Phase II Study of Concurrent Lenvatinib and Radiotherapy for Advanced HCC

Study Overview
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Brief Summary
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This is a single-arm, open-label study performed at our hospital, patients with progression hepatocellular carcinoma (HCC) met inclusion criteria will be enrolled. Patients received oral lenvatinib 12mg/day (for patients≥60 kg) or 8 mg/day (for patients<60kg ) before local radiotherapy 8 weeks, large lesions were treated with IMRT for 40-60gy / 20-30f. Combined therapy will be taken until unacceptable treatment-related toxicities occurred or disease progression.

Official Title
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Phase II Study of Concurrent Lenvatinib and Intensity-modulated Radiotherapy (IMRT) for Advanced Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma, Radiotherapy, Lenvatinib

Intervention / Treatment
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* Radiation: concurrent lenvatinib and Radiotherapy, followed lenvatinib maintenance


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients had an HCC diagnosis confirmed either histologically or clinically according to the Chinese Society of Clinical Oncology guidelines for primary liver cancer 2019 version； Aged ≥18 years and <80 years； ECOG 0-1; Live-GTV volume > 700ml; BCLC stage C, HCC with portal vein or hepatic vein tumor thrombosis or lymph node involved (LN involved can be included one treatment planning); Estimated life expectancy should be more than 3 months; Patients with lung and / or bone metastases can be enrolled if those metastases couldn't effect the patients' life and quality of life within 3 months; Child-Pugh Score A5,A6,B7; Liver function: ALT is less than 1.5 times of the upper limit of normal; ALT is less than 0.5 times of the upper limit of normal, AST can be less than 6 times of the upper limit of normal, excluding the elevation of AST caused by heart infarction; ALT is 0.5 to 1.5 times of the upper limit of normal, AST is less than 1.5 times of the upper limit of normal; ECG examination showed no obvious abnormality, no obvious cardiac dysfunction; Renal function: CRE and BUN were within 1.5 times of the upper limit of normal value; Blood routine: HB ≥ 80g / L, ANC ≥ 1.0 × 109 / L, PLT ≥ 40 × 109 / L; Coagulation function: no bleeding tendency; Informed and voluntarily participated in the study and signed informed consent. Exclusion Criteria: Currently in the process of other clinical trials within recently four weeks; Previous abdominal radiotherapy and liver transplantation; Patients with severe chronic diseases of heart, kidney, liver and other important organs; Pregnant or lactating women; Suspected or indeed drug abusers, drug abusers and alcoholics; Allergic to lenvatinib or other treatments. Severe mental or nervous system disorders affecting informed consent and / or expression or observation of adverse reaction

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lenvatinib and IMRT<br>Concurrent Lenvatinib and IMRT, followed Lenvatinib maintenance for advanced hepatocellular carcinoma with portal vein or hepatic vein tumor thrombosis or lymph node involved | Radiation: concurrent lenvatinib and Radiotherapy, followed lenvatinib maintenance<br>* Radiotherapy with IMRT or VMAT with 40-60Gy/20-30f; Concurrent Lenvatinib 12mg/day (for patients≥60 kg) or 8 mg/day (for patients<60kg ) qd po. (Note: Levatinib can be given to patients in four weeks before Radiotherapy is applied, so that it can control disease during waiting for Radiotherapy). Maintenance Lenvatinib 12mg/day (for patients≥60 kg) or 8 mg/day (for patients<60kg ) qd po until disease progress or unacceptable adverse events; six months is recommended but not mandatory.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MST | Median Survival Time (MST) was defined as the duration from the date of patient recruited to the date of death from any cause | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Overall Response Rate (ORR) was defined as the total of CR (Complete Response) and PR (Partial Response). CR and PR were assessed by independent reviewers according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. ORR evaluated in 1 to 3 months after the completion of radiotherapy. | Assessment in 1 to 3 months after radiotherapy | 
| TTP | Time to Progression (TTP) was defined as the duration from the date of patient recruited to the first progress at any site or the date of death | 24 months | 
| Rate of III-IV grade adverse events | Adverse events was evaluated during received protocol therapy according to CTCAE 4.03 | up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatocellular carcinoma, intensity-modulated radiotherapy, portal vein thrombosis, lymph node metastasis, Lenvatinib