Treatment of Newly Diagnosed Rhabdomyosarcoma Using Molecular Risk Stratification and Liposomal Irinotecan Based Therapy in Children With Intermediate and High Risk Disease

Rhabdomyosarcoma Clinical Trial

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

Clinical Trial 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 59.4 GyRBE and 68 GyRBE total proton radiation dose while receiving VAC/VLI (intermediate-risk) or VAC/VLI 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 (e.g., 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.

Clinical Trial 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 2:1 randomization design of comparing administration of the two radiation strategies, 59.4 GyRBE and 68 GyRBE. For this part, 27 additional patients will be required. ;

Related Conditions & MeSH terms

• Rhabdomyosarcoma

• NCT number: NCT06023641
• Study type: Interventional
• Source: St. Jude Children's Research Hospital
• Contact: Alberto Pappo, MD
• Phone: (901) 595-2322
• Email: alberto.pappo@stjude.org
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 13, 2024
• Completion date: October 2037