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

November 24, 2023 updated by: Mina Alpha Limited

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

75

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MTL-CEBPA Monotherapy
MTL-CEBPA administered weekly, twice weekly or thrice weekly over 3 weeks followed by 1 week of rest defining a 28-day cycle.
Drug: MTL-CEBPA
Intravenous administration
Experimental: MTL-CEBPA & Sorafenib (combination)
MTL-CEBPA is administered weekly or twice weekly in combination with sorafenib over 3 weeks followed by 1 week of rest defining a 28-day cycle.
Drug: MTL-CEBPA
Intravenous administration
Drug: Sorafenib 200mg
Sorafenib tablets
Experimental: MTL-CEBPA & Sorafenib (sequential)
MTL-CEBPA is administered weekly or twice weekly for 2 cycles (28-day cycle) followed by 2 cycles of sorafenib
Drug: MTL-CEBPA
Intravenous administration
Drug: Sorafenib 200mg
Sorafenib tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1- Incidence of Grade 3 or 4 drug related adverse events
Time Frame: During cycle 1 (28 days) of treatment assessed over 15 months
Frequency of adverse events graded according to NCI CTCAE v5.0
During cycle 1 (28 days) of treatment assessed over 15 months
Part 2 - Change in tumour size from baseline using RECIST 1.1 and mRECIST in patients treated with MTL-CEBPA in combination with sorafenib
Time Frame: Eight weekly intervals until death assessed for 100 weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: At the end of every cycle (28 days) of treatment assessed over 15 months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mina Alpha Limited

Investigators

  • Principal Investigator: Dr Debashis Sarker, MBChB, MRCP, Guy's and St Thomas' NHS Foundation Trust and King's College London
  • Study Director: Professor Nagy Habib, FRCS, Mina Alpha Limited

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2016

Primary Completion (Estimated)

January 1, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

March 11, 2016

First Submitted That Met QC Criteria

March 21, 2016

First Posted (Estimated)

March 22, 2016

Study Record Updates

Last Update Posted (Actual)

November 27, 2023

Last Update Submitted That Met QC Criteria

November 24, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MNA-3521-011
  • 20332 (UK NIHR CRN)
  • 2015-003051-21 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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