Clinical Trials List
Protocol NumberMNA-3521-011
NCT Number(ClinicalTrials.gov Identfier)NCT02716012
2016-10-01 - 2024-12-31
Others
Terminated3
Suspended1
ICD-10C22.0
Liver cell carcinoma
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.
-
Trial Applicant
A2 HEALTHCARE TAIWAN CORPORATION
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Sponsor
MiNA Alpha Ltd.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Ming-Huang Chen Division of Radiation Therapy
- Pei-Chang Lee Digestive System Department
- Yi-Hsiang Huang Digestive System Department
- Chung-Pin Li Digestive System Department
- San-Chi Chen Division of Radiation Therapy
- Rheun-Chuan Lee Division of Radiology
- Yun-Cheng Hsieh Digestive System Department
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Ming-Chin Yu Division of General Surgery
- Yi-Chung Hsieh Digestive System Department
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 郭芳穎 Division of Others
- Jing-Houng Wang Digestive System Department
- 陳建宏 Digestive System Department
- 郭垣宏 Digestive System Department
- 許獻文 Division of Radiology
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Suspended
Condition/Disease
Hepatocellular Carcinoma (HCC)
Objectives
Primary objective:
To determine the safety and tolerability of weekly administration of MTLCEBPA for 3 weeks to participants with histologically advanced cancer
characterised by hepatocellular carcinoma or advanced stage cancer presenting
with secondary liver tumours derived from extra hepatic primary cancer types.
Secondary objectives:
To determine the RP2D of MTL-CEBPA
To characterise the PK of MTL-CEBPA
To characterise the PD of MTL-CEBPA notably characterisation of MTLCEBPA effect on serum albumin and bilirubin
Test Drug
MTL-CEBPA
Active Ingredient
chemically synthesised double-stranded CEBPA-51 saRNA targeting the CEBPA promoter
Dosage Form
Injection
Dosage
2.5mg/ml, 20ml/vial
Endpoints
Primary endpoint:
In Part 1, the primary endpoint will be dose limiting toxicity (DLT) defined as:
- Any drug related toxicity grade greater than or equal to 3 according to the
Common Terminology Criteria for Adverse Events (CTCAE) v4.03 with
the only exception of AST/ ALT related DLT defined as Grade 4 AST
and/ or ALT abnormal laboratory value (> 20.0 x ULN).
DLT definition above includes:
- Grade ≥ 3 nausea, vomiting or diarrhoea in spite of adequate treatment for
more than 3 days
- Decrease in the participant’s performance status ≥ 2 points compared to
baseline
- Grade ≥ 3 fatigue for more than 7 days
- Grade ≥ 3 haemoglobin, platelets or neutrophils abnormal laboratory
value, myelosuppression for more than 5 days.
- Grade ≥ 3 bilirubin abnormal laboratory value (>3.0 x ULN)
In Part 2, safety and tolerability of MTL-CEBPA will be evaluated in terms of
frequency of adverse events.
In Part 1, the primary endpoint will be dose limiting toxicity (DLT) defined as:
- Any drug related toxicity grade greater than or equal to 3 according to the
Common Terminology Criteria for Adverse Events (CTCAE) v4.03 with
the only exception of AST/ ALT related DLT defined as Grade 4 AST
and/ or ALT abnormal laboratory value (> 20.0 x ULN).
DLT definition above includes:
- Grade ≥ 3 nausea, vomiting or diarrhoea in spite of adequate treatment for
more than 3 days
- Decrease in the participant’s performance status ≥ 2 points compared to
baseline
- Grade ≥ 3 fatigue for more than 7 days
- Grade ≥ 3 haemoglobin, platelets or neutrophils abnormal laboratory
value, myelosuppression for more than 5 days.
- Grade ≥ 3 bilirubin abnormal laboratory value (>3.0 x ULN)
In Part 2, safety and tolerability of MTL-CEBPA will be evaluated in terms of
frequency of adverse events.
Inclution Criteria
Patients with advanced stage HCC or patients with advanced tumour disease with
secondary liver tumours derived from extra hepatic primary cancer types will be
recruited to Part 1; patients with advanced HCC only will be recruited to Part 2.
For HCC patients the following applies:
Histologically confirmed advanced HCC
Patients who are considered ineligible for surgery, or any other treatment,
who are progressing following loco-regional therapy and/or sorafenib
(naïve sorafenib patients are eligible)
At least one measurable liver lesion with target lesion size ≥ 1.0 cm as
measured by MRI or CT
Child-Pugh A or B7 disease
Platelets ≥ 75 x 109
/L
Serum albumin > 28 g/L for patients with cirrhosis only (no upper or
lower limit for non-cirrhotic HCC patients)
ALT and AST ≤ 5 x ULN
For patients with secondary liver tumours the following applies:
Histologically-confirmed advanced extra-hepatic solid tumour and
incurable tumours refractory to prior standard therapies or for whom no
standard therapy exists
At least one measurable liver lesion with target lesion size ≥ 1.0 cm as
measured by MRI or CT located in the liver
Platelets ≥ 100 x 109/L
ALT and AST ≤ 3 x ULN
Other inclusion criteria
Written informed consent obtained prior to any trial specific procedure
Male or female ≥ 20 years
ECOG performance status 0 or 1
Bilirubin ≤ 50 µmol /L
WBCs ≥ 2.0 x 109
/L
Absolute neutrophil count ≥ 1.5 x 109
/L
Haemoglobin ≥ 9.0 g/dL
Prothrombin time (PT) < 20 seconds
Serum creatinine ≤ 1.5 x ULN
Calculated creatinine clearance ≥ 60 mL/min/1.73 m2 (Cockcroft & Gault,
CKD-EPI formula or equivalent according to local practice at Investigator
site)
Negative blood pregnancy test for women who could become pregnant
(within 10 days prior to first drug administration)
Safe contraception in females who could become pregnant during the entire
study, using an established treatment with hormonal contraceptives for at least
2 months prior to start of screening as detailed in the protocol. Male
participants with partners who could become pregnant are requested to use
barrier contraception in addition to having their partner use another method of
contraception during the trial and for 3 months after the last dose.
Able to comply with all the requirements of the protocol
secondary liver tumours derived from extra hepatic primary cancer types will be
recruited to Part 1; patients with advanced HCC only will be recruited to Part 2.
For HCC patients the following applies:
Histologically confirmed advanced HCC
Patients who are considered ineligible for surgery, or any other treatment,
who are progressing following loco-regional therapy and/or sorafenib
(naïve sorafenib patients are eligible)
At least one measurable liver lesion with target lesion size ≥ 1.0 cm as
measured by MRI or CT
Child-Pugh A or B7 disease
Platelets ≥ 75 x 109
/L
Serum albumin > 28 g/L for patients with cirrhosis only (no upper or
lower limit for non-cirrhotic HCC patients)
ALT and AST ≤ 5 x ULN
For patients with secondary liver tumours the following applies:
Histologically-confirmed advanced extra-hepatic solid tumour and
incurable tumours refractory to prior standard therapies or for whom no
standard therapy exists
At least one measurable liver lesion with target lesion size ≥ 1.0 cm as
measured by MRI or CT located in the liver
Platelets ≥ 100 x 109/L
ALT and AST ≤ 3 x ULN
Other inclusion criteria
Written informed consent obtained prior to any trial specific procedure
Male or female ≥ 20 years
ECOG performance status 0 or 1
Bilirubin ≤ 50 µmol /L
WBCs ≥ 2.0 x 109
/L
Absolute neutrophil count ≥ 1.5 x 109
/L
Haemoglobin ≥ 9.0 g/dL
Prothrombin time (PT) < 20 seconds
Serum creatinine ≤ 1.5 x ULN
Calculated creatinine clearance ≥ 60 mL/min/1.73 m2 (Cockcroft & Gault,
CKD-EPI formula or equivalent according to local practice at Investigator
site)
Negative blood pregnancy test for women who could become pregnant
(within 10 days prior to first drug administration)
Safe contraception in females who could become pregnant during the entire
study, using an established treatment with hormonal contraceptives for at least
2 months prior to start of screening as detailed in the protocol. Male
participants with partners who could become pregnant are requested to use
barrier contraception in addition to having their partner use another method of
contraception during the trial and for 3 months after the last dose.
Able to comply with all the requirements of the protocol
Exclusion Criteria
Exclusion criteria for HCC
Child-Pugh classes B8, B9 or C
Patients who have been treated with TACE, sorafenib or chemotherapy within
the last 28 days
Other exclusion criteria
Prior systemic cancer-directed treatments within the last 15 days or
investigational drugs within the last 30 days
Grade > 1 prior treatment-related toxicity (excluding alopaecia) at the time of
screening
Patients with clinical 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 surgical procedures that required administration of a general
anaesthetic or epidural within the last 30 days
Patients with sepsis, obstructive jaundice or encephalopathy at screening
visit or within the last two weeks
Evidence of spontaneous bacterial peritonitis or renal failure, or allergic
reaction at screening visit or in the last two weeks
Pregnant or lactating women
Any other condition (e.g., known or suspected poor compliance, etc.) that, in
the judgment of the investigator, may affect the participant’s ability to follow
the protocol specific procedures.
Child-Pugh classes B8, B9 or C
Patients who have been treated with TACE, sorafenib or chemotherapy within
the last 28 days
Other exclusion criteria
Prior systemic cancer-directed treatments within the last 15 days or
investigational drugs within the last 30 days
Grade > 1 prior treatment-related toxicity (excluding alopaecia) at the time of
screening
Patients with clinical 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 surgical procedures that required administration of a general
anaesthetic or epidural within the last 30 days
Patients with sepsis, obstructive jaundice or encephalopathy at screening
visit or within the last two weeks
Evidence of spontaneous bacterial peritonitis or renal failure, or allergic
reaction at screening visit or in the last two weeks
Pregnant or lactating women
Any other condition (e.g., known or suspected poor compliance, etc.) that, in
the judgment of the investigator, may affect the participant’s ability to follow
the protocol specific procedures.
The Estimated Number of Participants
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Taiwan
47 participants
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Global
246 participants
