Ignite Creation Date:
2024-05-06 @ 7:28 PM
Last Modification Date:
2024-10-26 @ 3:07 PM
Study NCT ID:
NCT06023641
Status:
RECRUITING
Last Update Posted:
2024-05-08
First Post:
2023-08-27
Brief Title:
Treatment of Newly Diagnosed Rhabdomyosarcoma Using Molecular Risk Stratification and Liposomal Irinotecan Based Therapy in Children With Intermediate and High Risk Disease
Sponsor:
St Jude Childrens Research Hospital
Organization:
St Jude Childrens Research Hospital
Study Overview
Official Title:
A Protocol for the Treatment of Newly Diagnosed Rhabdomyosarcoma Using Molecular Risk Stratification and Liposomal Irinotecan Based Therapy in Children With Intermediate and High Risk Disease
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a phase I-II study to determine safety and efficacy of combining liposomal irinotecan with vincristine alternating with VAC in intermediate-risk patients liposomal irinotecan with temozolomide and vincristine alternating with VAC in high-risk patients and the chemotherapy combinations when given with concomitant radiation therapy in intermediate and high risk patients
Primary Objective
The primary objective of the Phase I part is to estimate the maximum tolerated doses MTDs and recommended Phase II doses RP2Ds of combining liposomal irinotecan with vincristine alternating with VAC in intermediate-risk patients liposomal irinotecan with temozolomide and vincristine alternating with VAC in high-risk patients and the chemotherapy combinations when given with concomitant radiation therapy in intermediate and high risk patients
Estimate event-free survival for intermediate-risk participants treated with VAC and vincristine and liposomal irinotecan VLI with the addition of maintenance therapy with vinorelbine and cyclophosphamide
Estimate the event-free survival for high-risk patients treated with VAC and vincristine liposomal irinotecan and temozolomide with the addition of maintenance therapy with vinorelbine and cyclophosphamide
Estimate the local recurrence rate for unresected intermediate- and high-risk patients with initial tumor size with 5 cm randomized to between 594 GyRBE and 68 GyRBE total proton radiation dose while receiving VACVLI intermediate-risk or VACVLI plus temozolomide high-risk and maintenance therapy
Secondary Objectives
To assess the relation between pharmacogenetic variation in CEP72 genotype and vinca alkaloid vincristine vinorelbine disposition in children with rhabdomyosarcoma
To assess the relation between the pharmacogenetic variation in drug metabolizing enzymes and drug transporters and the pharmacokinetics of vinca alkaloids liposomal irinotecan and cyclophosphamide in children with rhabdomyosarcoma
To assess the extent of inter-patient variability in the pharmacokinetics of vinca alkaloids liposomal irinotecan and cyclophosphamide in children with rhabdomyosarcoma and explore possible associations between drug disposition and patient specific covariates eg age sex race weight
Estimate the cumulative incidence of local recurrence in patients with low-risk disease treated with either no adjuvant radiation or minimal volume radiation
Primary Objective
The primary objective of the Phase I part is to estimate the maximum tolerated doses MTDs and recommended Phase II doses RP2Ds of combining liposomal irinotecan with vincristine alternating with VAC in intermediate-risk patients liposomal irinotecan with temozolomide and vincristine alternating with VAC in high-risk patients and the chemotherapy combinations when given with concomitant radiation therapy in intermediate and high risk patients
Estimate event-free survival for intermediate-risk participants treated with VAC and vincristine and liposomal irinotecan VLI with the addition of maintenance therapy with vinorelbine and cyclophosphamide
Estimate the event-free survival for high-risk patients treated with VAC and vincristine liposomal irinotecan and temozolomide with the addition of maintenance therapy with vinorelbine and cyclophosphamide
Estimate the local recurrence rate for unresected intermediate- and high-risk patients with initial tumor size with 5 cm randomized to between 594 GyRBE and 68 GyRBE total proton radiation dose while receiving VACVLI intermediate-risk or VACVLI plus temozolomide high-risk and maintenance therapy
Secondary Objectives
To assess the relation between pharmacogenetic variation in CEP72 genotype and vinca alkaloid vincristine vinorelbine disposition in children with rhabdomyosarcoma
To assess the relation between the pharmacogenetic variation in drug metabolizing enzymes and drug transporters and the pharmacokinetics of vinca alkaloids liposomal irinotecan and cyclophosphamide in children with rhabdomyosarcoma
To assess the extent of inter-patient variability in the pharmacokinetics of vinca alkaloids liposomal irinotecan and cyclophosphamide in children with rhabdomyosarcoma and explore possible associations between drug disposition and patient specific covariates eg age sex race weight
Estimate the cumulative incidence of local recurrence in patients with low-risk disease treated with either no adjuvant radiation or minimal volume radiation
Detailed Description:
This is a phase I-II study to determine safety and efficacy of combining liposomal irinotecan with vincristine alternating with VAC in intermediate-risk patients liposomal irinotecan with temozolomide and vincristine alternating with VAC in high-risk patients and the chemotherapy combinations when given with concomitant radiation therapy in intermediate and high risk patients The phase I part dose-finding phase is a dose-escalation part using the BOIN design with maximally 18 patients for each of groups intermediate -risk high-risk and intermediate -and-high-risk-with-early-radiation Phase I part is to find the maximum tolerated dose and recommended phase II dose for the subsequent phase II part Phase II part has two primary objectives The first objective will derive the sample size and it is for efficacy and the endpoint is defined as a 2-year event-free survival EFS for each stratum with 4 years enrollment and 2 years follow-up for each patient by 80 power and 5 type I error rate a single-arm adaptive phase II design is used to have estimated numbers of patients for intermediate-risk and high-risk groups are 46 and 33 respectively The study will end once the last enrolled patient has been followed by 2 years The second objective is to evaluate the local recurrence rate LRR of patients with tumor size 5cm by using a 21 randomization design of comparing administration of the two radiation strategies 594 GyRBE and 68 GyRBE For this part 27 additional patients will be required
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2024-00701 | OTHER | NCI Clinical Trial Registration Program | None |