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

NCT05027386 | Completed 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 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 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 neuroblastoma, including complete response (CR) and partial response (PR).

  up to 8 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 8 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 (150 mg/m²/dose infused IV 90 min) for up to 8 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 (150 mg/m²/dose infused IV 90 min) for up to 8 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 (150 mg/m²/dose infused IV 90 min) for up to 8 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 8 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 8 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 8 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: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥2 years (for patients enrolled in Phase 1, age \<18 years); no gender restriction.
• Karnofsky Performance Status (KPS) score ≥50 for patients aged ≥16 years, or Lansky Performance Status (LPS) score ≥50 for patients aged \<16 years (see Appendix 1).
• Estimated life expectancy of at least 12 weeks.
• Histologically confirmed diagnosis of neuroblastoma meeting clinical diagnostic criteria.
• Disease progression, recurrence, or treatment resistance (failure to achieve CR or PR following the most recent therapy) after first-line treatment.
• Measurable or evaluable disease (per INRC criteria; see Appendix 3; target lesions must not have received prior local treatment such as radiotherapy or cryotherapy).
• Complete recovery from all acute toxic effects of prior anticancer chemotherapy.
• Myelosuppressive chemotherapy: at least 21 days since the last myelosuppressive chemotherapy regimen (or 42 days if nitrosoureas were administered).
• Investigational agents or anticancer therapies other than chemotherapy: must not have been administered within 28 days prior to the planned initiation of the AIT regimen. Complete recovery from any clinically significant toxicity associated with such therapy must be confirmed.
• Hematopoietic growth factors: at least 14 days since the last administration of long-acting growth factors, or at least 3 days since the last administration of short-acting growth factors.
• Immunotherapy: at least 42 days since completion of any type of immunotherapy (excluding corticosteroids), such as immune checkpoint inhibitors or tumor vaccines.
• Radiotherapy (XRT): at least 14 days since localized palliative XRT (small-field irradiation); for other substantial bone marrow irradiation, including prior ¹³¹I-metaiodobenzylguanidine (¹³¹I-MIBG) therapy, a minimum interval of 42 days is required.
• Stem cell infusion without total body irradiation: no evidence of active graft-versus-host disease, and at least 56 days since transplantation or stem cell infusion.
• Laboratory tests during the screening period must meet the following criteria:
• (1)Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L (≥1.0 × 10⁹/L if bone marrow involvement is present) (2)Platelet count (PLT) ≥75 × 10⁹/L (≥50 × 10⁹/L if bone marrow involvement is present) (3)Total bilirubin ≤1.5 × upper limit of normal (ULN) (4)Serum creatinine ≤1.5 × ULN (5)Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤3 × ULN (may be ≤5 × ULN in the presence of liver metastases) 15.Ability to comply with outpatient treatment, laboratory monitoring, and required clinical visits during study participation.

You may not qualify if:

• Symptomatic brain metastases (patients with brain metastases who have completed treatment within 21 days prior to enrolment and have stable symptoms may be enrolled, provided that cranial magnetic resonance imaging \[MRI\], computed tomography \[CT\], or venography confirms the absence of cerebral haemorrhage).
• Imaging (CT or MRI) demonstrating that the tumour lesion is located ≤5 mm from a major blood vessel, or that the tumour invades a local major blood vessel.
• Hypertension currently requiring treatment with two or more antihypertensive medications.
• Prior or concurrent clinically significant cardiovascular disease, including congenital heart disease, pericardial disease, history of heart failure, myocardial infarction, coronary artery disease, valvular heart disease, cardiomyopathy, or arrhythmias (including persistent atrial fibrillation, complete left bundle branch block, or frequent premature ventricular contractions); corrected QT interval (QTc) \>480 ms; New York Heart Association (NYHA) Class III-IV cardiac dysfunction for patients aged \>3 years or corresponding criteria for infantile cardiac function for patients aged ≤3 years (see Appendix 2); or echocardiography demonstrating left ventricular ejection fraction (LVEF) \<50%.
• History of or concurrent interstitial lung disease.
• Abnormal coagulation function (international normalised ratio \[INR\] \>1.5, prothrombin time \[PT\] \>ULN + 4 seconds, or activated partial thromboplastin time \[APTT\] \>1.5 × ULN), bleeding tendency, or ongoing thrombolytic or anticoagulant therapy.
• Haemoptysis of ≥2 teaspoons daily prior to enrolment.
• Clinically significant bleeding symptoms or clear bleeding tendency within the preceding 3 months, such as gastrointestinal bleeding, haemorrhagic haemorrhoids, haemorrhagic gastric ulcer, baseline faecal occult blood ≥++, or vasculitis.
• Arterial or venous thromboembolic events within 12 months prior to enrolment, including cerebrovascular accident (transient ischaemic attack, cerebral haemorrhage, or cerebral infarction), deep vein thrombosis, or pulmonary embolism.
• Known hereditary or acquired bleeding or thrombotic tendency (e.g., haemophilia, coagulation disorders, thrombocytopenia, or hypersplenism).
• Chronic non-healing wounds or fractures (excluding pathological fractures caused by tumours).
• Major surgical procedure, severe traumatic injury, fracture, or ulcer within 4 weeks prior to enrolment.
• Factors that significantly affect absorption of oral medications, such as inability to swallow, chronic diarrhoea, or intestinal obstruction.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to enrolment.
• Urinalysis showing urinary protein ≥++, with confirmed 24-hour urinary protein excretion ≥1.0 g.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Yizhuo Zhang

Guangzhou, Guangdong, China

Location

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

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: September 10, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)