Tucidinostat Plus Etoposide in the Treatment of Neuroblastoma in Childhood. (CSIIT-Q36)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Neuroblastoma in Children
• Intervention / Treatment: Drug: Tucidinostat and etoposide

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yizhuo Zhang; Phone Number: 020-87342460; Email: zhangyzh@sysucc.org.cn

Study Locations

• China
  • Guangzhou, China
    • Recruiting
    • Sun Yat-sen University
    • Contact: Yizhuo Zhang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 3~18 years old;
2. 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;
3. Histologically confirmed neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines;
4. Patients must have a history of high-risk neuroblastoma, at least one measurable lesions according to the RECIST 1.1;
5. Patients who have progressed, recurrent or refractory disease after first-line treatment;
6. The residual disease biopsy must be done, if patiens who have persistent disease obtain incomplete response after first line treatment;
7. Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study registration；
8. Patients have not received enzyme-induced anticonvulsant therapy;
9. Patients have not received valproic acid within 30 days before admission;
10. 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.
11. Patients' guardians must be willing and able to understand and comply with the protocol for the duration of the study.

Exclusion Criteria:

1. Patients with severe cardiovascular disease;
2. Patients who have previously received organ transplants;
3. Inability to swallow pills;
4. 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;
5. Active HIV, hepatitis B or hepatitis C;
6. Researchers believe that patients are unsuitable for any other situation in this study.

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: Tucidinostat and etoposide	Drug: Tucidinostat and etoposide; Tucidinostat: 3+3 design，14 mg/m2，17.5 mg/m2，23 mg/m2 etoposide: 50mg/m2,

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Yizhuo Zhang
• Investigators: Principal Investigator: Yizhuo Yizhuo, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2022
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: April 13, 2022
• First Submitted That Met QC Criteria: April 20, 2022
• First Posted (Actual): April 21, 2022

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Neuroblastoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Etoposide
• Other Study ID Numbers: CHIDA-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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