Phase II of Lenvatinib Plus PD-1 Antibody for Advanced HCC

• ClinicalTrials.gov Identifier: NCT03746249
• Recruitment Status: Withdrawn
• First Posted: November 19, 2018
• Last Update Posted: April 17, 2019
• Sponsor: Sun Yat-sen University
• Information provided by (Responsible Party): Shi Ming, Sun Yat-sen University

Study Description

Brief Summary:

The purpose of this study is to evaluate the efficacy and safety of lenvatinib combined with PD-1 antibody in patients with advanced hepatocellular carcinoma (HCC)

Condition or disease	Intervention/treatment	Phase
Hepatocellular Carcinoma	Drug: Lenvatinib; Drug: PD-1 antibody	Phase 2

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 evaluated the efficacy and safety of lenvatinib plus PD-1 antibody. Thus, the investigators carried out this single-arm, prospective, phase II study to find out it.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II of Lenvatinib Plus Programmed Cell Death 1 Antibody for Advanced Hepatocellular Carcinoma
• Actual Study Start Date: December 17, 2018
• Estimated Primary Completion Date: August 1, 2019
• Estimated Study Completion Date: December 1, 2019

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 Name: E7080, Lenvima; Drug: PD-1 antibody; 3mg/kg intravenously every 2 weeks; Other Name: Programmed cell death 1 antibody

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival (PFS) [ Time Frame: 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.

Secondary Outcome Measures :

1. Objective Response Rate (ORR) [ Time Frame: 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.
2. Overall Survival (OS) [ Time Frame: 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.
3. Time to Progression (TTP) [ Time Frame: 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.
4. Adverse Events [ Time Frame: 30 days ]
   Number of adverse events. Postoperative adverse events were graded based on CTCAE v4.03

Eligibility Criteria

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

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

Contacts and Locations

Locations

China, Guangdong

Cancer Center Sun Yat-sen University

Guangzhou, Guangdong, China, 510060

Sponsors and Collaborators

Sun Yat-sen University

Investigators

• Principal Investigator: Ming Shi, MD; The Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center

More Information

• Responsible Party: Shi Ming, Proffessor, Sun Yat-sen University
• ClinicalTrials.gov Identifier: NCT03746249
• Other Study ID Numbers: HCC-S052
• First Posted: November 19, 2018
• Last Update Posted: April 17, 2019
• Last Verified: April 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shi Ming, Sun Yat-sen University:

Hepatocellular Carcinoma; Lenvatinib; PD-1 Antibody

Additional relevant MeSH terms:

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; Antibodies; Immunoglobulins; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action