advanced liver cancer in association with viral infections
Conditions
Interventions
Participants will be assigned to two groups to receive MTL-CEBPA + sorafenib or
sorafenib monotherapy in a 2:1 randomisation scheme.
Stratification: ALBI (albumin-bilirubin) grade (1 vs >1) and geo
Sponsors
MiNA Alpha Limited Translation & Innovation Hub,
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Written informed consent obtained prior to any specific trial-related procedure. 2. Male or female 18 years or older. 3. Histologically confirmed advanced HCC with cirrhosis in a participant with a history of hepatitis B and/or C. Participants with past or ongoing HCV infection will be eligible for the study. Participants must have completed their treatment at least 1 month prior to starting study intervention and their HCV viral load below the limit of quantification. Participants who are HCV Ab positive but HCV RNA negative due to prior treatment or natural resolution will be eligible. Participants with past or controlled ongoing hepatitis B will be eligible as long as their HBV viral load is less than 500 IU/mL prior to first dose of study drug. Participants on active HBV therapy with viral loads under 100 IU/mL should stay on the same therapy throughout study intervention. 4. Child-Pugh classification A. 5. Unsuitable for liver tumour resection and/or refractory to loco-regional therapy. 6. Not eligible for liver transplantation. 7. Had progression or recurrence of HCC following previous treatment with atezolizumab in combination with bevacizumab. Participants with progression or recurrence of HCC on non-atezolizumab anti-PD-1/PD-L1 inhibitors and non bevacizumab anti-VEGF agent in combination or as any as single agents, and no prior treatment with atezolizumab and bevacizumab, are eligible. 8. Naïve to tyrosine kinase inhibitors, including sorafenib, regorafenib, cabozantinib, and lenvatinib. 9. Participants with BCLC stage C disease. BCLC Stage B will be allowed if not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach (Appendix B). 10. Eastern Cooperative Oncology Group performance status of 0 or 1. 11. Has the ability to swallow and retain oral medication. 12. Life expectancy greater than 3 months at time of recruitment. 13. At least one measurable liver lesion (RECIST v1.1) assessed by the investigator. 14. Platelet count >70 x109/L. 15. Serum albumin >=28g/L. 16. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.0 x 109/L. 19. Absolute neutrophil count >=1.5 x 109/L. 20. Haemoglobin >=9.0 g/dL.
Exclusion criteria
Exclusion criteria: 1. Child-Pugh classification B and C. 2. Participants without a history of hepatitis B and/or hepatitis C. 3. Participants with fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtype HCC. 4. Participants with no prior therapy who are eligible for first-line treatment with atezolizumab in combination with bevacizumab. 5. Participants who received investigational drug(s) within the last 30 days prior to study treatment initiation. 6. Participants with clinically significant ascites. 7. Any episode of bleeding from oesophageal varices or other uncontrolled bleeding including clinically meaningful epistaxis within the last 3 months prior to study treatment initiation. 8. Clinically diagnosed hepatic encephalopathy in the last 6 months unresponsive to therapy. 9. Participants with a history of gastrointestinal haemorrhage or perforation. 10. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated such metastases may participate provided they are radiologically stable for at least 4 weeks by repeat imaging performed during study screening, clinically stable and without requirement of steroid treatment for at least 28 days prior to first dose of study intervention. MRI brain scan are required for all participants with stable brain metastases at screening (CT scan will be allowed if MRI is contraindicated). 11. Participants administered with serum albumin within the last 7 days prior to the first study treatment administration. 12. Known infection with human immunodeficiency virus (HIV) with CD4+ T-cell counts =450ms (males) and >=460ms (females) using Fridericia*s correction formula. 16. Participants with a screening diastolic blood pressure >90 mm Hg. 17. Clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled arrhythmia would be permitted. 18. Major surgery within the last 30 days prior to stud
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare PFS of MTL-CEBPA in combination with sorafenib compared to sorafenib alone as determined by BICR and assessed using RECIST v1.1 guidelines. | — |
Secondary
| Measure | Time frame |
|---|---|
| To compare efficacy of MTL-CEBPA in combination with sorafenib compared to sorafenib alone as assessed by BICR for the following: Best Objective Response (BOR), Objective Response Rate (ORR), Duration of Response (DoR), Time to Response (TTR), and changes in tumour size. To compare OS of MTL-CEBPA in combination with sorafenib compared to sorafenib alone. To assess consistency in tumour-based efficacy endpoints between BICR and Investigator assessment. To evaluate the safety and tolerability profile of MTL-CEBPA when administered in combination with sorafenib and compared to sorafenib alone. To compare the health-related quality of life (HRQoL) of MTL-CEBPA in combination with sorafenib compared to sorafenib alone as assessed by EORTC-QLQ-C30 plus EORTC-QLQ-HCC18 QOL questionnaires. | — |
Countries
Netherlands
Outcome results
None listed