UGT1A1 Genotype-drien Phase I Study of Irinotecan in VIT Regimen for the Treatment of Pediatric R/R Solid Tumors
Trial Parameters
Brief Summary
Irinotecan is a commonly used salvage chemotherapy drug for children with relapsed and refractory solid tumors. Common dose-limiting toxicities of irinotecan include abdominal pain and diarrhea. Studies have shown that patients with UGT1A16 gene mutations have a higher incidence of these side effects, thereby limiting the dosage of irinotecan. The combination of irinotecan with temozolomide and vincristine is a common salvage chemotherapy regimen for children with relapsed and refractory solid tumors. Currently, the recommended dose of irinotecan is 50mg/m², but there is still significant room for improvement in the efficacy of VIT for these children. Whether patients with wild-type UGT1A16 can further increase the dosage of irinotecan, thereby enhancing the efficacy of the VIT regimen, is the focus of our research.
Eligibility Criteria
Inclusion Criteria: 1. Age \< 18 years. 2. 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. 3. Must have undergone UGT1A1\*6 genotype testing (provided free of charge by Jiangsu Hengrui Medicine Co., Ltd.), with results being wild type (T/T). 4. 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. 5. Must have at least one measurable lesion as defined by RECIST criteria; 6. Karnofsky score (for ages \> 10, see Annex I) or Lansky score (for ages ≤ 10, see Annex II) ≥ 50 po