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Hepatocellular CarcinomaPhase 1OUTREACHNCT02716012

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

A Phase 1 study testing MTL-CEBPA and Sorafenib 200mg in people with Hepatocellular Carcinoma and Liver Cancer, run by Mina Alpha Limited at 11 sites in 3 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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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. Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
Hepatocellular Carcinoma, Liver Cancer
What is being tested?
MTL-CEBPA and Sorafenib 200mg
Could I receive a placebo?
No, everyone receives an active treatment
How many people
75 participants
Where
11 sitesin 3 countries
Study dates
1 Mar 2016to 31 Jul 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
Show all 17Show fewer
  • 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

Who cannot join

  • 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
Show all 18Show fewer
  • 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

Trial locations and contacts

11 sites in 3 countries.

11 sites in 3 countries

United Kingdom9 sites

  • University Hospitals Birmingham NHS Foundation Trust

    Birmingham

  • Cambridge University Hospitals NHS Trust

    Cambridge

  • The Beatson West of Scotland Cancer Centre

    Glasgow

  • Clatterbridge Cancer Centre NHS Foundation Trust

    Liverpool

  • Guy's and St. Thomas' NHS Foundation Trust

    London

  • Imperial College Healthcare NHS Trust

    London

  • The Royal Free London NHS Foundation Trust

    London

  • University College London Hospitals NHS Foundation Trust

    London

  • Newcastle upon Tyne Hospitals NHS Foundation Trust

    Newcastle

Other trials in United Kingdom

Singapore1 site

  • National University Hospital

    Singapore

Other trials in Singapore

Taiwan1 site

  • National Taiwan University Hospital

    Taipei

Other trials in Taiwan

About this study

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

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.

Being tested
MTL-CEBPA, Sorafenib 200mg
Keywords
Oligonucleotide, RNA, saRNA, Sorafenib, Myeloid
Medical subject headings
Carcinoma, Hepatocellular, Liver Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MTL-CEBPADrug

    Intravenous administration

  • Sorafenib 200mgDrug

    Sorafenib tablets

Study groups in NCT02716012
Study groupRoleWhat they receive
MTL-CEBPA MonotherapyExperimentalMTL-CEBPA administered weekly, twice weekly or thrice weekly over 3 weeks followed by 1 week of rest defining a 28-day cycle.
Receives: Drug: MTL-CEBPA
MTL-CEBPA & Sorafenib (combination)ExperimentalMTL-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.
Receives: Drug: MTL-CEBPA; Drug: Sorafenib 200mg
MTL-CEBPA & Sorafenib (sequential)ExperimentalMTL-CEBPA is administered weekly or twice weekly for 2 cycles (28-day cycle) followed by 2 cycles of sorafenib
Receives: Drug: MTL-CEBPA; Drug: Sorafenib 200mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1- Incidence of Grade 3 or 4 drug related adverse events

    Frequency of adverse events graded according to NCI CTCAE v5.0

    Measured: During cycle 1 (28 days) of treatment assessed over 15 months

  2. 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

    Measured: Eight weekly intervals until death assessed for 100 weeks

Secondary outcomes (1)

  1. 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

    Measured: At the end of every cycle (28 days) of treatment assessed over 15 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Mar 2016 (estimated)
  2. Study start1 Mar 2016
  3. Primary completion1 Jul 2025 (estimated)
  4. Study completion31 Jul 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
75 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02716012
Sponsor's protocol ID
MNA-3521-011
Other IDs
2015-003051-21, 20332, 2015
Acronym
OUTREACH
Status last verified
Nov 2023
First submitted
11 Mar 2016
Last updated
10 Mar 2025
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Sarker D, Plummer R, Meyer T, Sodergren MH, Basu B, Chee CE, Huang KW, Palmer DH, Ma YT, Evans TRJ, Spalding DRC, Pai M, Sharma R, Pinato DJ, Spicer J, Hunter S, Kwatra V, Nicholls JP, Collin D, Nutbrown R, Glenny H, Fairbairn S, Reebye V, Voutila J, Dorman S, Andrikakou P, Lloyd P, Felstead S, Vasara J, Habib R, Wood C, Saetrom P, Huber HE, Blakey DC, Rossi JJ, Habib N. MTL-CEBPA, a Small Activating RNA Therapeutic Upregulating C/EBP-alpha, in Patients with Advanced Liver Cancer: A First-in-Human, Multicenter, Open-Label, Phase I Trial. Clin Cancer Res. 2020 Aug 1;26(15):3936-3946. doi: 10.1158/1078-0432.CCR-20-0414. Epub 2020 May 1.

    PubMed 32357963

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MTL-CEBPA and Sorafenib 200mg in people with Hepatocellular Carcinoma and Liver Cancer, run by Mina Alpha Limited at 11 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 10 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United Kingdom, Singapore, Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02716012, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2025.

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