A Study on the Efficiency and Safety of Durvalumab Plus Lenvatinib as First-line Treatment for Unresectable Hepatocellular Carcinoma: an Open, Single Arm, Phase II Clinical Trial
Overview
- Phase
- Phase 2
- Intervention
- Durvalumab plus Lenvatinib
- Conditions
- Hepatocellular Carcinoma
- Sponsor
- Zhejiang University
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Objective response rate (ORR)
- Status
- Not yet recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a phase II, open-label study to evaluate the efficacy and safety of Durvalumab plus Lenvatinib as first-line treatment in patients with unresectable hepatocellular carcinoma.
Detailed Description
This single-arm, open-label, prospective phase II clinical trial was designed to evaluate the efficacy and safety of Durvalumab plus Lenvatinib as first-line treatment in patients with unresectable hepatocellular carcinoma. The primary endpoint is the objective response rate (ORR) according to RECIST v1.1. Safety evaluation will be taken according to CTCAE v5.0. Disease control rate (DCR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS) are secondary endpoints. Multi-omics analysis will be performed to identify potential biomarkers for treatment response.
Investigators
TingBo Liang
The chairman of the First Affiliated Hospital of Zhejiang
Zhejiang University
Eligibility Criteria
Inclusion Criteria
- •Subjects volunteer to participate in the study and sign the informed consent before enrollment.
- •18-80 years of age.
- •ECOG score of 0-
- •Primary liver cancer with a pathological diagnosis of hepatocellular carcinoma.
- •Child-Pugh grade A (5-6 points).
- •BCLC C stage or BCLC B stage not suitable/refused for locoreginal treatments.
- •Tumor volume ≤ 50% of the total liver volume.
- •Without prior systemic therapy and unwilling to receive standard systemic therapy or unsuitable for standard systemic therapy.
- •At least one measurable lesion as defined by RECIST v1.1 criteria.
- •Patients infected with hepatitis virus should receive antiviral therapy regularly.
Exclusion Criteria
- •Patients with any active autoimmune disease or history of autoimmune disease (e.g. the following but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enterocolitis, autoimmune hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, vitiligo. Patients with complete remission of asthma in childhood who do not require any intervention in adulthood may be included, but those require bronchodilators cannot be included.
- •Patients who are on immunosuppressive drugs, or require systemic hormone therapy for immunosuppression purposes (doses \>10 mg/day of prednisone or other isotonic hormones) and who continue to use them within 2 weeks prior to enrollment.
- •Receiving systemic therapy previously or other anti-cancer treatments (e.g. radiofrequency ablation, interventional therapy, radiotherapy, etc.)
- •Patients with a known history of central neural system metastases or hepatic encephalopathy.
- •Patients with clinically symptomatic ascites requiring puncture or drainage or those who have received ascites drainage within the previous 3 months.
- •Patients with hypertension that is not well controlled by antihypertensive medication (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg).
- •Having clinical cardiac symptoms or disease not well controlled, such as (1) NYHA class 2 or higher heart failure (2) unstable angina pectoris (3) myocardial infarction within 1 year (4) clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention (5) QTc \> 450 ms (men); QTc \> 470 ms (women).
- •With abnormal coagulation (INR \> 2.0, PT \> 16s), bleeding tendency or on thrombolytic or anticoagulant therapy. Prophylactic use of low-dose aspirin or low molecular heparin is allowed.
- •Patients had clinically significant bleeding symptoms or a clear bleeding tendency within the 3 months prior to enrollment.
- •Having arterial/venous thrombotic events within the 6 months prior to enrollment.
Arms & Interventions
Durvalumab plus Lenvatinib
Durvalumab is a human IgG1 κ monoclonal antibody that inhibits binding of PD-L1 to its receptors PD-1 and CD80. Lenvatinib is a multi- kinase inhibitor of VEGF receptors 1 to 3, FGF receptors 1 to 4, PDGFRa, RET, and KIT.
Intervention: Durvalumab plus Lenvatinib
Outcomes
Primary Outcomes
Objective response rate (ORR)
Time Frame: up o one year
The proportion of patients who had tumor response evaluated as CR or PR according to RECIST v1.1 during study.
Secondary Outcomes
- Disease control rate (DCR)(up to one year)
- Duration of response (DOR)(up to one year)
- Progression-free survival (PFS)(up to one year)
- Overall survival (OS)(up to two years)
- Adverse events (AEs)(up to two years)