MTL-CEBPA + Sorafenib for Liver Cancer

(OUTREACH2 Trial)

No longer recruiting at 1 trial location

Overseen By Nagy Habib, ChM

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mina Alpha Limited

Must be taking: Active HBV therapy

Must not be taking: Investigational drugs, Live vaccines

Disqualifiers: Child-Pugh B/C, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: Up to 100 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with advanced liver cancer linked to past hepatitis B or C infections. Participants will receive either a combination of an experimental drug, MTL-CEBPA, and a standard medicine, sorafenib (also known as Nexavar), or sorafenib alone. The researchers aim to determine if the new combination is more effective and safe. This trial suits those who have experienced liver cancer progression after previous treatments and are not eligible for surgery or a liver transplant. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on active hepatitis B therapy with viral loads under 100 IU/mL, you should continue the same therapy throughout the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of MTL-CEBPA and sorafenib is generally well tolerated by patients. Earlier studies found that this combination had an acceptable safety profile. Some patients experienced side effects related to the treatment, but these were not linked to the amount of MTL-CEBPA received, indicating that increasing the dose did not worsen the side effects.

Sorafenib, already approved for treating liver cancer, has demonstrated general safety when used as directed. Overall, the combination treatment has shown positive safety results so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about MTL-CEBPA combined with sorafenib for liver cancer because it offers a fresh approach to treatment. While sorafenib is already a standard therapy that works by blocking tumor growth, MTL-CEBPA is designed to enhance the immune response against cancer by targeting and reducing a specific protein that typically suppresses the immune system. This combination aims to boost the effectiveness of sorafenib, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for liver cancer?

This trial will compare the combination of MTL-CEBPA with sorafenib to sorafenib alone for advanced liver cancer. Research has shown that combining MTL-CEBPA with sorafenib might improve treatment outcomes. MTL-CEBPA could enhance tumor responsiveness to current cancer drugs. Earlier studies found MTL-CEBPA to be safe and effective when used with drugs like sorafenib in liver cancer models. Sorafenib is already a standard treatment for liver cancer, but using it with MTL-CEBPA might lead to better results. Early evidence suggests that adding MTL-CEBPA could enhance the fight against cancer. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced liver cancer due to hepatitis B/C, who have a life expectancy of over 3 months and are not suitable for surgery or liver transplant. They should be new to tyrosine kinase inhibitors like sorafenib and must have normal organ function tests. Pregnant women, those with severe liver impairment (Child-Pugh B/C), recent serious cardiovascular issues, other active cancers, or known allergies to the drugs tested cannot participate.

Inclusion Criteria

White Blood Cell (WBC) ≥2.0 x 109/L

At least one measurable liver lesion (RECIST v1.1) assessed by the investigator

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

Participants with a screening diastolic blood pressure >90 mm Hg

Participants who received investigational drug(s) within the last 30 days prior to study treatment initiation

I have not had sepsis, issues with bile drainage, jaundice, or brain function problems recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive MTL-CEBPA and sorafenib or sorafenib alone in 3-week cycles until disease progression or unacceptable toxicity

Up to 100 weeks

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Long-term follow-up

Participants' overall survival and progression-free survival are monitored

Approximately 1 year

What Are the Treatments Tested in This Trial?

Interventions

• MTL-CEBPA
• Sorafenib

Trial Overview The study compares two approaches: one group receives MTL-CEBPA via IV every three weeks plus oral Sorafenib starting Day 8; the other gets only Sorafenib from Day 1. The goal is to see if adding MTL-CEBPA improves outcomes in hepatocellular carcinoma patients who've had hepatitis B/C.

How Is the Trial Designed?

Group I: MTL-CEBPA in combination with sorafenib Experimental Treatment 2 Interventions

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

Group II: Sorafenib alone Active Control 1 Intervention

Oral sorafenib 400mg twice a day commencing Day1

Who Is Running the Clinical Trial?

Mina Alpha Limited

Lead Sponsor

Trials

3

Recruited

130+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04710641

Radomised Phase II Study of MTL-CEBPA Plus Sorafenib ... This is a Phase II study in patients with advanced liver cancer (hepatocellular carcinoma) as a result of hepatitis B and/or C infection.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32357963/

MTL-CEBPA, a Small Activating RNA Therapeutic ... MTL-CEBPA is the first saRNA in clinical trials and demonstrates an acceptable safety profile and potential synergistic efficacy with TKIs in HCC.

3. ddw-online.com ddw-online.com/first-patient-dosed-in-advanced-liver-cancer-clinical-trial-15629-202202/

First patient dosed in advanced liver cancer clinical trial MTL-CEBPA has demonstrated its potential to make tumours more susceptible to established anti-cancer therapies, which can significantly improve ...

4. minatx.com minatx.com/wp-content/uploads/2019/03/20190402-AACR-poster_CEBPAsorafenib-combination.pdf

20190402 AACR poster_CEBPA+sorafenib combination Here we demonstrate the outcome of MTL-CEBPA and Sorafenib combination treatment in DEN induced cirrhotic HCC rats (male. Wistar rats) exposed to DEN for 6 ...

5. sigma.larvol.com sigma.larvol.com/company.php?CompanyId=680799&tab=newstrac

MiNA Therap News MTL-CEBPA is the first saRNA in clinical trials and demonstrates an acceptable safety profile and potential synergistic efficacy with TKIs in HCC. These ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.4601

Phase Ib dose escalation and cohort expansion study of ... MTL-CEBPA + sorafenib is well tolerated with an acceptable safety profile. This study has confirmed signals of objective response to the combination treatment.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02716012

Study Details | NCT02716012 | First-in-Human Safety ... MTL-CEBPA is administered as monotherapy or in combination with sorafenib to patients with advanced hepatocellular carcinoma and cirrhosis of the liver.