Pediatric Solid TumorPhase 1NCT06760117
UGT1A1 Genotype-drien Phase I Study of Irinotecan in VIT Regimen for the Treatment of Pediatric R/R Solid Tumors
A Phase 1 study testing Irinotecan (CPT-11), Temozolomide (TMZ) and Vincristine in people with Pediatric Solid Tumor, run by Sun Yat-sen University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Pediatric Solid Tumor
- What is being tested?
- Irinotecan (CPT-11), Temozolomide (TMZ) and Vincristine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2022to Dec 2025
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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;
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- 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).
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 510060
Yi-Zhuo Zhang, 08602087342460, zhangyzh@sysucc.org.cn
About this study
Official title: 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
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.
Read the detailed description
Children with relapsed and refractory solid tumors and wild-type UGT1A1 gene are enrolled in this study. The doses of temozolomide and vincristine are fixed, while irinotecan in the VIT regimen begins at a starting dose of 50mg/m² and escalates across five dosage groups, with the highest dose group being 110mg/m². This study aims to determine the maximum tolerated dose of irinotecan and the safety of incremental irinotecan dosing, as well as the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). This will lay the foundation for future Phase II/III clinical studies.
- Conditions
- Pediatric Solid Tumor
- Being tested
- Irinotecan (CPT-11), Temozolomide (TMZ), Vincristine
- Keywords
- UGT1A1 gene, irinotecan
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
VincristineDrug
VCR: 1.5mg/m2/d(≯2mg), d1
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Irinotecan (CPT-11); Drug: Temozolomide (TMZ); Drug: Vincristine |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD and DLT
The maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of irinotecan
Measured: From the start of the VIT regimen to 16 days after the end of the regimen.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2025
- Study start1 Jan 2022
- Primary completionJun 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pediatric Solid TumorStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 39 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yizhuo Zhang, Sun Yat-sen University
- Investigators
- Yizhuo Zhang, Principal investigator, SunYat Sen University Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06760117
- Sponsor's protocol ID
- Sun Yat-sen University Cancer
- Status last verified
- Dec 2024
- First submitted
- 29 Dec 2024
- Last updated
- 6 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06760117
- Acronym / sponsor ID
- Sun Yat-sen University Cancer
- Conditions
- Pediatric Solid Tumor
- Keywords
- UGT1A1 gene, irinotecan
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 39 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 1 Jan 2022 (actual)
- Primary completion
- Jun 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 6 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Children with relapsed and refractory solid tumors and wild-type UGT1A1 gene are enrolled in this study. The doses of temozolomide and vincristine are fixed, while irinotecan in the VIT regimen begins at a starting dose of 50mg/m² and escalates across five dosage groups, with the highest dose group being 110mg/m². This study aims to determine the maximum tolerated dose of irinotecan and the safety of incremental irinotecan dosing, as well as the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). This will lay the foundation for future Phase II/III clinical studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase Ia | Experimental | Drug: Irinotecan (CPT-11), Drug: Temozolomide (TMZ), Drug: VincristineA 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. |
| Phase Ib | Other | Drug: Irinotecan (CPT-11), Drug: Temozolomide (TMZ), Drug: VincristineIn 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. |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- 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;
Key exclusion criteria (10 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Irinotecan (CPT-11)Irinotecan will start at a dose of 50mg/m² and escalate to explore the maximum tolerated dose. | Drug | Phase Ia, Phase Ib |
| Temozolomide (TMZ)TMZ：100mg/m2/d，d1-5 | Drug | Phase Ia, Phase Ib |
| VincristineVCR: 1.5mg/m2/d(≯2mg), d1 | Drug | Phase Ia, Phase Ib |
Primary outcome
MTD and DLT
Time frame: From the start of the VIT regimen to 16 days after the end of the regimen.
The maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of irinotecan
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yizhuo Zhang principal investigator
SunYat Sen University Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Irinotecan (CPT-11), Temozolomide (TMZ) and Vincristine in people with Pediatric Solid Tumor, run by Sun Yat-sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yizhuo Zhang (02087342460, zhangyzh@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MTD and DLT (time frame: From the start of the VIT regimen to 16 days after the end of the regimen.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2025.