NCT02716012

Brief 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.

Trial Health

47
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
75

participants targeted

Target at P50-P75 for phase_1 hepatocellular-carcinoma

Timeline
Completed

Started Mar 2016

Longer than P75 for phase_1 hepatocellular-carcinoma

Geographic Reach
3 countries

11 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2016

Completed
10 days until next milestone

First Submitted

Initial submission to the registry

March 11, 2016

Completed
11 days until next milestone

First Posted

Study publicly available on registry

March 22, 2016

Completed
9.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2025

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2025

Completed
Last Updated

March 10, 2025

Status Verified

November 1, 2023

Enrollment Period

9.3 years

First QC Date

March 11, 2016

Last Update Submit

March 5, 2025

Conditions

Hepatocellular CarcinomaLiver Cancer

Keywords

OligonucleotideRNAsaRNASorafenibMyeloid

Outcome Measures

Primary Outcomes (2)

  • 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

  • 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 Outcomes (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

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

Study Arms (3)

MTL-CEBPA Monotherapy

EXPERIMENTAL

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

MTL-CEBPA & Sorafenib (combination)

EXPERIMENTAL

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-CEBPADrug: Sorafenib 200mg

MTL-CEBPA & Sorafenib (sequential)

EXPERIMENTAL

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

Drug: MTL-CEBPADrug: Sorafenib 200mg

Interventions

MTL-CEBPADRUG

Intravenous administration

MTL-CEBPA & Sorafenib (combination)MTL-CEBPA & Sorafenib (sequential)MTL-CEBPA Monotherapy
Sorafenib 200mgDRUG

Sorafenib tablets

MTL-CEBPA & Sorafenib (combination)MTL-CEBPA & Sorafenib (sequential)

Eligibility Criteria

Age16 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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:
  • +2 more criteria

You may not qualify if:

  • 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
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

National University Hospital

Singapore, Singapore

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, United Kingdom

Location

Cambridge University Hospitals NHS Trust

Cambridge, United Kingdom

Location

The Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom

Location

Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, United Kingdom

Location

Guy's and St. Thomas' NHS Foundation Trust

London, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, United Kingdom

Location

The Royal Free London NHS Foundation Trust

London, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, United Kingdom

Location

Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle, United Kingdom

Location

Related Publications (1)

  • 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.

    PMID: 32357963DERIVED

Related Links

MeSH Terms

Conditions

Carcinoma, HepatocellularLiver Neoplasms

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea CompoundsUreaAmidesOrganic ChemicalsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsNiacinamideNicotinic AcidsAcids, HeterocyclicHeterocyclic CompoundsPyridinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Dr Debashis Sarker, MBChB, MRCP

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

    PRINCIPAL INVESTIGATOR

  • Professor Nagy Habib, FRCS

    Mina Alpha Limited

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 11, 2016

First Posted

March 22, 2016

Study Start

March 1, 2016

Primary Completion

July 1, 2025

Study Completion

July 31, 2025

Last Updated

March 10, 2025

Record last verified: 2023-11

Data Sharing

IPD Sharing
Will not share

Locations

GB(9)SG(1)TW(1)