Toripalimab in Combination With Lenvatinib and TACE for Conversion Therapy in Patients With Potentially Resectable HCC
Efficacy and Safety of Toripalimab in Combination With Lenvatinib and TACE for Conversion Therapy in Patients With Potentially Resectable Hepatocellular Carcinoma: a Prospective, Multicenter, Randomized Controlled Study
調査の概要
詳細な説明
The study includes two groups:
Treatment group: patients with potentially resectable HCC who meet the study inclusion criteria will be treated with lenvatinib in combination with toripalimab and TACE (on demand). Tumor response will be regularly evaluated, data will be collected, and complete surgical resection will be evaluated by an independent review committee, the conversion resection rate will be calculated, and patient survival will be assessed.
Control group: patients with potentially resectable HCC who meet the study inclusion criteria will be treated with TACE. Tumor response will be regularly evaluated, data will be collected, and complete surgical resection will be evaluated by an independent review committee, the translational resection rate will be calculated, and patient survival will be assessed.
The maximum duration of study treatment for each subject is expected to be 48 weeks, with efficacy evaluation by the MDT after 2 TACE treatments to determine whether subjects meet the surgical criteria.
This study is a multicenter, randomized controlled study. The primary endpoint is the objective response rate (ORR). Historical data showed that the objective response rate of patients in the TACE group was about 40%. The objective response rate of lenvatinib in combination with toripalimab and TACE is expected to reach 60%. Using a two-sided Z test of pooled variance, α is set to 0.05, power is set to 0.8, and patients will be assigned at a 1:1 ratio. The required sample sizes are 98 (treatment group) and 98 (control group), and a total of 220 subjects are planned to be prospectively observed, taking into account a dropout rate of 10%.
研究の種類
入学 (予想される)
段階
- フェーズ 3
連絡先と場所
研究場所
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-
Shanghai
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Shanghai、Shanghai、中国、200000
- Fudan University Zhongshan Hospital
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-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Male or female patients of 18-75 years old;
- Clinical or histopathological diagnosis of hepatocellular carcinoma;
- ECOG PS score of 0-1, Child-Pugh grade A;
- Chinese stage IIb/IIIa (equal to BCLC B/C) patients with portal vein tumor thrombus (according to the Japanese PVTT grading criteria Vp3-Vp4) or more than 3 tumor nodules, without extrahepatic metastasis;
- According to the evaluation by the site multi-disciplinary team (MDT), surgical resection is not the current preferred treatment;
- No previous systemic treatment for hepatocellular carcinoma; no previous use of PD-1 inhibitor, PD-L1 inhibitor, lenvatinib or sorafenib;
- Previous TACE treatment for 0-2 times
- The patients in the treatment group voluntarily and have decided to receive treatment of lenvatinib in combination with toripalimab and TACE, and sign an informed consent form. Additional identification of qualified subjects: subjects who have received at least one combination medication enter the safety evaluation; subjects who have received at least one imaging evaluation after treatment enter the efficacy evaluation. The patients in the control group treated with TACE alone have at least one imaging evaluation.
- Patients with HBV infection (characterized by hepatitis B surface antigen [HBsAg] positive and/or hepatitis B core antibody [anti-HBcAb], with detectable HBV DNA [>10 IU/mL]) should be treated with antiviral therapy according to clinical routine, so as to ensure adequate viral suppression (HBV DNA≤2000 IU/mL or 104) before enrollment. Patients must maintain antiviral therapy during the study period and within 6 months after the last study drug administration; patients with positive hepatitis B core antibody (HBc) and undetectable HBV DNA (<10 IU/mL) will be not required to receive antiviral therapy before enrollment; these patients will be checked every cycle to monitor HBV DNA levels; if HBV DNA is detected (> 10 IU/mL), antiviral therapy will be initiated; patients with detectable HBV DNA must continue to receive antiviral therapy during the study
Exclusion Criteria:
- Clinical or pathological diagnosis of mixed liver cancer, fibrolamellar hepatocellular carcinoma or other non-hepatocellular malignant tumor components;
- Hematological examination: PLT<50×109/L, WBC<3.0×109/L or not meet the requirements of TACE treatment;
- Coagulation function: international normalized (prothrombin time) ratio (INR) > 1.2;
- Liver function indicators: serum albumin (ALB) < 2.8 g/dl, serum total bilirubin (TBIL) > 1.5 times the upper limit of normal (excluding those with biliary obstruction), serum transaminase (ALT and AST) > 3 times the upper limit of normal;
- Renal function indicators: serum creatinine (CR) > 1.5 times the upper limit of normal;
- Uncontrollable hypertension (defined as diastolic blood pressure > 90 mmHg or systolic blood pressure > 150 mmHg);
- Patients with bile duct tumor thrombi, superior mesenteric vein tumor thrombi and diffuse portal vein tumor thrombi;
- Participated in other clinical trials 30 days before screening;
- Accompanied by hepatic encephalopathy, Gilbert syndrome, sclerosing cholangitis, etc.;
- Acute gastrointestinal bleeding recorded within the last 3 months;
- Have a history of allogeneic transplantation (such as liver transplantation);
- Patients with acute or chronic active hepatitis B or C infection, hepatitis B virus (HBV) DNA > 2000IU/ml or 104 copies/ml; hepatitis C virus (HCV) RNA > 103 copies/ml; those who are positive for both hepatitis B surface antigen (HbsAg) and anti-HCV antibodies.
- Patients who have autoimmune diseases or a history of autoimmune diseases or syndromes requiring systemic use of steroids / immunosuppressants, including hypophysitis, pneumonia, colitis, hepatitis, nephritis, hyperthyroidism, hypothyroidism etc.
- Be suspected of being allergic to study drugs;
- Patients with other organ dysfunction who are expected to be unable to tolerate general anesthesia or hepatectomy;
- Other conditions in which the investigators deem the patients unsuitable for the clinical trial
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
---|---|
実験的:Treatment group
Patients with potentially resectable HCC who meet the study inclusion criteria will be treated with lenvatinib(8mg/d for BW<60kg and 12mg for BW≥60kg) in combination with toripalimab(240mg iv Q3W) and TACE (on demand).
Tumor response will be regularly evaluated, data will be collected, and complete surgical resection will be evaluated by an independent review committee, the conversion resection rate will be calculated, and patient survival will be assessed.
|
patients will be treated with lenvatinib in combination with toripalimab and TACE (on demand)
patients will be treated with lenvatinib in combination with toripalimab and TACE (on demand)
Hepatic arterial chemoembolization
|
アクティブコンパレータ:Control group
Patients with potentially resectable HCC who meet the study inclusion criteria will be treated with TACE alone.
Tumor response will be regularly evaluated, data will be collected, and complete surgical resection will be evaluated by an independent review committee, the translational resection rate will be calculated, and patient survival will be assessed.
|
Hepatic arterial chemoembolization
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Tumor response: Objective response rate (assessed based on mRECIST criteria)
時間枠:Up to approximately 36 months
|
Proportion of patients who achieve pre-defined tumor volume reduction and can maintain the minimum time limit, as the sum of complete response (CR) and partial response (PR) ratios (assessed based on mRECIST criteria)
|
Up to approximately 36 months
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Tumor response: Objective response rate (assessed based on RECIST1.1 criteria)
時間枠:Up to approximately 36 months
|
Proportion of patients who achieve pre-defined tumor volume reduction and can maintain the minimum time limit, as the sum of complete response (CR) and partial response (PR) ratios (assessed based on RECIST1.1 criteria)
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Up to approximately 36 months
|
Overall survival (OS)
時間枠:Up to approximately 36 months
|
Time period from the patient's enrollment to death due to any cause.
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Up to approximately 36 months
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Progression-free survival (PFS)
時間枠:Up to approximately 36 months
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Time period from the patient's enrollment to the event of tumor progression or death.
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Up to approximately 36 months
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Percentage of patients who can receive resection.
時間枠:Up to approximately 36 months
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Percentage of patients who can receive resection.
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Up to approximately 36 months
|
Adverse Events as assessed by CTCAE 5.0 criteria
時間枠:Up to approximately 36 months
|
the main evaluation includes surgery-related adverse events, adverse events (AE), Serious adverse events (SAE), vital signs, physical examination, and laboratory examination.
The severity of adverse events will be evaluated according to the NCI CTCAE 5.0 criteria.
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Up to approximately 36 months
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協力者と研究者
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (予想される)
研究の完了 (予想される)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- B2021-338(2)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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