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The study was terminated because the originally planned VIC-1911 dose-escalation scheme (100 mg, 150 mg, 200 mg BID) was scientifically unjustified, lacking prior clinical safety data to support such starting doses when combined with lenvatinib in HC
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This is a prospective clinical study aiming to test the safety and efficacy of lenvatinib in combination with Aurora kinase A inhibitor VIC-1911 in participate with lenvatinib-unresponsive or lenvatinib-resistant hepatocellular carcinoma(HCC).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lenvatinib plus VIC-1911 combination therapy | Experimental | Subjects with lenvatinib unresponsive or lenvatinib resistant hepatocellular HCC will receive Lenvatinib plus VIC-1911 combination therapy. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lenvatinib Oral Product Plus VIC1911 | Drug | Lenvatinib: 8mg/day (≤ 60Kg), oral. VIC-1911:Groups were divided: 100mg bid(DL1, dose level 1); 150mg bid(DL2); 200mg bid(DL3), oral. 50mg bid is defined as DL(-1), 250mg bid is defined as DL(+1). A Bayesian Optimal Interval design schema will be followed to establish the maximum tolerated dose (MTD) of lenvatinib plus VIC-1911 combination and RP2D of VIC-1911 in HCC patients. The study would follow the Bayesian Optimal Interval Design with level size of 2 patients. The R package "BOIN" is available from CRAN. |
| Measure | Description | Time Frame |
|---|---|---|
| Progression free survival | Length of time from the start of combination therapy to progression of disease or death | 6 months after the last subject is enrolled. |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival | Length of time from the date of first dose of combination therapy to date of death from any cause or latest follow-up | 6 months after the last subject is enrolled |
| Safety endpoint |
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Inclusion Criteria:
(1) Unlimited gender, aged 18-75 years; (2) Meets American Association for the Study of Liver Diseases (AASLD) or European Association for the Study of the Liver (EASL) clinical diagnostic criteria of hepatocellular carcinoma; (3) Barcelona Clinic Liver Cancer (BCLC) Stage C, and there is at least one measurable tumor in the liver (long diameter ≥ 1cm);(4) Lenvatinib unresponsive or lenvatinib resistant after standard treatment; (5) Child-Pugh A or scored 7 B; (6) Eastern Cooperative Oncology Group performance status score <= 1; (7) Platelet count >= 60x10^9/L, Prothrombin time prolonged <= 6 seconds.
Exclusion Criteria:
(1) Uncorrectable coagulopathy with obvious bleeding tendency; (2) Patients need long-term anticoagulant or anti platelet therapy and cannot stop the drugs; (3) Patients with unstable or active ulcer or gastrointestinal bleeding; (4) Heart disease requiring treatment or not well controlled high blood pressure; (5) Hepatic encephalopathy or refractory ascites requiring treatment; (6) There is a clear active infection; (7) Receiving radiotherapy/chemotherapy/interventional therapy for tumor within 4 weeks before the start of the study; (8) Severe insufficiency of important organs, such as severe cardiopulmonary insufficiency; (9) Other accompanying anti-tumor treatments; (10) The investigator assessed that the patient was unable or unwilling to comply with the protocol.
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| Name | Affiliation | Role |
|---|---|---|
| Qiang XIA | Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTU | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Deparment of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University | Shanghai | 200127 | China |
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| ID | Term |
|---|---|
| D008113 | Liver Neoplasms |
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
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Bayesian Optimal Interval design
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Statistically describe the proportion of adverse events after treatment for each patient
| 6 months after the last subject is enrolled |
| D008107 |
| Liver Diseases |
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |