Sequential PD-1/PD-L1 Inhibitor and LENvatinib in TLCT and Refractory Hepatoblastoma After Chemotherapy

Study Overview
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Brief Summary
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This is a single arm, open-label trial studying the combination of PD-1/PD-L1 Inhibitor (e.g.pembrolizumab, Sintilimab,Duvarizumab，Camrelizumab )and lenvatinib given at the recommended dose in pediatric and young adolescent patients((5 year-old<age<14 year-old) with TLCT or refractory hepatoblastoma after chemotherapy.

Detailed Description
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Transitional liver cell tumors exhibit an unusual phenotype with respect to clinical presentation, histopathology, immunohistochemistry, and treatment response. These apparently novel, unusual, and aggressive tumors occurring in older children and adolescents may form a transition in the putative developmental pathway of hepatocarcinogenesis, and usually refractory, resistant to chemotherapy. The sPLENTY-pc is a perspective cohort study, investigating the efficiency of sequential combined usage of PD-1 Inhibitor (e.g.pembrolizumab, Sintilimab,Camrelizumab ) or PD-L1 inhibitor (Duvarizumab) plus lenvatinib given at the recommended dose in pediatric >5 year-old and young adult patients<14 yo with TLCT or refractory hepatoblastoma after chemotherapy.

Official Title
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Sequential PD-1/PD-L1 Inhibitor and LENvatinib in Transitional Liver Cell Tumors（TLCT）and Refractory Hepatoblastoma for Young Adolescent and Pediatric Participants After Chemotherapy：a Cohort Study

Conditions
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Transitional Cell Tumor, Hepatoblastoma, Liver Cancer, Pediatric Solid Tumor, Pediatric Cancer

Intervention / Treatment
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* Drug: PD-1 inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be >= than 5 years and =< 14 years of age at the time of study enrollment pathological diagnosis of TLCT/NOS, or hepatoblastoma（HB）（Emergent Treatment for HB In emergency situation when a patient meets all other eligibility criteria and has had baseline required observations, but is too ill to undergo a biopsy safely, the patient may be enrolled without a biopsy.） Failed prior first-line or second-line chemotherapy general charactoristics: Lansky performance status 50-100% in patients ≤ 10 years of age OR Karnofsky performance status 50-100% in patients > 10 years of age Life expectancy > 8 weeks Hemoglobin > 8 g/dL Absolute neutrophil count > 1,000/mm^3 Platelet count > 100,000/mm^3 Total bilirubin ≤ 5 x upper limit of normal (ULN) for age, Aspartate aminotransferase (AST) or Alanine transaminase (ALT) < 10 x upper limit of normal (ULN) for age. Serum creatinine ≤ 3 times normal Normal metabolic parameters (i.e., serum electrolytes, glucose, calcium, and phosphate) Not pregnant or nursing No severe uncontrolled infection or enterocolitis Recovered from toxicity of prior therapy No chemotherapy within 3 weeks prior to study entry No prior PD1/PD-L1 blockade treatment Exclusion Criteria: Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. Patients who are currently receiving another investigational drug. Patients who are currently receiving other anticancer agents. Patients with uncontrolled infection. Current or prior use of immunosuppressive medication within 14 days before the first dose of PD1/PD-L1 blockade

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PLEN(PD-1/PD-L1 inhibitor and LENvatinib)<br>Treatment of PD-1/PD-L1 Inhibitor and LENvatinib would be employed in PLEN | Drug: PD-1 inhibitor<br>* Sequential PD-1/PD-L1 Inhibitor and LENvatinib treatment after chemotherapy resistance<br>* Other names: Sintilimab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (complete response/partial response) | Determined using Response Evaluation Criteria in Solid Tumors version 1.1. A responder is defined as a patient who achieves a best response of partial response or complete response on the study. Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed using the Wilson score interval method. | up to 1 year | 
| dynamic α-fetoprotein response (AFP-R) | The AFP-R was measured as the difference between maximum and final pre-liver transplant/resection AFP level, if surgery is not possible, the final level of AFP would be measured as the AFP at 6 month. | up to 6 months for unresectable. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of study treatment-related adverse events measured by the Common Terminology Criteria for Adverse Events (CTCAE) v. 5 | oxicities will be defined using the Common Terminology Criteria for Adverse Events (CTCAE) v. 5. | up to 12 months | 
| Health outcomes as assessed by the PROMIS® Pediatric Scale v1.0 Global Health 7+2 scores at baseline, prior to start of each cycle, and last trial visit | Each question will be rated from the following: Excellent (5) to Poor (1), Never (5) to Always (1), or Never (1) to Almost Always (5) | up to 12 months |