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

NCT ID: NCT02716012

Last Updated: 2025-03-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

75 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-03-01

Study Completion Date

2025-07-31

Brief Summary

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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.

Detailed Description

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Conditions

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Hepatocellular Carcinoma Liver Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

MTL-CEBPA

Intervention Type DRUG

Intravenous administration

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.

Group Type EXPERIMENTAL

MTL-CEBPA

Intervention Type DRUG

Intravenous administration

Sorafenib 200mg

Intervention Type DRUG

Sorafenib tablets

MTL-CEBPA & Sorafenib (sequential)

MTL-CEBPA is administered weekly or twice weekly for 2 cycles (28-day cycle) followed by 2 cycles of sorafenib

Group Type EXPERIMENTAL

MTL-CEBPA

Intervention Type DRUG

Intravenous administration

Sorafenib 200mg

Intervention Type DRUG

Sorafenib tablets

Interventions

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MTL-CEBPA

Intravenous administration

Intervention Type DRUG

Sorafenib 200mg

Sorafenib tablets

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mina Alpha Limited

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dr Debashis Sarker, MBChB, MRCP

Role: PRINCIPAL_INVESTIGATOR

Guy's and St Thomas' NHS Foundation Trust and King's College London

Professor Nagy Habib, FRCS

Role: STUDY_DIRECTOR

Mina Alpha Limited

Locations

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National University Hospital

Singapore, , Singapore

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

University Hospitals Birmingham NHS Foundation Trust

Birmingham, , United Kingdom

Site Status

Cambridge University Hospitals NHS Trust

Cambridge, , United Kingdom

Site Status

The Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status

Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, , United Kingdom

Site Status

Guy's and St. Thomas' NHS Foundation Trust

London, , United Kingdom

Site Status

Imperial College Healthcare NHS Trust

London, , United Kingdom

Site Status

The Royal Free London NHS Foundation Trust

London, , United Kingdom

Site Status

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status

Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle, , United Kingdom

Site Status

Countries

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Singapore Taiwan United Kingdom

References

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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.

Reference Type DERIVED
PMID: 32357963 (View on PubMed)

Related Links

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http://minatx.com

Company Webpage

Other Identifiers

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2015-003051-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20332

Identifier Type: OTHER

Identifier Source: secondary_id

MNA-3521-011

Identifier Type: -

Identifier Source: org_study_id

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