Trial Title:
NWRD06 DNA Plasmid for HCC After Radical Resection
NCT ID:
NCT06088459
Condition:
Hepatocellular Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Conditions: Keywords:
Hepatocellular Carcinoma
Naked DNA Vaccine
GPC3
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention model description:
This study is divided into three dose groups climbed from low-dose group to high-dose
group in turn according to the 3+3 dose escalation principle.
Three dose groups were preset in this study: dose group 1 and low-dose group [a single
dose of 1mg was administered three times at week 0, 4 and 8, respectively, with
cumulative administration of 3mg]; Dose group 2, middle-dose group [single dose of 4mg,
administered 3 times at week 0, 4, 8, respectively, cumulative administration of 12mg];
Dose group 3, high-dose group [a single dose of 8mg, administered at week 0, 4 and 8, a
total of 3 times, cumulative administration of 24mg].
After the completion of treatment, the subjects shall continue to receive safety
follow-up until 28 days after the last administration.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
1mg NWRD06 administered by electroporation
Description:
DNA plasmid delivered via IM injection + electroporation using TERESA device
Arm group label:
NWRD06 by electroporation
Intervention type:
Biological
Intervention name:
4mg NWRD06 administered by electroporation
Description:
DNA plasmid delivered via IM injection + electroporation using TERESA device
Arm group label:
NWRD06 by electroporation
Intervention type:
Biological
Intervention name:
8mg NWRD06 administered by electroporation
Description:
DNA plasmid delivered via IM injection + electroporation using TERESA device
Arm group label:
NWRD06 by electroporation
Summary:
This is a dose escalation Phase 1 clinical study to evaluate the safety and
immunogenicity of Glypican3 (GPC3)-targeted DNA plasmid vaccine (NWRD06) in patients with
GPC3-positive primary hepatocellular carcinoma after radical resection.
Detailed description:
This study is divided into three dose groups:1mg, 4mg, and 8mg. Each patient will be
administered NWRD06 by electroporation in entire study period. The Maximum tolerated dose
of NWRD06 will be determined by the classical 3+3 dose escalation schedule. The number of
patients will be ranged from 9 to 18.
After the completion of treatment, the subjects shall continue to receive safety
follow-up until 28 days after the last administration.
Immunologic reactogenicity in blood samples was assessed at week 0, week 2, week 4, week
6, week 8, week 10, week 12.
Peripheral blood samples were then collected every 3 months for immunogenicity assessment
until disease progression or specific immune response became undetectable or the study
was withdrawn for various reasons or ended (whichever occurred first).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Patients had to meet all of the following inclusion criteria:
1. 18≤ age ≤60, regardless of gender;
2. Diagnosis of primary hepatocellular carcinoma (HCC) by pathohistological
examination;
3. Immunohistochemical staining that was positive for GPC3;
4. Barcelona clinic liver cancer (BCLC) stage A/B or Chinese Hepatocellular carcinoma
Stage (CNLC) Ib-IIIa;
5. Underwent radical resection of liver cancer (surgery, ablation) followed by hepatic
artery interventional therapy before the first NWRD06 administration; The interval
between radical resection and the first NWRD06 administration was less than 12
weeks, and the interval between hepatic artery interventional therapy and the first
NWRD06 administration was more than 7 days;
6. No residual intrahepatic tumor was found by imaging examination within 4 weeks
before the first NWRD06 administration; No lymph node metastasis, no extrahepatic
metastasis;
7. Patients undergoing radical resection of liver cancer should meet the intraoperative
criteria of radical resection of liver cancer:1)There was no invasion of adjacent
organs, hilar lymph nodes or distant metastasis during the operation; 2) Negative
cutting margin;
8. No Vp4 macrovascular invasion, hepatic vein or inferior vena cava macrovascular
invasion of any grade after radical resection; Notes: Patients with VP1, VP2 and VP3
macrovascular invasion diagnosed via histopathologic examination or imaging test
meet the inclusion criteria.
9. Within 1 week before the first NWRD06 administration, ECOG performance status score
was 0-1;
10. Child-Pugh score A/B (≤7) within 1 week before the first NWRD06 administration;
11. Major organ functions were normal within 1 week before the first NWRD06
administration: 1) Blood routine: Hemoglobin (Hb) ≥90 g/L; Platelet count (PLT)
≥75×109/L; 2) The liver: Total bilirubin (TB) ≤3× upper limit of normal (ULN);
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5×ULN; Plasma
albumin ≥30g/L; 3)Kidney: Serum creatinine (Scr) ≤1.5×ULN, or creatinine clearance
≥40 mL/min (serum creatinine > 1.5 x ULN);
12. The expected survival time is more than 6 months;
13. Patients with non-viral primary HCC meet the inclusion criteria. For patients with
Hepatitis B virus-related primary HCC(HBV-HCC) or Hepatitis C virus-related primary
HCC(HCV-HCC), antiviral therapies should be carried out simultaneously;
14. Within 1 week before the first NWRD06 administration, women of childbearing age must
have a negative serum pregnancy test and consent to use effective contraception
during the use of the study drug and within 6 months after the last administration
of the study drug. For men, they should be surgically sterilized or agree to use
effective contraception during study drug use and for 6 months after the last
administration of study drug.
15. Have fully understood the study and voluntarily signed the ICF, have good
communication with the investigator, and are able to complete all treatments,
examinations, and visits stipulated in the study protocol.
Exclusion Criteria:
Patients with any of the following were excluded from the study:
1. HCC recurred or metastasis before the first NWRD06 administration;
2. Before the first NWRD06 administration, the investigator judged that the patient had
not fully recovered from the toxicity and/or complications of radical resection;
3. Accompanied by hepatic encephalopathy;
4. Regular renal dialysis is required;
5. with uncontrolled pleural effusion, pericardial effusion, or moderate or more
ascites (refers to ascites that cannot be easily controlled by diuretic treatment);
6. A history of gastrointestinal bleeding, current active bleeding, or bleeding
tendency within 28 days before screening;
7. Had received systemic antitumor therapy (including chemotherapy, molecular targeted
therapy, biological immunotherapy) for liver cancer within 28 days before screening;
8. Participated in another clinical trial or was under observation in another clinical
trial within 28 days prior to screening;
9. Continuous (more than 1 week) glucocorticoid therapy (dose equivalent to prednisone
> 10 mg/ day), except hormone replacement therapy and intratracheal
administration;
10. A history of immune deficiency or autoimmune diseases (e.g., rheumatoid joint
disease, systemic lupus erythematosus, multiple sclerosis, etc.);
11. A history of allogeneic stem cell/tissue/solid organ transplantation (including bone
marrow transplantation);
12. With uncontrolled severe infection (> grade 2 NCI-CTCAE adverse events, version
5.0);
13. Patients with a history of human immunodeficiency virus (HIV) infection or carriers
of syphilis;
14. Patients with serious other organ dysfunction or cardiopulmonary diseases;
15. Epilepsy that requires treatment with medication (e.g. steroids or antiepileptic
drugs);
16. Had or currently has other malignancies (with the exception of adequately treated
and completely cured ductal carcinoma in situ of the breast, carcinoma in situ of
the cervix, basal cell carcinoma of the skin, superficial bladder tumor, or any
malignancy that was cured more than 5 years before study entry);
17. A known history of albumin allergy, or severe allergy, or allergic disease, or
allergic constitution, or severe iodine contrast allergy, meeting any of these
criteria;
18. Severe mental illness;
19. A history of drug or alcohol abuse;
20. Pregnant or lactating women, or women of childbearing age with positive blood
pregnancy tests;
21. Patients deemed by the investigator to be ineligible for this clinical trial.
Gender:
All
Minimum age:
18 Years
Maximum age:
60 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Cancer Hospital, Chinese Academy of Medical Sciences
Address:
City:
Beijing
Country:
China
Status:
Recruiting
Contact:
Last name:
Zhen Huang, M.D.
Phone:
86-010-87787100
Email:
huangzhen@cicams.ac.cn
Investigator:
Last name:
Hong Zhao, M.D.
Email:
Principal Investigator
Start date:
November 2023
Completion date:
June 2025
Lead sponsor:
Agency:
Newish Technology (Beijing) Co., Ltd.
Agency class:
Industry
Source:
Newish Technology (Beijing) Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06088459
