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

NCT06760117 | Recruiting Phase 1 DMC

• 1 other identifier: Sun Yat-sen University Cancer
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

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.

Conditions

Pediatric Solid Tumor

Keywords

UGT1A1 gene; irinotecan

Outcome Measures

Primary Outcomes (1)

• MTD and DLT

  The maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of irinotecan

  From the start of the VIT regimen to 16 days after the end of the regimen.

Study Arms (2)

Phase Ia

EXPERIMENTAL

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.

Drug: Irinotecan (CPT-11); Drug: Temozolomide (TMZ); Drug: Vincristine

Phase Ib

OTHER

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.

Drug: Irinotecan (CPT-11); Drug: Temozolomide (TMZ); Drug: Vincristine

Interventions

Irinotecan (CPT-11) DRUG

Irinotecan will start at a dose of 50mg/m² and escalate to explore the maximum tolerated dose.

Phase Ia; Phase Ib

Temozolomide (TMZ) DRUG

TMZ：100mg/m2/d，d1-5

Phase Ia; Phase Ib

Vincristine DRUG

VCR: 1.5mg/m2/d(≯2mg), d1

Phase Ia; Phase Ib

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

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

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Interventions

Irinotecan; Temozolomide; Vincristine

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Yizhuo Zhang

  SunYat Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yizhuo Zhang

CONTACT

02087342460; zhangyzh@sysucc.org.cn

Juan Juan

CONTACT

87342460; wangjuan@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: December 29, 2024
• First Posted: January 6, 2025
• Study Start: January 1, 2022
• Primary Completion: June 1, 2025
• Study Completion: December 1, 2025
• Last Updated: January 6, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)