Lenvatinib Combined Pembrolizumab as a Second-line Treatment in Advanced Hepatobiliary Tumors: a Single-center, Single-arm, Non-randomized Clinical Study
Overview
- Phase
- Phase 2
- Intervention
- Lenvatinib plus Pembrolizumab
- Conditions
- Liver Neoplasm Malignant Primary
- Sponsor
- Peking Union Medical College Hospital
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Objective Response Rate (ORR)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The investigators design a phase IIB clinical study to explore the efficacy and safety of lenvatinib plus pembrolizumab as a second-line treatment in patients with advanced hepatobiliary malignant tumors and to analyze potential biomarkers of therapeutic response.
Detailed Description
This trial is a single-arm, non-randomized and single-center clinical study of targeted therapy combined immunotherapy in patients with hepatobiliary malignant tumors. It is estimated that 50 patients who met the study criteria will be enrolled in PUMCH and treated with lenvatinib and pembrolizumab. The investigators will follow up and collect subjects' data each month to evaluate the efficacy and safety of treatment, including overall survival and time to progression. Multi-omics data analysis will be used to find potential biomarkers of treatment response.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects must meet all of the following criteria
- •Subjects volunteer to participate in the study and agree to sign the informed consent with good compliance and follow-up.
- •Subjects are 18 years old or older when signing the informed consent and gender is not limited.
- •Subjects were diagnosed with advanced hepatobiliary malignant tumors (clinical stage IV) by imaging and histological examination, including hepatocellular carcinoma, cholangiocarcinoma, ampullary carcinoma, gallbladder carcinoma and mixed carcinoma.
- •The disease is not suitable for radical surgery and/or topical treatment, or disease progression occurs after surgery and/or local treatment.
- •At least one measurable lesion (according to RECIST version 1.1): the measurable lesion has a long diameter ≥ 10 mm or lymphadenpathy has a short diameter ≥ 15 mm in spiral CT scan.
- •Patients fail after at least one systemic failure, including surgery, intervention, radiotherapy, chemotherapy and targeted therapy and require palliative treatment.
- •Definition of treatment failure: Disease progression during treatment or relapse after treatment, such as after at least once radical or palliative resection surgery, revenue recurrence or progression after intervention therapy or radiotherapy. Intervention therapy or oxaliplatin treatment must be more than 1 cycle, and molecular targeted therapy must more than ≥14 days.
- •Definition of intolerance: Grade ≥IV hematologic toxicity, or grade ≥III non- hematologic toxicity, or grade ≥ II damage of heart, liver and kidney during treatment.
- •The ECOG score is 0-2 within 1 week before enrollment.
Exclusion Criteria
- •Subjects with one or more than one of the following criteria should be excluded
- •Clinical stage I-III, and/or with any of the following:
- •Suitable for radical surgery,
- •Or, without an assessment lesion after radical surgery,
- •Or, never receive any first line treatment,
- •Or, liver transplantation history or ready for liver transplantation.
- •ECOG score ≥ 3 points.
- •Received any topical treatment within 4 weeks prior to the study, including but not limited to surgery, radiotherapy, hepatic artery embolization, TACE, hepatic artery perfusion, radiofrequency ablation, cryoablation or percutaneous ethanol injection.
- •Ascites with clinical symptoms which requires abdominal puncture or drainage therapy, or Child-Pugh score \>
- •With serious systemic diseases such as heart disease and cerebrovascular disease, and the condition is unstable or uncontrollable.
Arms & Interventions
Lenvatinib plus Pembrolizumab
Lenvatinib 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, RET and KIT. Pembrolizumab is a recombinant anti-human PD-1 monoclonal antibody.
Intervention: Lenvatinib plus Pembrolizumab
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: one year
Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients.
Progression-free Survival (PFS)
Time Frame: six months
A duration from the date of initial treatment with lenvatinib plus pembrolizumab to disease progression (defined by RECIST 1.1) or death of any cause.
Disease Control Rate (DCR)
Time Frame: one year
Proportion of patients whose tumor volume control (reduced or enlarged) reaches a predetermined value and can maintain a minimum time limit.
Secondary Outcomes
- Overall Survival (OS)(two years)
- Duration of Response (DOR)(one year)
- Stable Disease(one year)