Phase I Study of Irinotecan Dose Adjustment Guided by UGT1A1*6 Genotype in VIT Regimen for the Treatment of Relapsed and Refractory Childhood Solid Tumors

What this Trial Is About

Researchers are studying children with relapsed and refractory solid tumors who have the wild-type UGT1A1 gene to evaluate whether increasing the dose of irinotecan in combination with temozolomide and vincristine (VIT regimen) can improve treatment outcomes. Irinotecan is a commonly used chemotherapy drug, but its dose is often limited by side effects like abdominal pain and diarrhea, especially in patients with certain gene mutations. This trial aims to find the maximum tolerated dose and safety of escalating irinotecan doses to enhance the effectiveness of the VIT regimen for these children. The study begins with fixed doses of temozolomide and vincristine, while irinotecan starts at 50 mg/m² and is gradually increased through five dose groups up to 110 mg/m². Initially, a phase Ia dose escalation phase uses a standard 3+3 design to determine the maximum tolerated dose of irinotecan for patients with the specific wild-type UGT1A1*6 genotype. Following this, a phase Ib expansion will give the recommended irinotecan dose to an additional 9-12 patients to further assess safety and efficacy. Participants will be monitored closely from the start of the VIT regimen until 16 days after its completion to assess dose-limiting toxicities and maximum tolerated dose. Evaluations include measuring tumor response rates, disease control, progression-free survival, and overall survival. Throughout the study, children must adhere to outpatient treatment schedules, clinical visits, and laboratory monitoring. The trial's findings will help guide future advanced clinical studies for this patient group.

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