatment, atrial fibrillation of any grade, or persistent prolongation of the QTc (Fridericia) interval to \> 470 msec (patients with bundle branch block will not be excluded for QTc reasons).
18. Pregnant or lactating female.
19. Women of childbearing potential, unless they agree to use dual contraceptive methods which, in the opinion of the Investigator, are effective and adequate for the patient's circumstances while on study drug.
20. Men who partner with a woman of childbearing potential, unless they agree to use effective, dual contraceptive methods (i.e., a condom, with female partner using oral, injectable, or barrier method) while on study drug and for 3 months afterward.
21. Any severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with trial participation or study drug administration; may interfere with the informed consent process and/or with compliance with the requirements of the trial; or may interfere with the interpretation of trial results and, in the Investigator's opinion, would make the patient inappropriate for entry into this trial.
Sarajevo, Bosnia and Herzegovina
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Banja Luka, Bosnia and Herzegovina
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Mostar, Bosnia and Herzegovina
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Sofia, Bulgaria
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Burgas, Bulgaria
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Plovdiv, Bulgaria
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Plovdiv, Bulgaria
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Petah Tikva, Israel
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Chisinau, Moldova
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Warsaw, Poland
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Koszalin, Poland
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Krakow, Poland
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Mysłowice, Poland
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Przemyśl, Poland
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Wroclaw, Poland
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Timișoara, Romania
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Cluj-Napoca, Romania
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Status: Recruiting
Cluj-Napoca, Romania
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Status: Not yet recruiting
Constanța, Romania
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Craiova, Romania
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Craiova, Romania
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Status: Recruiting
Iași, Romania
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Status: Recruiting
Iași, Romania
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Status: Recruiting
Oradea, Romania
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Timișoara, Romania
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Status: Recruiting
Kladovo, Serbia
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Status: Not yet recruiting
Belgrade, Serbia
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Status: Not yet recruiting
Kamenitz, Serbia
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Kragujevac, Serbia
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Status: Not yet recruiting
Košice, Slovakia
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Status: Not yet recruiting
Banská Bystrica, Slovakia
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Status: Not yet recruiting
Dallas, Texas, 75201, United States
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Status: Not yet recruiting