Arsenic Trioxide With MAPK Inhibitors and Chemotherapy for Stage 4/M Neuroblastoma

NCT06933394 | Recruiting Phase 2

• 1 other identifier: SYSKY-2024-749-02
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, single-arm, multi-center clinical trial aims to explore and evaluate the efficacy and safety of the combination therapy involving arsenic trioxide, MAPK inhibitors, and chemotherapy for stage 4/M neuroblastoma.

Conditions

Neuroblastoma

Keywords

neuroblastoma; arsenic trioxide; MAPK inhibitor

Outcome Measures

Primary Outcomes (1)

• Complete remission rate (CRR)

  Complete remission rate

  Four weeks after ATO-combined chemotherapy

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  Four weeks after ATO-combined chemotherapy

• Disease Free Survival

  3 years

• Overall survival

  3 years

• Incidence of Adverse Events

  From the start of the combined regimen until the first documented adverse event, up to 3 years.

Study Arms (1)

Experiment group

EXPERIMENTAL

Drug: Arsenic trioxide; Drug: MAPK inhibitors; Drug: Chemotherapy

Interventions

Arsenic trioxide DRUG

Patients will receive 9 cycles of chemotherapy. ATO dosing: Arsenic trioxide（ATO） is administered 0.18mg/kg per day over eight hours IV daily for ten days. Patients will receive ATO alone on days 1-2 and combined with conventional induction chemotherapy on days 3-10.

Experiment group

MAPK inhibitors DRUG

The dosage of MAPK inhibitors is adjusted based on the specific drug. For example, Trametinib is used as follows: Trametinib will be administered daily from Cycle 5 until the end of induction chemotherapy. Patients start at Dose Level I; if no hematologic toxicity or severe drug-related complications occur after 1 cycle, the dose is escalated to the next level, otherwise, it is maintained. Dose Level I: 0.016 mg/kg/day (\<6 years) or 0.012 mg/kg/day (\>6 years), po. qd. Dose Level II: 0.024 mg/kg/day (\<6 years) or 0.018 mg/kg/day (\>6 years), po. qd. Dose Level III: 0.032 mg/kg/day (\<6 years) or 0.025 mg/kg/day (\>6 years), po. qd. The dosages of other MAPK inhibitors should be modified according to their respective recommended therapeutic guidelines.

Experiment group

Chemotherapy DRUG

The conventional chemotherapy regimens are as follows: Cycles 1, 2, 4, and 6 follow the CAV regimen (cyclophosphamide(1.2g/m2.d, d3-d4), pirarubicin(25mg/m2.d,d3-d5), vincristine(0.022mg/kg.d or 0.67mg/m2.d，d3-d5)). Cycles 3, 5, and 7 follow the PVP regimen (cisplatin(50mg/m2.d, d3-d6), etoposide(200mg/ m2.d, d3-d5)). Cycles 8 and 9 follow the CT regimen (cyclophosphamide(1.2g/m2.d, d3-d4), topotecan(2mg/m2.d, d3-d5)).

Experiment group

Eligibility Criteria

• Age: 18 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients with a pathological diagnosis of neuroblastoma.
• Preoperative staging as INRG M stage or postoperative staging as INSS stage 4 (regardless of risk classification).
• Age ≥18 months and ≤18 years.
• Informed consent obtained from the legal guardian, and signed informed consent form.

You may not qualify if:

• Patients with a history of other tumors who have received chemotherapy and abdominal radiation therapy.
• Severe progressive or persistent heart failure: NYHA heart function class III or IV, or left ventricular ejection fraction (LVEF) \< 50%.
• Severe progressive or persistent renal failure: glomerular filtration rate (GFR) \< 30 ml/(min·1.73 m²) or serum creatinine \> 5 mg/dL (442 μmol/L).
• Severe liver dysfunction: aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≥ 5× upper limit of normal (ULN), or serum total bilirubin ≥ 3× ULN.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (1)

Sun Yat-sen Memorial Hospital

Guangzhou, Guangdong, 510120, China

RECRUITING

MeSH Terms

Conditions

Neuroblastoma

Interventions

Arsenic Trioxide; Drug Therapy

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds; Therapeutics

Central Study Contacts

Yang Li, Professor

CONTACT

86-020-81332456; drliyang@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2025
• First Posted: April 18, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): May 1, 2031
• Study Completion (Estimated): May 1, 2031
• Last Updated: April 18, 2025

Record last verified: 2025-04

Locations

CN (1)