First-in-Human Safety, Tolerability and Antitumour Activity Study of MTL-CEBPA in Patients With Advanced Liver Cancer

Hepatocellular Carcinoma Clinical Trial

— OUTREACH  

Official title:

A First-in-Human, Multi-centre, Open-label, Phase 1a/b Clinical Study With RNA Oligonucleotide Drug MTL-CEBPA to Investigate Its Safety, Tolerability, and Antitumour Activity in Patients With Advanced Liver Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02716012
• Other study ID #: MNA-3521-011
• Secondary ID: 2015-003051-2120
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 1, 2016
• Est. completion date: December 31, 2024

Study information

• Verified date: November 2023
• Source: Mina Alpha Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

MNA-3521-011 study is a multi-centre, open-label, first-in-human, phase 1a/b clinical study dose/dose frequency escalation followed by a cohort expansion part. MTL-CEBPA is administered as monotherapy or in combination with sorafenib to patients with advanced hepatocellular carcinoma and cirrhosis of the liver. All participants will be considered unsuitable for liver tumour resection and/or is refractory to radiotherapy and other loco-regional therapies. MTL-CEBPA consists of a double stranded RNA formulated into a SMARTICLES® liposomal nanoparticle and is designed to activate the CEBPA gene.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 75
• Est. completion date: December 31, 2024
• Est. primary completion date: January 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed advanced HCC with cirrhosis resulting from hepatitis B, hepatitis C, alcohol-related liver disease or any other aetiology OR Histologically confirmed advanced HCC resulting from NASH with or without cirrhosis
• Patient is considered unsuitable for liver tumour resection and/or is refractory to radiotherapy and other loco-regional therapies
• At least one measurable lesion with target lesion size = 1.0 cm as measured by MRI or CT
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Child-Pugh class A or B (up to B7)
• Eligible to undergo pre and post treatment mandated biopsies
• Acceptable laboratory parameters, as demonstrated by:
• Platelets = 70 x 10^9/L
• Serum albumin > 26 g/L
• ALT and AST = 5 x ULN
• Bilirubin = 50 µmol /L
• WBC = 2.0 x 10^9/L, Absolute neutrophil count = 1.5 x 109/L
• Haemoglobin = 9.0 g/dL
• Prothrombin time (PT) <20 seconds
• Acceptable renal function as demonstrated by:
• Serum creatinine = 1.5 x ULN
• Calculated creatinine clearance = 60 mL/min

Exclusion Criteria:

• Patients who have been treated with TACE or chemotherapy within the last 28 days
• Prior investigational drugs within the last 30 days
• Grade > 1 prior treatment-related toxicities (excluding alopecia) at the time of screening
• Patients with clinically significant cancer ascites
• Any episode of bleeding from oesophageal varices or other uncontrolled bleeding within the last 3 months prior to study treatment initiation
• Patients with history of haemorrhage or gastrointestinal perforation
• Patients administered with serum albumin within the last 7 days prior to the first study drug administration
• Known infection with human immunodeficiency virus (HIV)
• Patients with central nervous system (CNS), bone or peritoneal metastasis
• Patients presenting with marked baseline prolongation of QT/QTc interval defined as repeated demonstration of a QTc interval =450 ms (males) and =460 ms (females) using Fridericia's correction formula
• Signs and symptoms of heart failure characterised as greater than the New York Heart Association (NYHA) Class I or other clinically significant cardiac abnormalities (including history of myocardial infarction) including stable abnormalities.
• Major surgery within the last 30 days prior to study treatment initiation
• Patients with history of organ transplantation or cardiac surgery
• Patients with sepsis, ineffective biliary drainage with or without cholangitis, obstructive jaundice or encephalopathy at screening visit or within the last two weeks prior to study treatment initiation, whichever earlier
• Evidence of spontaneous bacterial peritonitis or renal failure or allergic reactions to the agent or excipient at screening visit or within the last two weeks prior to study treatment initiation, whichever earlier
• Known hypersensitivity to the active sorafenib or to any of the excipients
• Occurrence of a grade 3 or higher sorafenib or lenvatinib related toxicity during any sorafenib / lenvatinib treatment received prior to study enrolment, according to toxicity criteria (NCI CTCAE v 5.0)
• Pregnant or lactating women

Related Conditions & MeSH terms

• Hepatocellular Carcinoma
• Liver Cancer
• Liver Neoplasms

Intervention

Drug:
• MTL-CEBPA
Intravenous administration
• Sorafenib 200mg
Sorafenib tablets

Locations

Country	Name	City	State
Singapore	National University Hospital	Singapore
Taiwan	National Taiwan University Hospital	Taipei
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham
United Kingdom	Cambridge University Hospitals NHS Trust	Cambridge
United Kingdom	The Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Clatterbridge Cancer Centre NHS Foundation Trust	Liverpool
United Kingdom	Guy's and St. Thomas' NHS Foundation Trust	London
United Kingdom	Imperial College Healthcare NHS Trust	London
United Kingdom	The Royal Free London NHS Foundation Trust	London
United Kingdom	University College London Hospitals NHS Foundation Trust	London
United Kingdom	Newcastle upon Tyne Hospitals NHS Foundation Trust	Newcastle

Sponsors (1)

Lead Sponsor	Collaborator
Mina Alpha Limited

Countries where clinical trial is conducted

Singapore,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1- Incidence of Grade 3 or 4 drug related adverse events	Frequency of adverse events graded according to NCI CTCAE v5.0	During cycle 1 (28 days) of treatment assessed over 15 months
Primary	Part 2 - Change in tumour size from baseline using RECIST 1.1 and mRECIST in patients treated with MTL-CEBPA in combination with sorafenib	Increase or decrease in tumour measurement using Response Evaluation Criteria in Solid Tumours (RECIST) reports	Eight weekly intervals until death assessed for 100 weeks
Secondary	Part 2 - Safety and tolerability of co-administering MTL-CEBPA with sorafenib assessed using frequency of adverse events graded according to toxicity criteria (NCI CTCAE v 5.0) and categorised by body system	Frequency of treatment-related adverse events graded according to NCI CTCAE v5.0	At the end of every cycle (28 days) of treatment assessed over 15 months

External Links

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