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

NCT ID: NCT05201404

Last Updated: 2025-04-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 471 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-15
• Study Completion Date: 2026-10-31

Brief Summary

This is a clinical trial in patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh Class B7 (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.

Detailed 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.

Conditions

Hepatocellular Carcinoma; Cirrhosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Namodenoson (CF102)

Namodenoson 25 mg orally BID, until disease progression or unacceptable adverse events

Group Type: EXPERIMENTAL

Namodenoson

Intervention Type: DRUG

Adenosine A3 Receptor (A3AR) agonist

Placebo

Matching placebo orally BID, until disease progression or unacceptable adverse events

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Control arm

Interventions

Namodenoson

Adenosine A3 Receptor (A3AR) agonist

Intervention Type: DRUG

Placebo

Control arm

Intervention Type: DRUG

Other Intervention Names

CF102; Inactive control

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Can-Fite BioPharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael H Silverman, MD

Role: STUDY_DIRECTOR

BioStrategics Consulting Ltd

Locations

Site 881

Dallas, Texas, United States

Site Status: NOT_YET_RECRUITING

841 University Clinical Centre of Republic of Srpska

Banja Luka, , Bosnia and Herzegovina

Site Status: NOT_YET_RECRUITING

843 University Clinical Hospital Mostar

Mostar, , Bosnia and Herzegovina

Site Status: NOT_YET_RECRUITING

842 University Clinical Centre Sarajevo

Sarajevo, , Bosnia and Herzegovina

Site Status: NOT_YET_RECRUITING

831 Dept of Medical Oncology, Complex Oncology Ctr - Burgas EOOD

Burgas, , Bulgaria

Site Status: NOT_YET_RECRUITING

835 First Department of Medical Oncology, Gastroenterology and Pulmology, Complex Oncology Center - Plovdiv EOOD, Plovdiv

Plovdiv, , Bulgaria

Site Status: NOT_YET_RECRUITING

Medical Center Leo Clinic EOOD Plovdiv

Plovdiv, , Bulgaria

Site Status: NOT_YET_RECRUITING

834 Medical Oncology Dept, Univ Multiprofile Hospital for Active Treatment "Sv. Ivan Rilski" EAD, Sofia

Sofia, , Bulgaria

Site Status: RECRUITING

518 Rabin Medical Center Beilinson Hospital

Petah Tikva, , Israel

Site Status: RECRUITING

872 IMSP Institute of Oncology

Chisinau, , Moldova

Site Status: RECRUITING

Site 858

Koszalin, , Poland

Site Status: NOT_YET_RECRUITING

Site 852

Krakow, , Poland

Site Status: NOT_YET_RECRUITING

Site 857

Mysłowice, , Poland

Site Status: NOT_YET_RECRUITING

Site 859

Przemyśl, , Poland

Site Status: NOT_YET_RECRUITING

Site 855

Warsaw, , Poland

Site Status: NOT_YET_RECRUITING

Site 850

Wroclaw, , Poland

Site Status: NOT_YET_RECRUITING

802 Institutul Regional de Gastroenterologie si Hepatologie

Cluj-Napoca, , Romania

Site Status: RECRUITING

807 IOCN, Medical Oncology

Cluj-Napoca, , Romania

Site Status: NOT_YET_RECRUITING

809 Spitalul Clinic Judetean de Urgenta Constanta Oncology Dept

Constanța, , Romania

Site Status: NOT_YET_RECRUITING

801 Oncology Center "Sf. Nectarie" Medical Oncology

Craiova, , Romania

Site Status: RECRUITING

803 Oncolab SRL

Craiova, , Romania

Site Status: RECRUITING

805 Euroclinic lasi

Iași, , Romania

Site Status: RECRUITING

810 IRO Iasi-Clinica Oncologie Medicala

Iași, , Romania

Site Status: RECRUITING

808 Spitalul Clinic Pelican Oradea Oncology Department

Oradea, , Romania

Site Status: RECRUITING

804 Oncomed - Medical Oncology

Timișoara, , Romania

Site Status: RECRUITING

806 Oncocenter Oncologie Clinica SRL

Timișoara, , Romania

Site Status: RECRUITING

821 Clinic for Gastroenterology and Hepatology, Military Medical Academy

Belgrade, , Serbia

Site Status: NOT_YET_RECRUITING

822 Oncology Institute of Vojvodina

Kamenitz, , Serbia

Site Status: NOT_YET_RECRUITING

823 Oncology Department, Health Center Kladovo

Kladovo, , Serbia

Site Status: NOT_YET_RECRUITING

824 Univ Clin Centre Kragujevac, Dept of Oncology

Kragujevac, , Serbia

Site Status: NOT_YET_RECRUITING

Site 867

Banská Bystrica, , Slovakia

Site Status: NOT_YET_RECRUITING

Site 865

Košice, , Slovakia

Site Status: NOT_YET_RECRUITING

Countries

United States; Bosnia and Herzegovina; Bulgaria; Israel; Moldova; Poland; Romania; Serbia; Slovakia

Central Contacts

Zivit Harpaz

Role: CONTACT

Zivit@canfite.co.il

+972 3 924 1114

Facility Contacts

Study Coordinator

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Study Coordinator

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Study Coordinator

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Salomon Stemmer, MD

Role: primary

Study Coordinator

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References

Bar-Yehuda S, Stemmer SM, Madi L, Castel D, Ochaion A, Cohen S, Barer F, Zabutti A, Perez-Liz G, Del Valle L, Fishman P. The A3 adenosine receptor agonist CF102 induces apoptosis of hepatocellular carcinoma via de-regulation of the Wnt and NF-kappaB signal transduction pathways. Int J Oncol. 2008 Aug;33(2):287-95.

Reference Type: BACKGROUND

PMID: 18636149 (View on PubMed)

Cohen S, Stemmer SM, Zozulya G, Ochaion A, Patoka R, Barer F, Bar-Yehuda S, Rath-Wolfson L, Jacobson KA, Fishman P. CF102 an A3 adenosine receptor agonist mediates anti-tumor and anti-inflammatory effects in the liver. J Cell Physiol. 2011 Sep;226(9):2438-47. doi: 10.1002/jcp.22593.

Reference Type: BACKGROUND

PMID: 21660967 (View on PubMed)

Stemmer SM, Benjaminov O, Medalia G, Ciuraru NB, Silverman MH, Bar-Yehuda S, Fishman S, Harpaz Z, Farbstein M, Cohen S, Patoka R, Singer B, Kerns WD, Fishman P. CF102 for the treatment of hepatocellular carcinoma: a phase I/II, open-label, dose-escalation study. Oncologist. 2013;18(1):25-6. doi: 10.1634/theoncologist.2012-0211. Epub 2013 Jan 8.

Reference Type: BACKGROUND

PMID: 23299770 (View on PubMed)

Stemmer SM, Manojlovic NS, Marinca MV, Petrov P, Cherciu N, Ganea D, Ciuleanu TE, Pusca IA, Beg MS, Purcell WT, Croitoru AE, Ilieva RN, Natosevic S, Nita AL, Kalev DN, Harpaz Z, Farbstein M, Silverman MH, Bristol D, Itzhak I, Fishman P. Namodenoson in Advanced Hepatocellular Carcinoma and Child-Pugh B Cirrhosis: Randomized Placebo-Controlled Clinical Trial. Cancers (Basel). 2021 Jan 7;13(2):187. doi: 10.3390/cancers13020187.

Reference Type: BACKGROUND

PMID: 33430312 (View on PubMed)

Related Links

https://www.canfite.com/

Sponsor website

Other Identifiers

CF102-301HCC

Identifier Type: -

Identifier Source: org_study_id