search
Back to results

Lenvatinib Plus PD-1 Antibody Versus Lenvtinib Alone for Advanced HCC

Primary Purpose

Hepatocellular Carcinoma

Status
Withdrawn
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Lenvatinib
PD-1 antibody
Placebo
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Hepatocellular Carcinoma, Lenvatinib, PD-1 Antibody

Eligibility Criteria

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

Inclusion Criteria:

  • The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL)
  • Patients must have at least one tumor lesion that can be accurately measured according to EASL criteria.
  • Barcelona clinic liver cancer-stage C
  • Eastern Cooperative Oncology Group performance status of 0 to 2
  • with no previous treatment
  • No Cirrhosis or cirrhotic status of Child-Pugh class A only
  • Not amendable to surgical resection ,local ablative therapy and any other cured treatment.
  • The following laboratory parameters:
  • Platelet count ≥ 75,000/μL
  • Hemoglobin ≥ 8.5 g/dL
  • Total bilirubin ≤ 30mmol/L
  • Serum albumin ≥ 30 g/L
  • ASL and AST ≤ 5 x upper limit of normal
  • Serum creatinine ≤ 1.5 x upper limit of normal
  • INR ≤ 1.5 or PT/APTT within normal limits
  • Absolute neutrophil count (ANC) >1,500/mm3
  • Ability to understand the protocol and to agree to and sign a written informed consent document

Exclusion Criteria:

  • Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy
  • Known history of HIV
  • History of organ allograft
  • Known or suspected allergy to the investigational agents or any agent given in association with this trial.
  • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
  • Evidence of bleeding diathesis.
  • Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.
  • Known central nervous system tumors including metastatic brain disease

Sites / Locations

  • Cancer Center Sun Yat-sen University
  • The First Affiliated Hospital of Sun Yat-sen University
  • Guangzhou Twelfth People 's Hospita
  • Kaiping Central Hospital
  • First Affiliated Hospital of University Of South China

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Lenvatinib Plus PD-1

Lenvatinib alone

Arm Description

Participants received lenvatinib capsules 12 milligram (mg) based on the participant's body weight greater than or equal to (>=) 60 kilogram (kg) or 8 mg based on the participant's body weight less than (<) 60 kg at baseline, orally, once daily (QD) in continuous 14-day treatment cycles, and received 3mg/kg PD-1 antibody intravenously every 2 weeks up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.

Participants received lenvatinib capsules 12 milligram (mg) based on the participant's body weight greater than or equal to (>=) 60 kilogram (kg) or 8 mg based on the participant's body weight less than (<) 60 kg at baseline, orally, once daily (QD) in continuous 14-day treatment cycles, and received placebo intravenously every 2 weeks up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.

Outcomes

Primary Outcome Measures

Overall Survival (OS)
OS was defined as the duration from the date of randomization until the date of death from any cause. Participants who were lost to follow-up were censored at the last date the participant was known to be alive, and participants who remained alive were censored at the time of data cutoff.

Secondary Outcome Measures

Progression Free Survival (PFS)
PFS was defined as the time from the date of randomization to the date of first documentation of disease progression based on modified Response Evaluation Criteria in Solid Tumors (mRECIST), or date of death, whichever occurred first.
Objective Response Rate (ORR)
ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) based on mRECIST. CR was defined as disappearance of any intratumoral arterial enhancement in all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of viable (enhancement of arterial phase) target lesions taking as reference to the baseline sum of the diameters of target lesions.
Adverse Events
Number of adverse events. Postoperative adverse events were graded based on CTCAE v4.03
Time to Progression (TTP)
TTP was defined as the time from the date of randomization to the date of first documentation of disease progression based on mRECIST.

Full Information

First Posted
November 14, 2018
Last Updated
April 30, 2019
Sponsor
Sun Yat-sen University
Collaborators
First Affiliated Hospital, Sun Yat-Sen University, Kaiping Central Hospital, Guangzhou No.12 People's Hospital, The First Affiliated Hospital of University of South China
search

1. Study Identification

Unique Protocol Identification Number
NCT03744247
Brief Title
Lenvatinib Plus PD-1 Antibody Versus Lenvtinib Alone for Advanced HCC
Official Title
Lenvatinib Plus Programmed Cell Death Protein-1 (PD-1) Inhibitor Versus Lenvtinib Alone for Advanced Hepatocellular Carcinoma: a Multicentre Randomised Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Withdrawn
Why Stopped
No paritcipants enrolled
Study Start Date
April 21, 2019 (Anticipated)
Primary Completion Date
January 1, 2021 (Anticipated)
Study Completion Date
June 1, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University
Collaborators
First Affiliated Hospital, Sun Yat-Sen University, Kaiping Central Hospital, Guangzhou No.12 People's Hospital, The First Affiliated Hospital of University of South China

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to evaluate the efficacy and safety of lenvatinib combined with PD-1 antibody compared with lenvtinib Alone in patients with advanced hepatocellular carcinoma (HCC)
Detailed Description
Lenvatinib was non-inferior to sorafenib in overall survival in untreated advanced hepatocellular carcinoma, and PD-1 antibody was effective and tolerable in patients with advanced hepatocellular carcinoma. No study has compared the efficacy and safety of lenvatinib plus PD-1 antibody and lenvatinib alone. Thus, the investigators carried out this prospective randomized control study to find out it.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
Hepatocellular Carcinoma, Lenvatinib, PD-1 Antibody

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lenvatinib Plus PD-1
Arm Type
Experimental
Arm Description
Participants received lenvatinib capsules 12 milligram (mg) based on the participant's body weight greater than or equal to (>=) 60 kilogram (kg) or 8 mg based on the participant's body weight less than (<) 60 kg at baseline, orally, once daily (QD) in continuous 14-day treatment cycles, and received 3mg/kg PD-1 antibody intravenously every 2 weeks up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
Arm Title
Lenvatinib alone
Arm Type
Active Comparator
Arm Description
Participants received lenvatinib capsules 12 milligram (mg) based on the participant's body weight greater than or equal to (>=) 60 kilogram (kg) or 8 mg based on the participant's body weight less than (<) 60 kg at baseline, orally, once daily (QD) in continuous 14-day treatment cycles, and received placebo intravenously every 2 weeks up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
Intervention Type
Drug
Intervention Name(s)
Lenvatinib
Other Intervention Name(s)
E7080, Lenvima
Intervention Description
12 mg (or 8 mg) once daily (QD) oral dosing.
Intervention Type
Drug
Intervention Name(s)
PD-1 antibody
Other Intervention Name(s)
Programmed cell death 1 antibody
Intervention Description
3mg/kg intravenously every 2 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Intravenously every 2 weeks
Primary Outcome Measure Information:
Title
Overall Survival (OS)
Description
OS was defined as the duration from the date of randomization until the date of death from any cause. Participants who were lost to follow-up were censored at the last date the participant was known to be alive, and participants who remained alive were censored at the time of data cutoff.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
PFS was defined as the time from the date of randomization to the date of first documentation of disease progression based on modified Response Evaluation Criteria in Solid Tumors (mRECIST), or date of death, whichever occurred first.
Time Frame
12 months
Title
Objective Response Rate (ORR)
Description
ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) based on mRECIST. CR was defined as disappearance of any intratumoral arterial enhancement in all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of viable (enhancement of arterial phase) target lesions taking as reference to the baseline sum of the diameters of target lesions.
Time Frame
12 months
Title
Adverse Events
Description
Number of adverse events. Postoperative adverse events were graded based on CTCAE v4.03
Time Frame
30 days
Title
Time to Progression (TTP)
Description
TTP was defined as the time from the date of randomization to the date of first documentation of disease progression based on mRECIST.
Time Frame
12 months

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: The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL) Patients must have at least one tumor lesion that can be accurately measured according to EASL criteria. Barcelona clinic liver cancer-stage C Eastern Cooperative Oncology Group performance status of 0 to 2 with no previous treatment No Cirrhosis or cirrhotic status of Child-Pugh class A only Not amendable to surgical resection ,local ablative therapy and any other cured treatment. The following laboratory parameters: Platelet count ≥ 75,000/μL Hemoglobin ≥ 8.5 g/dL Total bilirubin ≤ 30mmol/L Serum albumin ≥ 30 g/L ASL and AST ≤ 5 x upper limit of normal Serum creatinine ≤ 1.5 x upper limit of normal INR ≤ 1.5 or PT/APTT within normal limits Absolute neutrophil count (ANC) >1,500/mm3 Ability to understand the protocol and to agree to and sign a written informed consent document Exclusion Criteria: Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy Known history of HIV History of organ allograft Known or suspected allergy to the investigational agents or any agent given in association with this trial. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy Evidence of bleeding diathesis. Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry. Known central nervous system tumors including metastatic brain disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ming Shi, MD
Organizational Affiliation
The Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cancer Center Sun Yat-sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Facility Name
The First Affiliated Hospital of Sun Yat-sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Facility Name
Guangzhou Twelfth People 's Hospita
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510620
Country
China
Facility Name
Kaiping Central Hospital
City
Kaiping
State/Province
Guangdong
ZIP/Postal Code
529300
Country
China
Facility Name
First Affiliated Hospital of University Of South China
City
Hengyang
State/Province
Hunan
ZIP/Postal Code
421001
Country
China

12. IPD Sharing Statement

Learn more about this trial

Lenvatinib Plus PD-1 Antibody Versus Lenvtinib Alone for Advanced HCC

We'll reach out to this number within 24 hrs