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Efficacy and Safety of Lenvatinib as a Conversion Therapy for HCC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04241523
Recruitment Status : Recruiting
First Posted : January 27, 2020
Last Update Posted : January 27, 2020
Sponsor:
Collaborators:
Tongji Hospital
Anhui Provincial Hospital
West China Hospital
Information provided by (Responsible Party):
Jian Zhou, Shanghai Zhongshan Hospital

Brief Summary:
Lenvatinib is the standard of care for patients with advanced hepatocellular carcinoma (HCC). The aim of the single-arm, open-label, phase II clinical trial is to assess efficacy and safety of lenvatinib as a preoperative conversion therapy in patients with potentially resectable HCC. Investigator hypothesized that lenvatinib may be an effective conversion treatment for HCC, and preoperative treatment with lenvatinib can improve resectability in patients with potential resectable HCC and improve the long term survival.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma (HCC) Drug: Lenvatinib 4 mg Oral Phase 2

Detailed Description:

For patients with potentially resectable HCC (intermediate or advanced stage), upfront therapy with surgical resection is of high recurrence rate after surgery. The aim of the single-arm, open-label, prospective phase II clinical trial is to evaluate whether preoperative lenvatinib treatment could improve resectability and therefore improve the long term survival.

Participants who are recruited in this study in this study will be treated with lenvatinib and will be evaluated for the feasibility for surgical resection by a multidisciplinary team every 8 weeks. If the participants underwent curative resection, they will receive lenvatinib treatment for 48 weeks after surgery.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Lenvatinib as a Conversion Therapy in Patients With Potentially Resectable Hepatocellular Carcinoma: A Single-Arm and Open-Label Prospective Study
Estimated Study Start Date : January 2020
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : February 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Lenvatinib

Arm Intervention/treatment
Experimental: Treatment
The patients will receive lenvatinib treatment and will be evaluated for the feasibility of liver resection every 8 weeks. For those who underwent liver resection, they will receive lenvatinib treatment for another 48 weeks. In case of tumor recurrence, intolerance, death, or need for other antitumor treatment, the treatment shall be stopped.
Drug: Lenvatinib 4 mg Oral

Planned doses of 8 mg of lenvatinib per day for patients with body weight <60 kg, and 12 mg for those with body weight ≥60 kg.

In case of treatment-related adverse effects, interruption or reduction is allowed.

Other Name: Lenvima 4 mg Oral




Primary Outcome Measures :
  1. Resection rate [ Time Frame: 1 year after LPI ]
    The percentage of patients who receive curative liver resection for HCC. The criteria for curative resection: (1) no active tumor thrombosis is observed in hepatic veins, portal veins, bile ducts or inferior vena cava; or the type of portal vein invasion was converted from Vp3/Vp4 to Vp1/Vp2; (2) no active metastasis to adjacent organs or distant organs, or to lymph nodes; (3) the surgical margin ≥ 0.5 cm; (4) the number of active tumor nodules decreases from ≥4 to <4; (5) the ratio of future liver volume to standard liver volume increases from <40% to ≥40% (for those with liver cirrhosis) or from <30% to ≥30% (for those without liver cirrhosis).


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: 3 years ]
    The duration from the date of recruitment to the date of death from any cause.

  2. Objective response rate (ORR) [ Time Frame: 1 year after LPI ]
    ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters)

  3. Serum Biomarkers [ Time Frame: 1 year after LPI ]
    To explore the relationship between the baseline level and dynamic changes of serum markers(AFP and PIVKA-II) and therapeutic response, Peripheral blood serum was collected at baseline and at each follow-up visit.

  4. Adverse events(AE) and Serious adverse events(SAE) [ Time Frame: 1 year after LPI ]

    An adverse event (AE) refers to any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, but which does not necessarily have a causal relationship with this treatment.

    A serious adverse event (SAE) refers to an event in clinical trials that requires inpatient hospitalization or causes prolongation of existing hospitalization, permanent disability, incapacity, threats to life or death, and birth defect, etc.

    Number and classification of participants with treatment-related adverse events as assessed by CTCAE v4.0 were recorded.


  5. Health-related quality of life: EORTC QLQ-HCC18 [ Time Frame: 1 year after LPI ]
    Health-related quality of life questionnaire measured by EORTC QLQ-HCC18.

  6. Exploratory serum biomarker research [ Time Frame: 1 year after LPI ]
    About 10 mL peripheral blood will be collected at baseline and at each follow-up visit. The correlations between serum biomarkers at baseline or the dynamic changes and treatment response will be analyzed.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female aged 18-75;
  2. The participant must have confirmed diagnosis of HCC histologically or clinically;
  3. The participant must have at least one untreated intrahepatic lesion that can be evaluated by contrast-enhanced CT or MRI;
  4. The BCLC stage B/C patients, more than 3 tumor nodes or have portal vein tumor thrombus (Vp3-Vp4 according to LCSGJ PVTT classification) or extrahepatic metastases limited to one organ and the number of metastases nodules is no more than 3;
  5. ECOG PS 0-1 and Child-Pugh A;
  6. Surgical resection is not the first choice according to MDT evaluation;
  7. Written informed consent;

Exclusion Criteria:

  1. WBC<4.0*10^9/L, HB<80 g/L, PLT<75*10^9/L and NEUT<1.5×10^9/L;
  2. Coagulation function: (prothrombin time) international normalized ratio (INR) >1.2;
  3. Liver function: serum albumin (ALB)<3.5 g/dl, total bilirubin (TBIL)>1.5 times the upper limit of normal range, alanine aminotransferase and aspartate aminotransferase (ALT and AST)>3 times the upper limit of normal range; renal function index: serum creatinine (CRE)>1.5 times the upper limit of normal range; uncontrolled hypertension (>150/90mm Hg);
  4. Lymph node metastasis to hilar of lung or liver, or peripheral tissue adhesion;
  5. Participated in other clinical trials 30 days before enrollment;
  6. With ascites, hepatic encephalopathy, Gilbert syndrome, sclerosing cholangitis;
  7. Suspected allergy to study drug;
  8. With other organ dysfunction, it is not expected to be tolerated general anesthesia or hepatectomy;
  9. Other conditions that the investigators considered not unsuitable for inclusion.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04241523


Contacts
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Contact: Jian Zhou 0086-21-64041990 zhou.jian@zs-hospital.sh.cn
Contact: Huichuan Sun 0086-21-64041990 sun.huichuan@zs-hospital.sh.cn

Locations
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China, Anhui
Anhui Provincial Hospital Recruiting
Hefei, Anhui, China, 230000
Contact: Lianxin Liu         
Contact: Weidong Jia         
China, Hubei
Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Recruiting
Wuhan, Hubei, China, 430000
Contact: Zhiyong Huang         
China, Sichuan
West China Hospital Recruiting
Chengdu, Sichuan, China, 610000
Contact: Tianfu Wen         
China
180 Fenglin Road Recruiting
Shanghai, China, 200032
Contact: Jian Zhou    0086-21-64041990    zhou.jian@zs-hospital.sh.cn   
Contact: Huichuan Sun    0086-21-64041990    sun.huichuan@zs-hospital.sh.cn   
Principal Investigator: Jian Zhou         
Principal Investigator: Huichuan Sun         
Sponsors and Collaborators
Shanghai Zhongshan Hospital
Tongji Hospital
Anhui Provincial Hospital
West China Hospital
Investigators
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Principal Investigator: Jian Zhou Shanghai Zhongshan Hospital
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Responsible Party: Jian Zhou, Professor of Surgery, Shanghai Zhongshan Hospital
ClinicalTrials.gov Identifier: NCT04241523    
Other Study ID Numbers: HCC-LEN-Conversion
First Posted: January 27, 2020    Key Record Dates
Last Update Posted: January 27, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Lenvatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action