Apatinib Mesylate Combined With IT Regimen for the Treatment of Recurrent or Refractory Pediatric Neuroblastoma: A Single-arm, Phase I/II，Multi-center, Clinical Study.

NCT05027386 | Recruiting Phase 1

• 1 other identifier: AIT-NB-01
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 1

Brief Summary

The survival rate of recurrent and refractory pediatric neuroblastoma is low and the prognosis is poor. Apatinib mesylate is a highly selective small-molecule vasoendothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor. Apatinib mesylate has been shown to be safe and effective in recurrent or refractory pediatric neuroblastoma in Sun Yat-sen University Cancer Center. Apatinib mesylate combined with IT regimen is expected to further improve the efficacy and survival rate of recurrent or refractory pediatric neuroblastoma.

Conditions

Neuroblastoma

Keywords

apatinib; irinotecan; temozolomide; neuroblastoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  In the phase I stage, the primary endpoint is RPIID. In the phase II stage, the primary outcome was the objective response rate of apatinib combined with IT in the treatment of recurrent or refractory pediatric neuroblastoma, including complete response (CR) and partial response (PR).

  up to 6 courses of therapy, or about 6 months

Secondary Outcomes (4)

• Progression-free survival

  up to 60 months

• Overall survival

  up to 60 months

• Duration of remission

  up to 60 months

• Disease control rate (DCR)

  up to 6 courses of therapy, or about 36 months

Study Arms (4)

The first dose level

EXPERIMENTAL

The first dose level of apatinib combined with fixed-dose 5-day courses of irinotecan (50 mg/m²/dose infused IV 90 min) plus temozolomide (100 mg/m²/dose infused IV 90 min) for up to six courses.

Drug: Apatinib, Irinotecan, Temozolomide

The second dose level

EXPERIMENTAL

The second dose level of apatinib combined with fixed-dose 5-day courses of irinotecan (50 mg/m²/dose infused IV 90 min) plus temozolomide (100 mg/m²/dose infused IV 90 min) for up to six courses.

Drug: Apatinib, Irinotecan, Temozolomide

The third dose level

EXPERIMENTAL

The third dose level of apatinib combined with fixed-dose 5-day courses of irinotecan (50 mg/m²/dose infused IV 90 min) plus temozolomide (100 mg/m²/dose infused IV 90 min) for up to six courses.

Drug: Apatinib, Irinotecan, Temozolomide

Phase 2: The RPIID group

EXPERIMENTAL

Based on the Phase I stage of apatinib, the recommended phase II dose was administered in combination with the IT regimen every three weeks for up to six cycles, followed by maintenance therapy with apatinib until tumor progression recurrence or unacceptable toxicity.

Drug: Apatinib, Irinotecan, Temozolomide

Interventions

Apatinib, Irinotecan, Temozolomide DRUG

In the Phase I stage, apatinib was administered using a 3+3 dose escalation design with three dose cohorts. The IT regimen was maintained at fixed doses, with patients receiving up to 6 cycles of chemotherapy. The recommended Phase II dose (RP2D) was determined from the Phase I dose-escalation phase. In the Phase II stage, the study included an apatinib combination therapy phase and an apatinib maintenance therapy phase. During the combination therapy phase, apatinib was administered at the RP2D in combination with the IT regimen (at fixed doses) for up to 6 cycles. In the maintenance therapy phase, apatinib was administered orally as a single agent at the RP2D until disease progression or intolerable toxicity occurred.

Also known as: Irinotecan, temozolomide

Phase 2: The RPIID group; The first dose level; The second dose level; The third dose level

Eligibility Criteria

• Age: 5 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• years ≤ age ≤18 years old, regardless of gender;;
• ECOG performance status (PS) score: 0～1;
• The expected survival time is more than 12 weeks;
• Children with neuroblastoma confirmed by histopathology;
• Patients who have progressed, recurrent or refractory disease after first-line treatment (failure to obtain complete or partial remission after recent treatment);
• With measurable lesions (according to the RECIST 1.1 standard, the CT scan of tumor lesions has a long diameter ≥10mm, and the CT scan of lymph node lesions has a short diameter ≥15mm. The measurable lesions have not been treated with radiotherapy or cryotherapy);
• The patients must recover from the acute toxic effects of all previous anticancer chemotherapy fully;
• Myelosuppressive chemotherapy: at least 21 days after the last myelosuppressive chemotherapy (If nitrosourea was used in the early stage, the interval time is 42 days);
• Experimental drugs or anti-cancer therapies other than chemotherapy: It is not allowed to use other experimental drugs within 28 days before the planned start of use, and it is necessary to fully recover from the clinically significant toxicity of the therapy;
• Hematopoietic growth factors: at least 14 days after the last administration of long-acting growth factors or 3 days after the last administration of short-acting growth factors;
• \. Immunotherapy: At least 42 days after completing any type of immunotherapy (except steroids), such as immune checkpoint inhibitors and tumor vaccines;
• \. X-ray therapy (XRT): at least 14 days after local palliative XRT (small-scale mouth); if it is another substantial bone marrow (BM) irradiation, including pre-radio-iodinated metaiodobenformin (131I-MIBG) treatment, the interval time must end at least 42 days;
• Stem cell infusion without total body irradiation (TBI): there is no evidence of active graft-versus-host disease, at least 56 days after transplantation or stem cell infusion;
• Laboratory inspections during the screening period should meet the following conditions: The absolute value of neutrophils (ANC) ≥1.5×109/L (if the bone marrow is invaded, then ANC≥1.0×109/L) Platelet (PLT) ≥75×109/L (if bone marrow invades, then PLT ≥50×109/L) Bilirubin ≤1.5 times ULN Creatinine ≤ 1.5 times ULN (calculated according to the standard Cockcroft-Gault formula) ALT/AST≤3 times ULN (if there is liver metastasis, it can be relaxed to 5 times ULN);
• During the study period, patients should be able to comply with outpatient treatment, laboratory monitoring, and necessary clinical visits;

You may not qualify if:

• Symptomatic brain metastases (patients with brain metastases who have completed treatment 21 days before enrollment and have stable symptoms can be enrolled, but they need to be evaluated by cranial MRI, CT, or venography to confirm that they have no symptoms of cerebral hemorrhage);
• Imaging (CT or MRI) shows that the tumor focus is ≤ 5 mm from large blood vessels, or there is a tumor that invades local large blood vessels;
• Patients with hypertension who are using two or more antihypertensive drugs in combination therapy;
• Patients who suffer from the following cardiovascular diseases: Myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmia (including QTc interval ≥450 ms for males and ≥470 ms for females); according to NYHA standards, grade III to IV cardiac insufficiency, or the heart color Doppler ultrasound examination showed that the left ventricular ejection fraction (LVEF) \<50%;
• Patients with a history of interstitial pulmonary disease or who also suffer from the interstitial pulmonary disease;
• Abnormal coagulation function (INR\>1.5 or prothrombin time (PT)\>ULN+4 seconds or APTT\>1.5 ULN), have a bleeding tendency or are receiving thrombolytic or anticoagulant therapy;
• The daily volume of hemoptysis reached two teaspoons or more before enrollment;
• Patients who have had clinically significant bleeding symptoms or a clear bleeding tendency within 3 months before enrollment, such as gastrointestinal bleeding, hemorrhagic hemorrhoids, hemorrhagic gastric ulcer, fecal occult blood++ and above at baseline, or vascular
• Arterial/venous thrombosis events that occurred in the 12 months before enrollment, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
• Known existing hereditary or acquired bleeding and thrombotic tendency (such as hemophilia, blood coagulation dysfunction, thrombocytopenia, hypersplenism, etc.);
• Long-term unhealed wounds or fractures (pathological fractures caused by tumors are not counted);
• Patients who received major surgery or suffered severe traumatic injury, fracture, or ulcer within 4 weeks of enrollment;
• some factors significantly affect the absorption of oral drugs, such as inability to swallow, chronic diarrhea, and intestinal obstruction;
• Abdominal fistula, gastrointestinal perforation, or abdominal abscess occurred within 6 months before enrollment;
• Urine routine test showed urine protein ≥ ++, and confirmed 24-hour urine protein ≥ 1.0 g; Notes: Asymptomatic serous effusions can be included in the group, and symptomatic serous effusions have been actively treated symptomatically (anti-cancer drugs cannot be used for the treatment of serious effusions), and patients who are judged by the investigator can be included in the group，allow to join the group.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Yizhuo Zhang

Guangzhou, Guangdong, China

RECRUITING

MeSH Terms

Conditions

Neuroblastoma

Interventions

apatinib; Irinotecan; Temozolomide

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)

Camptothecin; Alkaloids; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Yizhuo Zhang

  Sun Yat-Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yizhuo Zhang

CONTACT

020-87342460; zhangyzh@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of department of pediatric cancer,Principal Investigator,Clinical Professor,

Study Record Dates

• First Submitted: August 22, 2021
• First Posted: August 30, 2021
• Study Start: August 26, 2021
• Primary Completion: February 4, 2026
• Study Completion: February 4, 2026
• Last Updated: February 5, 2026

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)