Advanced hepatocellular carcinoma
Conditions
Interventions
Treated- group:Treated by CD-801 through the hepatic artery and/or intratumoral injection
Sponsors
Shanghai Changzheng Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1)Males or females, aged 18 years or older. 2)Subjects must have confirmed diagnosis of HCC with any of the following criteria according to the American Association for the Study of Liver Diseases criteria: (1)In those most at-risk patients with HBV/HCV infection or cirrhosis from any etiology, the diagnosis of HCC in lesions = 1 cm in size could be based on noninvasive imaging criteria: arterial phase hyperenhancement (APHE) and washout on portal venous or delayed phases of contrast-enhanced multiphase CT or MRI. (2)Histologically or cytologically confirmed diagnosis of HCC. 3)Unresectable HCC. 4)Subjects are not eligible for locoregional or systemic therapies, or had disease progression or would not benefit after at least one of the therapies according to any of the following criteria: (1)CT/MRI examination showed residual tumors 1 month after 2 or more ablation treatments. (2)After 2 or more TACE treatments, CT/MRI examination showed more than 50% definite viable disease, development of new HCC, new vascular invasion or extrahepatic metastases, or improvement for tumor markers lacked. (3)According to mRECIST, subjects had disease progression while receiving at least one systemic therapy , or were intolerant of systemic therapies. 5)According to mRECIST, subjects should be with at least 1 measurable target lesion meeting the following criteria: (1)The lesion could be accurately measured in at least 1 dimension as 1 cm or more. (2)The lesion is suitable for repeat measurement. (3)The lesion shows intratumoral arterial enhancement on contrast-enhanced MRI. (4)The longest diameter of the lesion for intratumoral injection should be 5.0 cm or less. Lesions previously treated with surgical resection, radiotherapy or locoregional therapy must show radiographic evidence of disease progression according to mRECIST to be deemed a target lesion . 6)Life expectancy of 12 weeks or more. 7)Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2. 8)Male with fertility and females of childbearing potential are willing to use a highly effective method of contraception for the entire study period and for 6 months after study drug discontinuation. Females of childbearing age, including premenopausal females and within 2 years after menopause, must have a negative serum pregnancy test result within 7 days prior to the first dose of study treatment. 9)Subjects who have voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.
Exclusion criteria
Exclusion criteria: 1)ALB 5.0 mg/dL, or aspartate aminotransferase (AST), alkaline phosphatase (ALP), or alanine aminotransferase (ALT) >5×ULN. 2)Inadequate renal function defined as creatinine >1.5 times the upper limit of normal (ULN) or calculated creatinine clearance 2.3. 5)Subjects with a history of liver transplantation. 6)Subjects with poorly controlled hypertension, diabetes or other serious heart or lung diseases, or with serious dysfunction. 7)Subjects with extrahepatic metastasis who have not received first-line systemic therapies (excluding those who are not eligible for systemic therapies) or who are receiving effective systemic therapy currently. 8)Subjects who had prior anticancer treatment with any locoregional therapies, antiangiogenic targeted therapies, immune checkpoint inhibitors or chemotherapy (within 4 weeks, or within 2 weeks in case of sorafenib), radiotherapy (within 3 weeks), or active traditional Chinese medicine (within 2 weeks) before the first dose of study treatment, except for the treatments after which the disease still progressed according to mRECIST. 9)All toxicities related to prior locoregional or systemic anti-tumor treatments are still grade 2 or more (except for hair loss and other events that have been judged tolerable by researchers). 10)Subjects with complication histories of liver cirrhosis or HCC such as gastrointestinal hemorrhage, overt hepatic encephalopathy, or uncontrollable ascites within 2 weeks prior to the first dose of study treatment. 11)Uncontrolled active infection (eg, lung infections, or abdominal infections). 12)Subjects with moderate to severe hepatic artery- portal vein fistula or hepatic artery - vein fistula which could not be avoided even through the artery super selection by DSA, excluding subjects who will receive intratumoral injection. 13)History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%), such as adequately treated early gastric carcinoma, carcinoma in situ of the cervix, non-melanoma skin carcinoma, or localized prostate cancer. 14)HBV DNA greater than 500 IU/mL, or HCV RNA greater than 100 IU/mL. 15)Subject is positive for Human Immunodeficiency Virus (HIV). 16)Any subject who is allergic to MRI contrast agents. 17)Pregnant/lactating women, or women who have the possibility of pregnancy. 18)Participation in other investigational drug trials within 4 weeks prior to initiation of this study treatment. 19)Any medical or other condition which, in the opinion of the investigator, would preclude participation in this clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the dose limiting toxicities and maximum tolerated dose for the treantment of CD-801 in the dose-escalation phase;To assess the objective response rate (ORR) by mRECIST and RECIST v1.1 in the dose-expansion phase; | — |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate objective response rate (ORR) by mRECIST and RECIST v1.1 in the dose-escalation phase;To evaluate duration of response, progression-free survival,time to progression,time to response,disease control rate,and clinical benefit rate by mRECIST and RECIST v1.1 in the dose-expansion phase; | — |
Countries
CHINA
Contacts
Public ContactXIE WEIFEN
Shanghai Changzheng Hospital
Outcome results
None listed