Sequential PD-1/PD-L1 Inhibitor and LENvatinib in TLCT and Refractory Hepatoblastoma After Chemotherapy (sPLENTY-pc)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Pediatric Cancer; Liver Cancer; Hepatoblastoma; Pediatric Solid Tumor; Transitional Cell Tumor
• Intervention / Treatment: Drug: PD-1 inhibitor

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Qiang Xia

Study Locations

• China
  • Shanghai, China, 200127
    • Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PLEN(PD-1/PD-L1 inhibitor and LENvatinib); Treatment of PD-1/PD-L1 Inhibitor and LENvatinib would be employed in PLEN	Drug: PD-1 inhibitor; Sequential PD-1/PD-L1 Inhibitor and LENvatinib treatment after chemotherapy resistance; Other Names: Pembrolizumab; Camrelizumab; Sintilimab; PD-L1 inhibitor; lenvatinib; Duvarizumab

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Investigators: Principal Investigator: Hao Feng, Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTU

Study record dates

Study Major Dates

• Study Start (Anticipated): April 10, 2022
• Primary Completion (Anticipated): September 30, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: April 3, 2022
• First Submitted That Met QC Criteria: April 3, 2022
• First Posted (Actual): April 11, 2022

Study Record Updates

• Last Update Posted (Actual): April 11, 2022
• Last Update Submitted That Met QC Criteria: April 3, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms, Complex and Mixed; Neoplasms; Hepatoblastoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Pembrolizumab; Lenvatinib; Immune Checkpoint Inhibitors
• Other Study ID Numbers: RenJi-IIT2022-241

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No