Radomised Phase II Study of MTL-CEBPA Plus Sorafenib or Sorafenib Alone

NCT04710641 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: MNA-3521-014-RNDZ
• Study Type: interventional
• Target: 8
• Locations: 2 countries
• Sites: 2

Brief Summary

This is a Phase II study in patients with advanced liver cancer (hepatocellular carcinoma) as a result of hepatitis B and/or C infection. Participants will be dosed with either MTL-CEBPA (an experimental treatment) and sorafenib or sorafenib alone. The MTL-CEBPA is administered once every 3 weeks via intravenous infusion. Sorafenib is taken orally from Day 8 for the combination group or Day 1 for the sorafenib alone group at a dose of 400 mg twice a day. Participants will receive 3 week cycles of treatment until disease progression, unacceptable toxicity, withdrawal of consent or death occurs. The combination of MTL-CEBA and sorafenib combination of treatment was tested in a previous Phase I study (OUTREACH) which showed anti-tumour activity along with a good safety and toxicity profile.

Conditions

Hepatocellular Carcinoma; Hepatitis B; Hepatitis C

Keywords

saRNA; MTL-CEBPA; Sorafenib

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  Change from baseline CT scan using blinded central review of Response Evaluation Criteria in Solid Tumours v.1.1 and compare between the two arms

  From baseline CT scan until end of documented progression or date of death from any cause assessed up o 100 weeks

Secondary Outcomes (3)

• Health-related quality of life (HRQoL) questionnaires

  From first cycle of treatment to end of study approximately one year

• Overall survival (OS)

  From first dose of MTL-CEBPA and sorafenib or sorafenib alone to end of treatment

• Adverse events

  From first dose of MTL-CEBPA and sorafenib or sorafenib alone to end of treatment

Study Arms (2)

MTL-CEBPA in combination with sorafenib

EXPERIMENTAL

Intravenous infusion of MTL-CEBPA 130mg/m2 given once every 3 weeks. Oral sorafenib 400mg twice a day will commence C1D8.

Drug: MTL-CEBPA; Drug: Sorafenib

Sorafenib alone

ACTIVE COMPARATOR

Oral sorafenib 400mg twice a day commencing Day1

Drug: Sorafenib

Interventions

MTL-CEBPA DRUG

Administered once every 3 weeks on Day 1 of each 3 week cycle.

MTL-CEBPA in combination with sorafenib

Sorafenib DRUG

Oral adminstration twice a day

Also known as: Nexavar

MTL-CEBPA in combination with sorafenib; Sorafenib alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Child-Pugh classification B and C.
• Participants without a history of hepatitis B and/or hepatitis C.
• Participants with fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtype HCC.
• Participants with no prior therapy who are eligible for first-line treatment with atezolizumab in combination with bevacizumab.
• Participants who received investigational drug(s) within the last 30 days prior to study treatment initiation.
• Participants with clinically significant ascites.
• Any episode of bleeding from oesophageal varices or other uncontrolled bleeding including clinically meaningful epistaxis within the last 3 months prior to study treatment initiation.
• Clinically diagnosed hepatic encephalopathy in the last 6 months unresponsive to therapy.
• Participants with a history of gastrointestinal haemorrhage or perforation.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated such metastases may participate provided they are radiologically stable for at least 4 weeks by repeat imaging performed during study screening, clinically stable and without requirement of steroid treatment for at least 28 days prior to first dose of study intervention. MRI brain scan are required for all participants with stable brain metastases at screening (CT scan will be allowed if MRI is contraindicated).
• Participants administered with serum albumin within the last 7 days prior to the first study treatment administration.
• Known infection with human immunodeficiency virus (HIV) with CD4+ T-cell counts \<350cells/μL or with a history of AIDS-defining opportunistic infection. No HIV testing is required unless mandated by local health authority.
• Received a live vaccine within 30 days prior to the first dose of study treatment.Live vaccines include, but are not limited to: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccinesfor injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• Known other malignancy that is progressing or has required active treatment in the last 5years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death such as early-stage cancers treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy.
• Participants presenting with a baseline prolongation of QT/QTc interval defined as repeated demonstration of a QTc interval ≥450ms (males) and ≥460ms (females) using Fridericia's correction formula.

Sponsors & Collaborators

• Mina Alpha Limited: lead

Study Sites (2)

City of Hope

Duarte, California, 91012, United States

Location

National University Hospital Singapore

Singapore, 119228, Singapore

Location

Related Links

• Sponsor website

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Hepatitis B; Hepatitis C

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Flaviviridae Infections; RNA Virus Infections

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be randomised 2:1 to receive either both the experimental drug, MTL-CEBPA, and sorafenib tablets or sorafenib tablets alone

Study Record Dates

• First Submitted: January 7, 2021
• First Posted: January 15, 2021
• Study Start: January 1, 2022
• Primary Completion: January 25, 2025
• Study Completion: January 25, 2025
• Last Updated: March 6, 2025

Record last verified: 2023-11

Locations

US (1); SG (1)