Using irinotecan to treat children with relapsed solid tumors based on their UGT1A1 gene

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

This study is testing if a combination of irinotecan, temozolomide, and vincristine can help children with relapsed solid tumors who have a specific gene type feel better and live longer.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 39 (estimated)
• Ages: N/A to 18 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06760117 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of irinotecan in combination with temozolomide and vincristine for children with relapsed and refractory solid tumors who have a wild-type UGT1A1 gene. The study starts with a dose of 50mg/m² of irinotecan and escalates to a maximum of 110mg/m² to determine the maximum tolerated dose and evaluate safety. The trial will assess the objective response rate, disease control rate, progression-free survival, and overall survival to inform future studies. The goal is to enhance the efficacy of the VIT regimen for these pediatric patients.

Who should consider this trial

Good fit: Ideal candidates are children under 18 years old with relapsed or refractory solid tumors and wild-type UGT1A1 gene.

Not a fit: Patients with UGT1A1 gene mutations or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment outcomes for children with relapsed solid tumors by allowing higher doses of irinotecan.

How similar studies have performed: Other studies have shown promise in using genotype-driven dosing strategies, but this specific approach is novel.

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 points;
7. Expected survival time ≥ 6 months;
8. 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;
9. 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;
10. 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.
11. Capable of adhering to outpatient treatment, laboratory monitoring, and necessary clinical visits during the study period;
12. 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).

Exclusion Criteria:

1. 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;
2. Patients receiving P450 enzyme-inducing antiepileptic drugs (antiepileptic drugs affect the clearance of irinotecan);
3. During the study period, patients must not receive any other chemotherapy, radiotherapy, or granulocyte colony-stimulating therapy;
4. Patients positive for hepatitis B surface antigen;
5. Patients infected with HIV or syphilis;
6. Patients who have previously undergone organ transplantation;
7. Uncontrolled active systemic bacterial, viral, or fungal infections; Clostridium difficile infection requiring treatment;
8. Patients allergic to dacarbazine or cephalosporin drugs;
9. Patients requiring high-dose dexamethasone treatment;
10. Patients with a severe history of neurological or psychiatric disorders, including epilepsy or autism.

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Yizhuo Zhang — SunYat Sen University Cancer Center
• Study coordinator: Yizhuo Zhang

Conditions Pediatric Solid Tumor; UGT1A1 gene; irinotecan