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First-in-Human Safety and Tolerability Study of MTL-CEBPA in Patients With Advanced Liver Cancer (OUTREACH)

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2017 by Mina Alpha Limited
Sponsor:
Information provided by (Responsible Party):
Mina Alpha Limited
ClinicalTrials.gov Identifier:
NCT02716012
First received: March 11, 2016
Last updated: June 13, 2017
Last verified: June 2017
  Purpose

This is a First in Human study of a new single agent (MTL-CEBPA) in patients with advanced cancer of the liver. The study is in two parts: dose escalation followed by a dose expansion; both parts of the study will recruit advanced hepatocellular carcinoma patients with cirrhosis. All participants will be refractory to or ineligible for loco-regional therapy including surgery, radiofrequency tumour ablation, transarterial chemoembolisation or sorafenib.

MTL-CEBPA consists of a double stranded RNA formulated into a SMARTICLES® liposomal nanoparticle and is designed to activate the CEBPA gene.


Condition Intervention Phase
Hepatocellular Carcinoma Liver Cancer Drug: MTL-CEBPA Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A First-in-Human, Multi-centre, Open-label, Phase 1 Clinical Study With RNA Oligonucleotide Drug MTL-CEBPA to Investigate Its Safety and Tolerability in Patients With Advanced Liver Cancer

Resource links provided by NLM:


Further study details as provided by Mina Alpha Limited:

Primary Outcome Measures:
  • Incidence of Grade 3 or 4 drug related adverse events and clinical lab abnormalities defined as Dose Limiting Toxicities (DLTs) using NCI CTCAE v 4.03 [ Time Frame: During cycle 1 (28 days) of treatment ]

Secondary Outcome Measures:
  • Recommended Phase 2 Dose (RP2D) of MTL-CEBPA defined as the most appropriate dose to maximise a favourable risk/benefit reward for the participant population [ Time Frame: After completion of all Cycle 1 (28 days) of treatment for participant enrolled in part 1 ]
  • Total Active Pharmaceutical Ingredient (API) levels in plasma. [ Time Frame: The pharmacokinetics profile will be assessed by blood collection during Cycle 1 (28 days) of treatment ]
  • Preliminary evidence of liver function improvement [ Time Frame: Liver function will be assessed by blood collection twice weekly at every cycle (28 days) of treatment ]

Estimated Enrollment: 51
Actual Study Start Date: March 1, 2016
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MTL-CEBPA Drug: MTL-CEBPA

Intravenous administration into a vein (peripheral or central) on day 1, 8 and 15 of each 28-day cycle.

Number of Cycles: until progression or unacceptable toxicity develops.


  Eligibility

Ages Eligible for Study:   16 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed advanced HCC with a background of liver cirrhosis
  • Patients who are considered ineligible for surgery, or any other treatment, who are progressing following loco-regional therapy and/or sorafenib Patients who are naïve to sorafenib are eligible to participate to the study when investigator consider using sorafenib is not suitable for subject after evaluating the risk/ benefit or subject is reluctant to use sorafenib.
  • 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 A or B7 disease (for HCC)
  • Willing to provide archived tumor tissue (if available) and willing to undergo pre- and on-treatment tumor biopsy (if considered safe and medically feasible by the treating investigator)
  • Acceptable laboratory parameters, as demonstrated by:

    • Platelets ≥ 75 x 109/L
    • Serum albumin > 28 g/L
    • ALT and AST ≤ 5 x ULN
    • Bilirubin ≤ 50 µmol /L
    • WBC ≥ 2.0 x 109/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 (estimated using the Cockcroft & Gault, CKD-EPI formula or equivalent according to local practice at Investigator site)

Exclusion Criteria:

  • Patients who have been treated with TACE, sorafenib or chemotherapy within the last 28 days
  • Prior systemic cancer-directed treatments within 15 days or investigational drugs within the last 30 days
  • Grade > 1 prior treatment-related toxicities (excluding alopaecia) 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
  • Patients administered with serum albumin within the last 7 days prior to the first study drug injection
  • Known infection with human immunodeficiency virus (HIV)
  • Patient with central nervous system (CNS) metastasis
  • Signs and symptoms of heart failure characterised as greater than New York Heart Association (NYHA) Class I
  • Patient presenting with a prolonged corrected QT (QTc) interval defined as ≥ 450ms (males) and ≥ 460ms (females) using Fridericia's correction formula; or other clinically significant cardiac abnormalities.
  • Major surgery within the last 30 days
  • Patients with history of organ transplantation and cardiac surgery
  • Patients with sepsis, ineffective biliary drainage with or without cholangitis, obstructive jaundice or encephalopathy
  • Evidence of spontaneous bacterial peritonitis or renal failure or allergic reactions to the agent or excipient Pregnant or lactating women
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02716012

Contacts
Contact: MiNA Alpha Limited clinicaltrials@minatx.com

Locations
Singapore
National Cancer Centre Not yet recruiting
Singapore, Singapore
Principal Investigator: Dr Han Chong Toh         
National University Hospital Not yet recruiting
Singapore, Singapore
Principal Investigator: Dr Cheng Ean Chee         
Taiwan
National Taiwan University Hospital Recruiting
Taipei, Taiwan
Principal Investigator: Professor Kai-Wen Huang         
United Kingdom
University Hospitals Birmingham NHS Foundation Trust Recruiting
Birmingham, United Kingdom
Principal Investigator: Dr yuk-Ting Ma         
Cambridge University Hospitals NHS Trust Recruiting
Cambridge, United Kingdom
Principal Investigator: Dr Bristi Basu         
The Beatson West of Scotland Cancer Centre Recruiting
Glasgow, United Kingdom
Principal Investigator: Professor Jeff Evans         
Clatterbridge Cancer Centre NHS Foundation Trust Recruiting
Liverpool, United Kingdom
Principal Investigator: Professor Daniel Palmer         
Guy's and St. Thomas' NHS Foundation Trust Recruiting
London, United Kingdom
Principal Investigator: Dr Debashis Sarker         
Imperial College Healthcare NHS Trust Recruiting
London, United Kingdom
Principal Investigator: Professor Long R Jiao         
University College London Hospitals NHS Foundation Trust Recruiting
London, United Kingdom
Principal Investigator: Professor Tim Meyer         
Newcastle upon Tyne Hospitals NHS Foundation Trust Recruiting
Newcastle, United Kingdom
Principal Investigator: Professor Ruth Plummer         
Sponsors and Collaborators
Mina Alpha Limited
Investigators
Principal Investigator: Dr Debashis Sarker, MBChB, MRCP, PhD Guy's and St Thomas' NHS Foundation Trust and King's College London
Study Director: Professor Nagy Habib, MD, ChM, FRCS Mina Alpha Limited
  More Information

Additional Information:
Responsible Party: Mina Alpha Limited
ClinicalTrials.gov Identifier: NCT02716012     History of Changes
Other Study ID Numbers: MNA-3521-011
2015-003051-21 ( EudraCT Number )
20332 ( Other Identifier: UK NIHR CRN )
Study First Received: March 11, 2016
Last Updated: June 13, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Mina Alpha Limited:
Oligonucleotide
RNA
saRNA
Fibrosis
Cirrhosis

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Liver Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on September 21, 2017