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

Phase 2Not Yet RecruitingNCT07444918

Tianjin Medical University Cancer Institute and Hospital33 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Interventions

Liposomal Irinotecan, Vincristine, Temozolomide, and Optional AnlotinibDRUG

This is a combination chemotherapy regimen for children (3-18 years old) with relapsed or refractory malignant solid tumors. It includes liposomal irinotecan, vincristine, and temozolomide, with optional anlotinib (dose adjusted by body weight: 8mg/day for \<35kg; 12mg/day for ≥35kg). Administration is divided into short-course (liposomal irinotecan on Day 1) and long-course (liposomal irinotecan on Days 1/8/15) subgroups; other drugs follow the same dosing schedule across subgroups. Each treatment cycle lasts 21 days, and adjustments are made based on clinical conditions.

Eligibility

Sex: ALLMin age: 3 YearsMax age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Objective Response Rate (ORR)

Time frame: At Week 6, Week 12, Week 18, and every 6 weeks thereafter until treatment discontinuation (up to approximately 6 months)

Secondary Outcomes

Disease Control Rate (DCR)

Time frame: At Week 6, Week 12, Week 18, and every 6 weeks thereafter until treatment discontinuation (up to approximately 6 months)

Overall Survival (OS)

Time frame: From treatment initiation until death, up to 5 years of follow-up.

Progression-Free Survival (PFS)

Time frame: From treatment initiation until progression/death, up to 5 years of follow-up.

Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame: From first dose of study treatment until 30 days after the last dose (up to approximately 6 months)