UGT1A1 Genotype-drien Phase I Study of Irinotecan in VIT Regimen for the Treatment of Pediatric R/R Solid Tumors

Prior treatment

• Patients who have previously received chemotherapy with irinotecan combined with temozolomide and vincristine, or patients who have progressed after receiving treatment with irinotecan or temozolomide;
• During the study period, patients must not receive any other chemotherapy, radiotherapy, or granulocyte colony-stimulating therapy;
• Patients who have previously undergone organ transplantation;
• Patients requiring high-dose dexamethasone treatment;

Other illness

• Patients positive for hepatitis B surface antigen;
• Patients infected with HIV or syphilis;
• Uncontrolled active systemic bacterial, viral, or fungal infections; Clostridium difficile infection requiring treatment;
• Patients allergic to dacarbazine or cephalosporin drugs;
• Patients with a severe history of neurological or psychiatric disorders, including epilepsy or autism.

Lab values

• Patients receiving P450 enzyme-inducing antiepileptic drugs (antiepileptic drugs affect the clearance of irinotecan);

• Age \< 18 years.
• Relapsed and refractory childhood solid tumors (pathologically confirmed). Definition of relapsed and refractory patients: 1. Patients who fail to achieve GPR or CR after first-line treatment are defined as refractory; 2. Patients who achieve CR after first-line treatment but relapse after more than 1 month are defined as relapsed.
• Must have undergone UGT1A1\*6 genotype testing (provided free of charge by Jiangsu Hengrui Medicine Co., Ltd.), with results being wild type (T/T).
• Patients must be at least 3 weeks post the last myelosuppressive chemotherapy and at least 6 months post hematopoietic stem cell transplantation, 2 weeks post local radiotherapy, 6 months post craniospinal or extensive pelvic radiotherapy, or 6 weeks post extensive bone marrow radiotherapy.
• Must have at least one measurable lesion as defined by RECIST criteria;
• Karnofsky score (for ages \> 10, see Annex I) or Lansky score (for ages ≤ 10, see Annex II) ≥ 50 points;
• Expected survival time ≥ 6 months;
• Patients must have fully recovered from all acute toxic effects of previous anticancer chemotherapy: a) Bone marrow suppression chemotherapy: at least 21 days post the last bone marrow suppressive chemotherapy; b) Hematopoietic growth factors: at least 14 days post the last dose of long-acting growth factor or 7 days post the last dose of short-acting growth factor;
• For patients known not to involve the BM: a) Absolute neutrophil count (ANC) ≥ 1.0×10⁹/L; b) Non-transfused platelet count ≥ 100.0×10⁹/L; c) Hemoglobin ≥ 80 g/L;
• Liver and kidney functions must meet the following criteria: a) Total bilirubin (conjugated + unconjugated) ≤ 1.5× upper limit of normal (ULN) for age; b) Aspartate aminotransferase (AST) ≤ 2.5×ULN (≤ 110 U/L); c) Glomerular filtration rate or creatinine clearance ≥ 70 mL/min/1.73 m² or corresponding age-normal serum creatinine; d) Serum albumin ≥ 20 g/L.
• Capable of adhering to outpatient treatment, laboratory monitoring, and necessary clinical visits during the study period;
• Parents/guardians of children or adolescent subjects must be able to understand, consent to, and sign the informed consent form (ICF) and applicable child consent forms before initiating any protocol-related procedures; if parents/guardians agree, subjects must be capable of expressing consent (when applicable).