Lenvatinib Plus VIC-1911 in Lenvatinib-unresponsive or Lenvatinib-resistant HCC

Study Overview
=================
Brief Summary
-----------------
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).

Official Title
-----------------
Safety and Efficacy of Lenvatinib Combined With VIC-1911 in the Treatment of Lenvatinib-unresponsive or Lenvatinib-resistant Hepatocellular Carcinoma

Conditions
-----------------
Liver Cancer, Hepatocellular Carcinoma, Resistant Cancer

Intervention / Treatment
-----------------
* Drug: Lenvatinib Oral Product Plus VIC1911


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Bayesian Optimal Interval design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lenvatinib plus VIC-1911 combination therapy<br>Subjects with lenvatinib unresponsive or lenvatinib resistant hepatocellular HCC will receive Lenvatinib plus VIC-1911 combination therapy. | Drug: Lenvatinib Oral Product Plus VIC1911<br>* 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.<br>* Other names: aurora kinase A inhibitor;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | 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. | 

Secondary Outcome Measures

| Outcome Measure | 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 | Statistically describe the proportion of adverse events after treatment for each patient | 6 months after the last subject is enrolled | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Aurora A kinase inhibitor