Tucidinostat Plus Etoposide in the Treatment of Neuroblastoma in Childhood.

Study Overview
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Brief Summary
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Neuroblastoma is a malignant tumor that develops in infants and kids. Dysregulation of histone acetylation is associated with a series of malignant tumors. Neuroblastoma is caused by defective neural crest differentiation due to abnormal gene regulation.

Official Title
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Tucidinostat Plus Etoposide in the Treatment of Relapsed or Refractory Neuroblastoma in Children

Conditions
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Neuroblastoma in Children

Intervention / Treatment
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* Drug: Tucidinostat and etoposide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 3 18 years old; Patients must have a life expectancy of at least 6 weeks and a Lansky (≤16 years) or Karnofsky (>16 years) score of at least 50; Histologically confirmed neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines; Patients must have a history of high-risk neuroblastoma, at least one measurable lesions according to the RECIST 1.1; Patients who have progressed, recurrent or refractory disease after first-line treatment; The residual disease biopsy must be done, if patiens who have persistent disease obtain incomplete response after first line treatment; Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study registration； Patients have not received enzyme-induced anticonvulsant therapy; Patients have not received valproic acid within 30 days before admission; ANC ≥ 1.5×10^9/L, PLT ≥75×10^9/L;TBIL≤1.5ULN, ALT and AST≤3×ULN（ALT and AST≤5×ULN if liver metastasis）;BUN and Cr≤1.5×ULN 9）LVEF ≥ 50% and QTc≤470 ms. Patients' guardians must be willing and able to understand and comply with the protocol for the duration of the study. Exclusion Criteria: Patients with severe cardiovascular disease; Patients who have previously received organ transplants; Inability to swallow pills; Female patients during pregnancy and lactation, fertile women with positive baseline pregnancy tests or women of childbearing age who are unwilling to take effective contraceptive measures throughout the trial; Active HIV, hepatitis B or hepatitis C; Researchers believe that patients are unsuitable for any other situation in this study.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 18 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: Tucidinostat and etoposide<br> | Drug: Tucidinostat and etoposide<br>* Tucidinostat: 3+3 design，14 mg/m2，17.5 mg/m2，23 mg/m2 etoposide: 50mg/m2,<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicity (DLT) | Dose-limiting toxicity defined as any Grade 4 hematological toxicity and any > Grade 3 non-hematologic toxicity. | 1 year | 
| Maximum Tolerated Dose (MTD) | Maximum tolerated dose is highest dose level in which 6 patients treated with at most 1 experiencing DLT. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate(ORR) | Objective Response Rate（ORR）by RECIST 1.1,the total proportion of patients with complete response（CR）, partial response（PR） | 2 years | 
| progression-free survival (PFS) | Time from treatment until disease progression or death | 2 years | 
| overall survival (OS) | Time from treatment until death from any cause | 2 years | 
| disease control rate (DCR) | The total proportion of patients with complete response（CR）, partial response（PR）and Stable Disease（SD） | 2 years |