Liposomal Irinotecan, Vincristine, Temozolomide, and Anlotinib for R/R Pediatric Solid Tumors

A Prospective, Single-Center, Single-Arm Study to Evaluate the Efficacy and Safety of Liposomal Irinotecan, Vincristine, and Temozolomide With or Without Anlotinib in Children and Adolescents With Relapsed or Refractory Malignant Solid Tumors

This is a prospective, single-center, single-arm interventional trial conducted at Tianjin Medical University Cancer Institute and Hospital. It evaluates the efficacy and safety of a combination regimen (liposomal irinotecan + vincristine + temozolomide ± anlotinib) in children with relapsed or refractory malignant solid tumors, with the goal of optimizing regimen-related adverse reactions and exploring appropriate administration strategies.

1. Study Objectives Primary Objective: Assess the objective response rate (ORR) of the combination regimen in the study population.

   Secondary Objectives: Evaluate survival outcomes (progression-free survival [PFS], overall survival [OS]) and the incidence of adverse events (per NCI CTCAE v5.0).

2. Eligibility Criteria Inclusion Criteria Aged 3-18 years (inclusive) at consent; Pathologically confirmed relapsed or refractory malignant solid tumors (e.g., neuroblastoma, rhabdomyosarcoma); At least one measurable lesion (per RECIST v1.1); Adequate functional status and organ function (per institutional standards); Written informed consent from subject/legal guardian. Exclusion Criteria Hypersensitivity to study drugs; Active uncontrolled infection or severe comorbidities; Concurrent participation in other interventional trials; Conditions precluding study participation (per investigator judgment).

3. Intervention Procedures

   Eligible subjects are assigned to short-course or long-course subgroups based on clinical status:

   Short-course: Liposomal irinotecan (Day 1), vincristine (Day 1), temozolomide (Days 1-5), ± weight-based anlotinib (Days 1-14); Long-course: Liposomal irinotecan (Days 1/8/15), plus the same doses of other drugs as the short-course subgroup.

   Each treatment cycle is 21 days. Efficacy is assessed regularly; treatment (dose/subgroup) will be adjusted per clinical condition.

4. Outcome Assessments Primary Outcome: ORR (assessed per RECIST v1.1 at regular intervals); Secondary Outcomes: PFS, OS (long-term follow-up post-treatment), and adverse event incidence.

5. Participant Requirements Participation is voluntary. Subjects/guardians must provide written informed consent prior to enrollment. Long-term follow-up will be conducted post-treatment.

Inclusion Criteria:

• Aged 3 to 18 years (inclusive) at the time of informed consent signing.
• Pathologically confirmed relapsed or refractory malignant solid tumors (including but not limited to neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, osteosarcoma).
• At least one measurable lesion (as defined by RECIST v1.1) confirmed by CT/MRI within 28 days prior to enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
• Adequate organ function (absolute neutrophil count ≥1.5×10⁹/L; platelet count ≥100×10⁹/L; hemoglobin ≥90g/L; serum creatinine ≤1.5×upper limit of normal [ULN] for age; total bilirubin ≤1.5×ULN; alanine aminotransferase/aspartate aminotransferase ≤2.5×ULN, or ≤5×ULN if liver metastasis exists).
• Written informed consent provided by the subject (if ≥18 years old) or legal guardian (if <18 years old).

Exclusion Criteria:

• Known hypersensitivity to any component of the study drugs (liposomal irinotecan, vincristine, temozolomide, anlotinib).
• Active systemic infection requiring systemic antibiotic treatment within 7 days prior to enrollment.
• History of severe cardiovascular disease (e.g., congestive heart failure, uncontrolled arrhythmia).
• Concurrent participation in another interventional clinical trial.
• Pregnancy, lactation, or unwillingness to use effective contraception (for sexually active subjects).
• Other medical conditions that, in the investigator's judgment, may affect study participation or outcome assessment.