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

Sponsor

RenJi Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05322187

Collaborator

(none)

Enrollment

Location

Arm

20.7

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Transitional Cell Tumor Hepatoblastoma Liver Cancer Pediatric Solid Tumor Pediatric Cancer	Drug: PD-1 inhibitor	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Apr 10, 2022

Anticipated Primary Completion Date :

Sep 30, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

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: PD-L1 inhibitor lenvatinib Camrelizumab Pembrolizumab Duvarizumab Sintilimab

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:

PD-L1 inhibitor

lenvatinib

Camrelizumab

Pembrolizumab

Duvarizumab

Sintilimab

Outcome Measures

Primary Outcome Measures

Objective response rate (complete response/partial response) [up to 1 year]
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.
dynamic α-fetoprotein response (AFP-R) [up to 6 months for unresectable.]
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.

Secondary Outcome Measures

Incidence and severity of study treatment-related adverse events measured by the Common Terminology Criteria for Adverse Events (CTCAE) v. 5 [up to 12 months]
oxicities will be defined using the Common Terminology Criteria for Adverse Events (CTCAE) v. 5.
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 [up to 12 months]
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

5 Years to 14 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University	Shanghai		China	200127

Sponsors and Collaborators

RenJi Hospital

Investigators

Principal Investigator: Hao Feng, Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTU
Study Chair: Qiang Xia, Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTU