Hepatoma, Unresectable Hepatocellular Carcinoma (HCC)
Conditions
Keywords
unresectable hepatocellular carcinoma, HCC, Yttrium-90 Microsphere
Brief summary
The main purpose of the study is to evaluate the safety and efficacy of MDN-001 injection(Yttrium-90 Microsphere Injection)in the treatment of unresectable hepatocellular carcinoma. Other purposes of this study include assessment of the effect of treatment on overall survival, the length of time it takes for the disease to worsen, if and how the treatment affects the patient's quality of life, and if and how the cancer responds to the treatment.
Detailed description
A multicenter, open and single-arm phase I clinical study to evaluate the safety and efficacy of MDN-001 injection(Yttrium-90 Microsphere Injection) in the treatment of unresectable hepatocellular carcinoma. The study aims to recruit 40 patients over a period of 24 months.
Interventions
DRUGMDN-001 Injection(Yttrium-90 Microsphere Injection)
Yttrium-90 Microsphere Injection
Sponsors
Suzhou Mednovo Yi Medical Technology Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Volunteer to join this study and sign the informed consent form. * Age: 18\~80 years old (inclusive), regardless of gender. * Clinically diagnosed hepatocellular carcinoma or pathologically diagnosed hepatocellular carcinoma. * ECOG performance status of 1 or less * Child-Pugh score A or better B (≤7). * Patients who are assessed by researchers as currently unacceptable for surgical resection or ablation, or who refuse to undergo surgical resection or ablation. * According to mRECIST standard, in contrast-enhanced MRI or CT images, there must be at least one measurable liver target lesion with the longest diameter ≥1 cm. If there are multiple target lesions, the researcher will choose them. * According to the researcher's evaluation, the expected survival time is ≥3 months. * There is no extrahepatic metastasis, and there are no other malignant tumors besides liver cancer. * The main organs function normally and meet the following requirements: blood routine: no blood transfusion or colony stimulating factor (G-CSF) treatment within 14 days before signing the informed consent form, and hemoglobin ≥ 80g/L; Platelet count \> 50× 109/L; Neutrophil count (ANC) ≥ 1.5× 109/L. Liver function: serum total bilirubin (TBIL)≤2 times the upper limit of normal value (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤5.0 times ULN；; Alkaline phosphatase (ALP)≤2.5 times ULN；; Albumin \> 30 g/L. Renal function: creatinine (Cr)≤1.5 times ULN；; Creatinine clearance rate ≥50 mL/min (calculated according to Cockcroft-Gault formula). Coagulation function: INR, PT and APTT)≤1.5 times ULN. If the subjects take warfarin or heparin for anticoagulant therapy, it is necessary to ensure that they meet the requirements of the protocol when they stop taking the drug or not. Cardiovascular function: echocardiography: LVEF (left ventricular ejection fraction) ≥50%. * According to the standard of CTCAE5.0, all the adverse events of previous systemic anti-tumor therapy were restored to baseline or ≤1 grade \[except: the neuropathy induced by previous anti-tumor therapy was stable (≤2 grade); Hair loss, fatigue, etc., which are judged by the researchers based on the actual clinical situation, cannot be restored to ≤1 level and will be in a stable state for a long time; Stable hypothyroidism after hormone replacement therapy\]. * Women and men of childbearing age must agree to take strict and effective contraceptive measures after signing informed consent, during the study period and within 6 months after the end of the experiment; Men are forbidden to donate sperm during this period, and the pregnancy test results of female subjects of childbearing age during the screening period and within 24 hours before administration must be negative.
Exclusion criteria
Participants who meet any of the following criteria are not allowed to participate in this study: * Severe liver dysfunction: including severe jaundice, hepatic encephalopathy, refractory ascites or hepatorenal syndrome. * Patients who are suitable for surgical resection or ablation after evaluation by researchers: 1) patients who are suitable for surgical resection include but are not limited to the following situations: a) patients with good liver reserve function in CNLC Ia\~IIa stage; B) If the tumor is confined to the same hepatic segment or ipsilateral hemihepatis, after MDT discussion, the patients with CNLC IIb stage who may get better effect by surgical resection than other treatments; 2) Suitable for ablation treatment includes but is not limited to the following situations: A)CNLC Ia patients; B) patients with CNLC Ib stage and Child-Pugh score of liver function grade A or better grade B (≤7). * The liver area has received external radiotherapy before. * Severe pulmonary insufficiency (FEV1/FVC\&1t; 50% or FEV1\&1t: 50% expected value or maximum ventilation per minute \< 50 L/min), patients with obvious chronic obstructive pulmonary disease or interstitial pneumonia. * Arterial perfusion imaging of technetium \[99mTc\] polymerized albumin (99mTc-MAA) showed that the percentage of hepatopulmonary shunt was more than 20%, or the absorbed dose of single lung radiation was more than 30 Gy, or the accumulated absorbed dose of lung radiation was more than 50 Gy. * Hepatic arteriography and 99mTc-MAA hepatic artery perfusion imaging showed gastrointestinal shunts, which may not be corrected by vascular interventional techniques. * Can't intubate hepatic artery, such as vascular malformation, allergic to contrast agent, allergic to anesthetic, etc. * There is a tumor thrombus in the main portal vein. * The last anti-tumor treatment (surgery, chemotherapy, immunotherapy, targeted therapy, etc.) is less than 4 weeks before the administration of the experimental drug. * Participation in other clinical studies within 4 weeks before the first administration of the study drug. * It is expected that any other forms of anti-tumor therapy will be needed during the study. * Those who have been vaccinated with live attenuated vaccine within 28 days before the administration of the first study drug or plan to be vaccinated within 60 days after the treatment of the study drug. * People with previous history of epilepsy. * Patients who have undergone major organ surgery (excluding puncture biopsy) or had significant trauma within 4 weeks before the first use of the study drug, or need to undergo elective surgery during the trial. * Patients who have undergone bone marrow transplantation or solid organ transplantation in the past. * Untreated or being treated tuberculosis patients, including but not limited to tuberculosis; Those who have been treated with standardized anti-tuberculosis treatment and confirmed to have been cured by researchers can be included. * Patients with active infection of grade ≥2 who need systemic treatment of antibiotics within 2 weeks before the administration of the study drug. * Patients who have been diagnosed with immunodeficiency disease and/or who have tested positive for human immunodeficiency virus (HIV) at the time of screening. * Patients with clinically significant cardiovascular and cerebrovascular diseases within 6 months before the first administration of the study drug, including but not limited to: acute myocardial infarction; Severe/unstable angina pectoris; History of arterial thromboembolism, including but not limited to cerebrovascular accidents; Congestive heart failure \[new york Heart Association (NYHA) \> Grade II; Any clinically significant resting ECG rhythm, abnormal conduction or morphology, complete left bundle branch block, degree III cardiac block, degree II cardiac block, and PR interval \> 250 ms；; The average corrected QT interval (QTCF) obtained by three ECG examinations is \> 450 msec (C male) or \> 470 msec (female) (only when the first ECG prompts QTCF to be \> 450 msec (male) or \> 470 msec (female), it is necessary to retest and take the average corrected value for three times (corrected according to Fridericia formula); Hypertension beyond the control of antihypertensive drugs (systolic blood pressure \> 160 mmHg and/or diastolic blood pressure \> 100 mmHg). Other cardiovascular and cerebrovascular diseases that researchers think are not suitable for selection. * Have a history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonia requiring steroid treatment, or any evidence of clinically active ILD. * Patients with mental illness that is known to interfere with trial compliance or still need drug control. * Pregnant or lactating female patients. * Any patient with severe, acute or chronic medical or mental illness or laboratory abnormality who may increase the risk of participating in the study or using the study drugs or may interfere with the interpretation of the study results and who the researcher thinks will not be suitable for participating in the study. * According to the investigator's judgment, any other circumstances that prevent the patient from participating in the clinical trial (for safety reasons) or hinder the compliance of the clinical trial procedure (for example, difficulty in venous blood collection).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Type, frequency, and severity of adverse events (AEs), serious adverse events (SAEs), treatment-emergent adverse events (TEAEs), and treatment-related adverse events (TRAEs) | 12 months | Record the types, frequencies and severity of AEs, SAEs, TEAEs and TRAEs, and grade them according to CTCAE v5.0. |
| Objective remission rate（IRC） | 6 months | The objective remission rate of liver target lesions evaluated by independent review committee (IRC) 6 months after administration of MDN-001 injection. |
| Blood biochemistry (including ALT, AST, ALP, Cr and CCr) | 12 months | — |
| CBC (including WBC, RBC and Hb) | 12 months | — |
| Urinalysis (including BLD, BIL and PRO) | 12 months | — |
| Coagulation function (including PT andAPTT) | 12 months | — |
| Cardiac enzyme panel (including CK, CK-MB and cTn) | 12 months | — |
| Stool examination and OB | 12 months | — |
| 12-lead ECG | 12 months | OT interval (milliseconds), Rate (times per minute) |
| Vital signs | 12 months | Body temperature (℃), Pulse/Heart rate (beats per minute, bpm) |
| Weight and Height | 12 months | Weight in kilograms and height in meters |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective remission rate | 12 months | (According to mRECIST and RECIST v1. 1 standards)Objective remission rate of liver target lesions assessed by researchers. |
| Time to disease progression | 12 months | (According to mRECIST and RECIST v1. 1 standards)The time from liver target lesion to disease progression evaluated by researchers and IRC |
| Tumor Response Rate | 12 months | (According to mRECIST and RECIST v1. 1 standards)The duration of remission (DOR), disease control rate (DCR) and complete remission rate (CRR) are evaluated by the researchers and IRC. |
| Progressively free survival | 12 months | — |
| Overall survival | 12 months | — |
| Changes of tumor marker alpha-fetoprotein before and after administration | 12 months | — |
| Actual distribution of yttrium-90 | 24 hours | Actual distribution of yttrium -90 in human body within 24 hours after administration. |
| Radioactivity of Yttrium-90 in blood, urine and feces of Participants | 14 days | Radioactivity of Yttrium -90 in blood, urine and feces of subjects after administration. |
| Absorbed dose and effective dose of internal irradiation after administration | 24 hours | Absorbed dose and effective dose of internal irradiation after administration: The tumor/normal liver uptake ratio (T/N ratio) and liver shunt fraction (LSF) were calculated according to SPECT/CT or PET/CT data. |
Countries
China
Contacts
CONTACTHongzhang Zhang
Outcome results
None listed