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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Overall Survival (OS) — From the time of randomization until the date of death from any cause, assessed up to 60 months Median duration of survival
Trial sites (32)
Facility
City
Region
Status
Site 881
Dallas
Texas
Not Yet Recruiting
841 University Clinical Centre of Republic of Srpska
Banja Luka
Bosnia and Herzegovina
Not Yet Recruiting
843 University Clinical Hospital Mostar
Mostar
Bosnia and Herzegovina
Not Yet Recruiting
842 University Clinical Centre Sarajevo
Sarajevo
Bosnia and Herzegovina
Not Yet Recruiting
831 Dept of Medical Oncology, Complex Oncology Ctr - Burgas EOOD
Burgas
Bulgaria
Not Yet Recruiting
835 First Department of Medical Oncology, Gastroenterology and Pulmology, Complex Oncology Center - Plovdiv EOOD, Plovdiv
Plovdiv
Bulgaria
Not Yet Recruiting
Medical Center Leo Clinic EOOD Plovdiv
Plovdiv
Bulgaria
Not Yet Recruiting
834 Medical Oncology Dept, Univ Multiprofile Hospital for Active Treatment "Sv. Ivan Rilski" EAD, Sofia
Sofia
Bulgaria
Recruiting
518 Rabin Medical Center Beilinson Hospital
Petah Tikva
Israel
Recruiting
872 IMSP Institute of Oncology
Chisinau
Moldova
Recruiting
Site 858
Koszalin
Poland
Not Yet Recruiting
Site 852
Krakow
Poland
Not Yet Recruiting
Site 857
Mysłowice
Poland
Not Yet Recruiting
Site 859
Przemyśl
Poland
Not Yet Recruiting
Site 855
Warsaw
Poland
Not Yet Recruiting
Site 850
Wroclaw
Poland
Not Yet Recruiting
802 Institutul Regional de Gastroenterologie si Hepatologie
Cluj-Napoca
Romania
Recruiting
807 IOCN, Medical Oncology
Cluj-Napoca
Romania
Not Yet Recruiting
809 Spitalul Clinic Judetean de Urgenta Constanta Oncology Dept
Constanța
Romania
Not Yet Recruiting
801 Oncology Center "Sf. Nectarie" Medical Oncology
Craiova
Romania
Recruiting
803 Oncolab SRL
Craiova
Romania
Recruiting
805 Euroclinic lasi
Iași
Romania
Recruiting
810 IRO Iasi-Clinica Oncologie Medicala
Iași
Romania
Recruiting
808 Spitalul Clinic Pelican Oradea Oncology Department
Oradea
Romania
Recruiting
804 Oncomed - Medical Oncology
Timișoara
Romania
Recruiting
806 Oncocenter Oncologie Clinica SRL
Timișoara
Romania
Recruiting
821 Clinic for Gastroenterology and Hepatology, Military Medical Academy
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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