Durvalumab and Lenvatinib in Participants With Locally Advanced and Metastatic Hepatocellular Carcinoma ( Dulect2020-1 )

NCT04443322 | Unknown

• 1 other identifier: RenJi-IIT-2020-0006
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Liver Carcinoma; Liver Transplant; Complications

Keywords

liver cancer; liver transplant

Outcome Measures

Primary Outcomes (2)

• Progression Free Survival (PFS)

  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)

  Up to 3 years

• Recurrence-Free Survival (RFS)

  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)

  Up to 4 years

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  Up to 1 year

• Overall Survival (OS)

  Up to 5 years

• Percentage of Participants who Experience an Adverse Event (AE)

  Up to 2 years

Study Arms (1)

Durvalumab and Lenvatinib

EXPERIMENTAL

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).

Drug: Durvalumab Injection; Drug: Lenvatinib 4 MG

Interventions

Durvalumab Injection DRUG

Anti-PD-L1 Monoclonal Antibody

Also known as: Durvalumab, Imfinzi

Durvalumab and Lenvatinib

Lenvatinib 4 MG DRUG

Lenvatinib (Lenvima, Eisai China) is a novel angiogenesis inhibitor which targets vascular endothelial growth factor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor β etc.

Also known as: Lenvima

Durvalumab and Lenvatinib

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 1.
• Has a Child-Pugh A liver score (5 to 6 points) within 7 days prior to Cycle1, Day 1.
• 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.
• Granulocytes \>= 1,500/uL
• Hemoglobin \>= 8.5 g/dL; patients with recent or ongoing gastrointestinal bleed may not be transfused to reach the entry hemoglobin of 8.5 g/dL; physicians should ensure patients requiring transfusion prior to registration do not have an occult or clinically apparent gastrointestinal bleed
• Platelets \>= 75,000/uL
• Creatinine =\< 1.5 x upper limit of normal (ULN) (or creatinine clearance calculated \>= 60 cc/minute)
• Bilirubin =\< 3 mg/dL

You may not qualify if:

• 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).
• Has received prior systemic anti-cancer therapy for HCC including investigational agents.
• Is receiving any of the following prohibited concomitant therapies:1) Antineoplastic systemic chemotherapy or biological therapy; 2) Immunotherapy not specified in this protocol; 3) Investigational agents other than pembrolizumab; 4) Radiation therapy; 5) Oncological surgical therapy; or systemic glucocorticoids for any purpose other than to modulate symptoms from an AE that is suspected to have an immunologic etiology.
• Has received a live vaccine within 30 days prior to the first dose of study treatment.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to Cycle 1, Day 1.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to Cycle 1, Day 1.

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (1)

Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University

Shanghai, 200127, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

durvalumab; lenvatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Jian-jun Zhang, MD

  Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTU

  STUDY DIRECTOR

• Qiang Xia, MD

  Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTU

  STUDY CHAIR

• Hao Feng, MD., Ph.D.

  Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTU

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hao Feng, MD., Ph.D.

CONTACT

008615000901110; surgeonfeng@live.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2020
• First Posted: June 23, 2020
• Study Start: September 19, 2020
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2025
• Last Updated: September 22, 2020

Record last verified: 2020-06

Locations

CN (1)