an open label, randomised, phase 2 study to evaluate the safety and efficacy of mtl-cebpa administered in combination with sorafenib or sorafenib alone, in TKI naïve participants with previously treated advanced hepatocellular carcinoma (HCC) and hepatitis B or hepatitis C virus (outreach2)
- Conditions
- advanced liver cancer in association with viral infections1004743810019815
- Registration Number
- NL-OMON51314
- Lead Sponsor
- MiNA Alpha Limited Translation & Innovation Hub,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 6
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) <=5 x
the upper limit of normal (ULN).
17. Bilirubin <=50 µmol /L.
18. White Blood Cell (WBC) >=2.0 x 109/L.
19. Absolute neutrophil count >=1.5 x 109/L.
20. Haemoglobin >=9.0 g/dL.
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 <350 cells/µL or with a history of AIDS-defining opportunistic
infection. No HIV testing is required unless mandated by local health authority.
13. Received a live vaccine within 30 days prior to the first dose of study
treatment. Live vaccines include, but are not limited to: measles, mumps,
rubella, varicella/zoster (chicken pox), yellow fever, rabies, BCG, and typhoid
vaccine. Seasonal influenza vaccines for injection are generally killed virus
vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®)
are live attenuated vaccines and are not allowed.
14. Known other malignancy that is progressing or has required active treatment
in the last 5 years prior to screening, with the exception of malignancies with
a negligible risk of metastasis or death such as early-stage cancers treated
with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma
of the skin, in situ cervical cancer, or in situ breast cancer that has
undergone potentially curative therapy.
15. Participants presenting with a baseline prolongation of QT/QTc interval
defined as repeated demonstration of a QTc interval >=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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To compare PFS of MTL-CEBPA in combination with sorafenib compared to sorafenib<br /><br>alone as determined by BICR and assessed using RECIST v1.1 guidelines. </p><br>
- Secondary Outcome Measures
Name Time Method <p>To compare efficacy of MTL-CEBPA in combination with sorafenib compared to<br /><br>sorafenib alone as assessed by BICR for the following: Best Objective Response<br /><br>(BOR), Objective Response Rate (ORR), Duration of Response (DoR), Time to<br /><br>Response (TTR), and changes in tumour size.<br /><br><br /><br>To compare OS of MTL-CEBPA in combination with sorafenib compared to sorafenib<br /><br>alone.<br /><br><br /><br>To assess consistency in tumour-based efficacy endpoints between BICR and<br /><br>Investigator assessment.<br /><br><br /><br>To evaluate the safety and tolerability profile of MTL-CEBPA when administered<br /><br>in combination with sorafenib and compared to sorafenib alone.<br /><br><br /><br>To compare the health-related quality of life (HRQoL) of MTL-CEBPA in<br /><br>combination with sorafenib compared to sorafenib alone as assessed by<br /><br>EORTC-QLQ-C30 plus EORTC-QLQ-HCC18 QOL questionnaires. </p><br>