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

Sponsor

Sun Yat-sen University (Other)

Overall Status

Withdrawn

CT.gov ID

NCT03744247

Collaborator

First Affiliated Hospital, Sun Yat-Sen University (Other), Kaiping Central Hospital (Other), Guangzhou No.12 People's Hospital (Other), The First Affiliated Hospital of University of South China (Other)

Enrollment

Locations

Arms

25.4

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

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)

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: Lenvatinib Drug: PD-1 antibody Drug: Placebo	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Lenvatinib Plus Programmed Cell Death Protein-1 (PD-1) Inhibitor Versus Lenvtinib Alone for Advanced Hepatocellular Carcinoma: a Multicentre Randomised Controlled Trial

Anticipated Study Start Date :

Apr 21, 2019

Anticipated Primary Completion Date :

Jan 1, 2021

Anticipated Study Completion Date :

Jun 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lenvatinib Plus PD-1 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.	Drug: Lenvatinib 12 mg (or 8 mg) once daily (QD) oral dosing. Other Names: E7080, Lenvima Drug: PD-1 antibody 3mg/kg intravenously every 2 weeks Other Names: Programmed cell death 1 antibody
Active Comparator: Lenvatinib alone 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.	Drug: Lenvatinib 12 mg (or 8 mg) once daily (QD) oral dosing. Other Names: E7080, Lenvima Drug: Placebo Intravenously every 2 weeks

Arm

Intervention/Treatment

Experimental: Lenvatinib Plus PD-1

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.

Drug: Lenvatinib

12 mg (or 8 mg) once daily (QD) oral dosing.

Other Names:

E7080, Lenvima

Drug: PD-1 antibody

3mg/kg intravenously every 2 weeks

Other Names:

Programmed cell death 1 antibody

Active Comparator: Lenvatinib alone

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.

Drug: Lenvatinib

12 mg (or 8 mg) once daily (QD) oral dosing.

Other Names:

E7080, Lenvima

Drug: Placebo

Intravenously every 2 weeks

Outcome Measures

Primary Outcome Measures

Overall Survival (OS) [12 months]
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) [12 months]
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) [12 months]
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 [30 days]
Number of adverse events. Postoperative adverse events were graded based on CTCAE v4.03
Time to Progression (TTP) [12 months]
TTP was defined as the time from the date of randomization to the date of first documentation of disease progression based on mRECIST.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cancer Center Sun Yat-sen University	Guangzhou	Guangdong	China	510060
2	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong	China	510060
3	Guangzhou Twelfth People 's Hospita	Guangzhou	Guangdong	China	510620
4	Kaiping Central Hospital	Kaiping	Guangdong	China	529300
5	First Affiliated Hospital of University Of South China	Hengyang	Hunan	China	421001