Radomised Phase II Study of MTL-CEBPA Plus Sorafenib or Sorafenib Alone
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.
detailed description
After a participant has signed the consent form to confirm they wish to participate in the study a number of assessments (screening) will be completed to determine whether they are suitable to be enrolled in the study. Prior to the the first dose of experimental drug (MTL-CEBPA) a 2:1 randomisation programme will allocate to which arm the person will be allocated. For participants allocated to the combination treatment arm, MTL-CEBPA will be given via infusion on the first day (Cycle 1 Day 1) of the study. It will subsequently be administered every 21 days. Sorafenib tablets (a drug which is already used to treat liver cancer) will be started on the eighth day of the study and taken daily whilst the participant is in the study. If the participant is tolerating the combination of drugs and there is no evidence that the cancer is advancing they will continue to receive cycles (21 days in length) of treatment. For participants allocated to the single treatment arm, sorafenib tablets will be started on Day 1. All participants will have contrast-enhanced CT scans of the chest, abdomen and pelvis at the beginning of the study and then every 8 weeks whilst in the study. Assessments will be completed throughout the study to ensure the combination of drugs is safe. These will include recording any adverse events (untoward medical occurrences), vital signs (such as blood pressure, pulse, body temperature, and breathing rates), ECG, and completing blood tests. Blood samples, analysed in both local (hospital/clinic site) and central laboratories (ie, facilities independent of hospital/clinic labs) will be taken throughout the study. The maximum amount of blood taken in any 28-day treatment cycle is approximately 182 mL. A patient questionnaire will be used to assess changes in health-related quality of life for participants. The questionnaire will be used for all participants in the study and will be completed every 3 weeks. All participants will be offered an optional liver tumour biopsy prior to being administered study treatment and again if clinically feasible during treatment.
official title
An Open Label, Randomised Phase 2 Study to Evaluate the Safety and Efficacy of MTL-CEBPA Administered in Combination With Sorafenib or Sorafenib Alone in TKI naïve Participants With Previously Treated Advanced Hepatocellular Carcinoma (HCC) and Hepatitis B or Hepatitis C Virus (OUTREACH2)