search
Back to results

Efficacy and Safety of Lenvatinib as a Conversion Therapy for HCC

Primary Purpose

Hepatocellular Carcinoma (HCC)

Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Lenvatinib 4 mg Oral
Sponsored by
Shanghai Zhongshan Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma (HCC)

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Anhui Provincial HospitalRecruiting
  • Tongji Hospital, Tongji Medical College Huazhong University of Science and TechnologyRecruiting
  • West China HospitalRecruiting
  • 180 Fenglin RoadRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

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.

Outcomes

Primary Outcome Measures

Resection rate
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

Overall survival (OS)
The duration from the date of recruitment to the date of death from any cause.
Objective response rate (ORR)
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)
Serum Biomarkers
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.
Adverse events(AE) and Serious adverse events(SAE)
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.
Health-related quality of life: EORTC QLQ-HCC18
Health-related quality of life questionnaire measured by EORTC QLQ-HCC18.
Exploratory serum biomarker research
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.

Full Information

First Posted
January 22, 2020
Last Updated
January 24, 2020
Sponsor
Shanghai Zhongshan Hospital
Collaborators
Tongji Hospital, Anhui Provincial Hospital, West China Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT04241523
Brief Title
Efficacy and Safety of Lenvatinib as a Conversion Therapy for HCC
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Unknown status
Study Start Date
January 2020 (Anticipated)
Primary Completion Date
October 2021 (Anticipated)
Study Completion Date
February 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Zhongshan Hospital
Collaborators
Tongji Hospital, Anhui Provincial Hospital, West China Hospital

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma (HCC)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Lenvatinib 4 mg Oral
Other Intervention Name(s)
Lenvima 4 mg Oral
Intervention Description
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.
Primary Outcome Measure Information:
Title
Resection rate
Description
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).
Time Frame
1 year after LPI
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
The duration from the date of recruitment to the date of death from any cause.
Time Frame
3 years
Title
Objective response rate (ORR)
Description
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)
Time Frame
1 year after LPI
Title
Serum Biomarkers
Description
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.
Time Frame
1 year after LPI
Title
Adverse events(AE) and Serious adverse events(SAE)
Description
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.
Time Frame
1 year after LPI
Title
Health-related quality of life: EORTC QLQ-HCC18
Description
Health-related quality of life questionnaire measured by EORTC QLQ-HCC18.
Time Frame
1 year after LPI
Title
Exploratory serum biomarker research
Description
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.
Time Frame
1 year after LPI

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female aged 18-75; The participant must have confirmed diagnosis of HCC histologically or clinically; The participant must have at least one untreated intrahepatic lesion that can be evaluated by contrast-enhanced CT or MRI; 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; ECOG PS 0-1 and Child-Pugh A; Surgical resection is not the first choice according to MDT evaluation; Written informed consent; Exclusion Criteria: WBC<4.0*10^9/L, HB<80 g/L, PLT<75*10^9/L and NEUT<1.5×10^9/L; Coagulation function: (prothrombin time) international normalized ratio (INR) >1.2; 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); Lymph node metastasis to hilar of lung or liver, or peripheral tissue adhesion; Participated in other clinical trials 30 days before enrollment; With ascites, hepatic encephalopathy, Gilbert syndrome, sclerosing cholangitis; Suspected allergy to study drug; With other organ dysfunction, it is not expected to be tolerated general anesthesia or hepatectomy; Other conditions that the investigators considered not unsuitable for inclusion.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jian Zhou
Phone
0086-21-64041990
Email
zhou.jian@zs-hospital.sh.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Huichuan Sun
Phone
0086-21-64041990
Email
sun.huichuan@zs-hospital.sh.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jian Zhou
Organizational Affiliation
Shanghai Zhongshan Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Anhui Provincial Hospital
City
Hefei
State/Province
Anhui
ZIP/Postal Code
230000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lianxin Liu
First Name & Middle Initial & Last Name & Degree
Weidong Jia
Facility Name
Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhiyong Huang
Facility Name
West China Hospital
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tianfu Wen
Facility Name
180 Fenglin Road
City
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jian Zhou
Phone
0086-21-64041990
Email
zhou.jian@zs-hospital.sh.cn
First Name & Middle Initial & Last Name & Degree
Huichuan Sun
Phone
0086-21-64041990
Email
sun.huichuan@zs-hospital.sh.cn
First Name & Middle Initial & Last Name & Degree
Jian Zhou
First Name & Middle Initial & Last Name & Degree
Huichuan Sun

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Efficacy and Safety of Lenvatinib as a Conversion Therapy for HCC

We'll reach out to this number within 24 hrs