Safety and Efficacy Study of Durvalumab in Combination With Lenvatinib in Participants With Locally Advanced and Metastatic Hepatocellular Carcinoma-- DULECT2020-1 Trial
Overview
- Phase
- Not Applicable
- Intervention
- Lenvatinib 4 MG
- Conditions
- Liver Carcinoma
- Sponsor
- RenJi Hospital
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Progression Free Survival (PFS)
- Status
- Recruiting
- Last Updated
- 5 years ago
Overview
Brief Summary
This study will evaluate the safety and efficacy of durvalumab in combination with lenvatinib in participants with locally advanced hepatocellular carcinoma before liver transplant and metastatic unresectable HCC.The primary hypothesis of this study are that patients with locally advanced HCC could benefit from durvalumab plus lenvatinib before liver transplant; patients with metastatic unresectable HCC could also benefit from durvalumab plus lenvatinib with respect to: 1)Progression Free Survival (PFS) ; or recurrence-free survival (RFS) if patients with locally advanced HCC underwent liver transplant; 2) Objective Response Rate (ORR); and 3) Overall survival (OS). The investigators design a clinical study to explore whether the combination above as a treatment in patients with advanced and recurrent endometrial carcinoma could prolong PFS and to analyze potential immune biomarker of therapeutic response.
Detailed Description
The combination of Lenvatinib and Programmed death-ligand 1 (PD-L1) blocking has great potential in the treatment of locally advanced hepatocellular carcinoma before liver transplant and metastatic unresectable HCC. This trial is designed as a prospective, open label study for 20 patients with locally advanced hepatocellular carcinoma before liver transplant and metastatic unresectable HCC. The aim is to investigate the efficacy of the combination therapy of Lenvatinib 80-120mg daily orally and durvalumab 1500mg by IV infusion every 4 weeks in terms of progression free survival.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have pathologically or cytologically or by radiological criteria proven hepatocellular carcinoma; known mixed histology (e.g. hepatocellular carcinoma plus cholangiocarcinoma) or fibrolamellar variant is not allowed
- •Locally advanced and metastatic HCC
- •Has an eligibility scan (CT of the chest, triphasic CT scan or MRI of the abdomen, and CT or MRI of the pelvis) \<1 week before the treatment of durvalumab in combination with lenvatinib.
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to Cycle 1, Day
- •Has a Child-Pugh A liver score (5 to 6 points) within 7 days prior to Cycle1, Day
- •Has controlled hepatitis B (Hep B)
- •The estimate time length between enrollment and liver transplantation should be at least 2 months
- •No prior systemic therapy, local therapy (TACE etc.)\>6w
- •If female, is not pregnant or breastfeeding, and at least one of the following conditions applies: 1) Is not a woman of childbearing potential (WOCBP); or 2) Is a WOCBP and using a contraceptive method that is highly effective or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (a WOCBP must have a negative pregnancy test within 72 hours before the first dose of study treatment).
- •Has adequate organ function.
Exclusion Criteria
- •Has had esophageal or gastric variceal bleeding within the last 6 months.
- •Has clinically apparent ascites on physical examination.
- •Has had clinically diagnosed hepatic encephalopathy in the last 6 months.
- •Has received local therapy to liver ablation other than with radiofrequency or microwave ablation.
- •Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
- •Has an active infection requiring systemic therapy.
- •Has dual active Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection at study entry.
- •Has a known history of human immunodeficiency virus (HIV) infection.
- •Has known active tuberculosis (TB; Bacillus tuberculosis).
- •Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
Arms & Interventions
Durvalumab and Lenvatinib
Participants receive intravenous (IV) durvalumab at 1500mg on Day 1 of each 28-day cycle. Number of cycles: until unacceptable toxicity develops or \>42 days before liver transplantation (If patients with locally advanced HCC would undergo liver transplant). Patients receive Lenvatinib 8-12mg(basing on weight), once a day, oral at least 38 days of each 6 weeks cycle until \>7 days before liver transplantation(If patients with locally advanced HCC would undergo liver transplant).
Intervention: Lenvatinib 4 MG
Durvalumab and Lenvatinib
Participants receive intravenous (IV) durvalumab at 1500mg on Day 1 of each 28-day cycle. Number of cycles: until unacceptable toxicity develops or \>42 days before liver transplantation (If patients with locally advanced HCC would undergo liver transplant). Patients receive Lenvatinib 8-12mg(basing on weight), once a day, oral at least 38 days of each 6 weeks cycle until \>7 days before liver transplantation(If patients with locally advanced HCC would undergo liver transplant).
Intervention: Durvalumab Injection
Outcomes
Primary Outcomes
Progression Free Survival (PFS)
Time Frame: Up to 3 years
Defined as time from randomisation to first progression by investigator assessment using modified RECIST 1.1 or death (by any cause in the absence of progression)
Recurrence-Free Survival (RFS)
Time Frame: Up to 4 years
If patients with locally advanced HCC would undergo liver transplant after neoadjuvant treatment of Durvalumab and Lenvatinib.RFS is defined as the time from randomization to first documentation of disease recurrence (local, regional, or distant) as assessed by BICR or by pathology consistent with HCC if required per the site's standard of care, or death due to any cause (both cancer and non-cancer causes of death)
Secondary Outcomes
- Percentage of Participants who Experience an Adverse Event (AE)(Up to 2 years)
- Objective Response Rate (ORR)(Up to 1 year)
- Overall Survival (OS)(Up to 5 years)