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

Sponsor
Sun Yat-sen University
Study ID
NCT06760117
Phase
PHASE1
Status
Recruiting
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Conditions

  • Pediatric Solid Tumor

Eligibility Criteria

Sex
ALL
Age
N/A - 18 Years
Healthy Volunteers
Not accepted

Interventions

  • Irinotecan (CPT-11) — DRUG
    Irinotecan will start at a dose of 50mg/m² and escalate to explore the maximum tolerated dose.
  • Temozolomide (TMZ) — DRUG
    TMZ：100mg/m2/d，d1-5
  • Vincristine — DRUG
    VCR: 1.5mg/m2/d(≯2mg), d1

Study Details

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.

Key Dates

Start date
Jan 1, 2022
Status verified
Dec 2024
Primary completion
Jun 30, 2025
Completion
Dec 31, 2025

Study Design

Enrollment
39 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Phase Ia
    A phase Ia dose escalation study of temozolomide and vincristine at fixed doses and escalating doses of irinotecan (patients with wild-type UGT1A1 \*6 (T/T) genotype are eligible for dose escalation of irinotecan) for the treatment of relapsed/refractory pediatric solid tumors. The standard 3+3 patient enrollment design was adopted.
  • Other: Phase Ib
    In the VIT regimen, irinotecan will be administered using the RP2D dose determined by Phase Ia, with an expansion to 9-12 additional patients to further explore efficacy and safety.

Primary Outcome Measure

MTD and DLT [ Time Frame: From the start of the VIT regimen to 16 days after the end of the regimen. ]

Central Contacts

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