Cirrhosis, Hepatocellular Carcinoma
Conditions
Keywords
Hepatocellular carcinoma, HCC, Liver cancer, Child-Pugh Class B7 cirrhosis, CPB7
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.
Interventions
DRUGNamodenoson
Adenosine A3 Receptor (A3AR) agonist
DRUGPlacebo
Control arm
Sponsors
Can-Fite BioPharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Parallel group, double-blinded, randomization in a 1:1 ratio to active versus placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | From the time of randomization until the date of disease progression or death from any cause, assessed up to 60 months | Median time to disease progression using RECIST and modified RECIST criteria |
| Objective Response Rate (ORR) | Through study completion, with a median of 9 months | Proportion of patients who experience Objective Response (OR) using RECIST and modified RECIST criteria |
| Incidence and nature of treatment-emergent adverse events | Through study completion, with a median of 9 months | Incidence and nature of treatment-emergent adverse events as assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v5) |
| Pharmacokinetics (PK) of namodenoson in this population | 29 days | Plasma concentration of namodenoson |
Other
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | Through study completion, with median of 9 months | Proportion of patients who experience OR as well as those who experience Stable Disease (SD) for at least four treatment cycles, ie, four months |
| Quality of Life (QOL) using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) | Through study completion, with a median of 9 months | Assess QOL in this population using the EORTC QLQ-C30, a 30-item questionnaire. Each question is measured in a range in score from 0 to 100. A high scale score represents a higher response level. |
| Quality of Life (QOL), using the hepatocellular carcinoma- (HCC-) specific module of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Hepatocellular Carcinoma 18-question Module (EORTC QLQ-HCC18) | Through study completion, with a median of 9 months | Assess QOL in this population using the HCC-specific module of the EORTC QLQ-HCC18, an 18-item questionnaire. Each question is measured in a range in score from 0 to 100. A high scale score represents a higher response level. |
| Duration Of Response (DOR) | Through study completion, with median of 9 months | Time from first response (CR or PR) to progression or death, whichever occurs first |
Countries
Bosnia and Herzegovina, Bulgaria, Israel, Moldova, Poland, Romania, Serbia, Slovakia, United States
Contacts
Primary ContactZivit Harpaz
Outcome results
None listed