Namodenoson in the Treatment of Advanced Hepatocellular Carcinoma in Patients With Child-Pugh Class B7 Cirrhosis

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified March 2025 by Can-Fite BioPharma
Sponsor
Can-Fite BioPharma
Information Provided by (Responsible Party)
Can-Fite BioPharma
Clinicaltrials.gov Identifier
NCT05201404
Other Study ID Numbers:
CF102-301HCC
First Submitted
December 20, 2021
First Posted
January 20, 2022
Last Update Posted
April 28, 2025
Last Verified
March 2025

ClinicalTrials.gov processed this data on April 2025. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

This is a multicenter, randomized, double-blind, placebo-controlled clinical trial in patients with advanced HCC and CPB7 cirrhosis whose disease has progressed on at least 1st-line therapy. The trial will evaluate the efficacy and safety of namodenoson as compared to placebo. Patients will be randomly assigned in a 2:1 ratio to treatment with oral doses of either namodenoson 25 mg or matching placebo administered twice daily for consecutive 28-day cycles. Patients will be evaluated regularly for safety. Tumor imaging will be performed every two cycles. Treatment will continue until the patient experiences PD or unacceptable drug-related intolerability. Patients will return for a follow-up visit 28 days after completion of the last dose of study drug, and survival data will be obtained for all randomized patients who consent to long-term follow-up. Patients who discontinue dosing and consent to follow-up will be followed indefinitely for survival status.

Once the requisite number of events has been observed and the blind is broken for analysis of the trial results, any surviving patients who remain on blinded drug will be offered the opportunity to continue dosing with OL namodenoson 25 mg twice daily indefinitely.

Condition or DiseaseIntervention/Treatment
Hepatocellular CarcinomaCirrhosis
Drug: NamodenosonDrug: Placebo

Study Design

Study TypeInterventional
Actual Enrollment471 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleA Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Namodenoson in the Treatment of Advanced Hepatocellular Carcinoma in Patients With Child-Pugh Class B7 Cirrhosis
Study Start DateMarch 14, 2023
Actual Primary Completion DateJanuary 31, 2026
Actual Study Completion Date4mos 1w from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Namodenoson (CF102)
Namodenoson 25 mg orally BID, until disease progression or unacceptable adverse events
Drug: Namodenoson
Adenosine A3 Receptor (A3AR) agonist
Placebo
Matching placebo orally BID, until disease progression or unacceptable adverse events
Drug: Placebo
Control arm

Outcome Measures

Primary Outcome Measures
  1. Overall Survival (OS)
    Median duration of survival
Secondary Outcome Measures
  1. Progression-Free Survival (PFS)
    Median time to disease progression using RECIST and modified RECIST criteria
  2. Objective Response Rate (ORR)
    Proportion of patients who experience Objective Response (OR) using RECIST and modified RECIST criteria
  3. Incidence and nature of treatment-emergent adverse events
    Incidence and nature of treatment-emergent adverse events as assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v5)
  4. Pharmacokinetics (PK) of namodenoson in this population
    Plasma concentration of namodenoson

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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.

Contacts and Locations

Sponsors and CollaboratorsCan-Fite BioPharma
Locations
Site 881 | Dallas Texas, United States, 75201841 University Clinical Centre of Republic of Srpska | Banja Luka , Bosnia and Herzegovina, 843 University Clinical Hospital Mostar | Mostar , Bosnia and Herzegovina, 842 University Clinical Centre Sarajevo | Sarajevo , Bosnia and Herzegovina, 831 Dept of Medical Oncology, Complex Oncology Ctr - Burgas EOOD | Burgas , Bulgaria, 835 First Department of Medical Oncology, Gastroenterology and Pulmology, Complex Oncology Center - Plovdiv EOOD, Plovdiv | Plovdiv , Bulgaria, Medical Center Leo Clinic EOOD Plovdiv | Plovdiv , Bulgaria, 834 Medical Oncology Dept, Univ Multiprofile Hospital for Active Treatment "Sv. Ivan Rilski" EAD, Sofia | Sofia , Bulgaria, 518 Rabin Medical Center Beilinson Hospital | Petah Tikva , Israel, 872 IMSP Institute of Oncology | Chisinau , Moldova, Site 858 | Koszalin , Poland, Site 852 | Krakow , Poland, Site 857 | Mysłowice , Poland, Site 859 | Przemyśl , Poland, Site 855 | Warsaw , Poland, Site 850 | Wroclaw , Poland, 802 Institutul Regional de Gastroenterologie si Hepatologie | Cluj-Napoca , Romania, 807 IOCN, Medical Oncology | Cluj-Napoca , Romania, 809 Spitalul Clinic Judetean de Urgenta Constanta Oncology Dept | Constanța , Romania, 801 Oncology Center "Sf. Nectarie" Medical Oncology | Craiova , Romania, 803 Oncolab SRL | Craiova , Romania, 805 Euroclinic lasi | Iași , Romania, 810 IRO Iasi-Clinica Oncologie Medicala | Iași , Romania, 808 Spitalul Clinic Pelican Oradea Oncology Department | Oradea , Romania, 804 Oncomed - Medical Oncology | Timișoara , Romania, 806 Oncocenter Oncologie Clinica SRL | Timișoara , Romania, 821 Clinic for Gastroenterology and Hepatology, Military Medical Academy | Belgrade , Serbia, 822 Oncology Institute of Vojvodina | Kamenitz , Serbia, 823 Oncology Department, Health Center Kladovo | Kladovo , Serbia, 824 Univ Clin Centre Kragujevac, Dept of Oncology | Kragujevac , Serbia, Site 867 | Banská Bystrica , Slovakia, Site 865 | Košice , Slovakia,
Investigators
Study Director: Michael H Silverman, MD, BioStrategics Consulting Ltd