This is a phase 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
* 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.
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 and overall 3-year event-free survival in patients with low-risk disease, intermediate-risk disease or high-risk disease treated with either no adjuvant radiation or minimal volume radiation and compare these outcomes with the outcomes achieved on RMS13.
Low-risk: TP53 and MYOD1 negative AND
Stage 1 Group I, Group II
Stage 1 Group III orbital only
Stage 2 Group I, Group II
Ongoing or history of non-infectious interstitial lung disease requiring significant medical intervention.
Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for at least 3 months after treatment is completed.
Female patients who are pregnant are not eligible since fetal toxicities or teratogenic effects have been noted for several of the study drugs. Female participants > 10 years of age or post-menarchal must have a negative serum or urine pregnancy test within 24 hours prior to beginning treatment.
Lactating females who are or plan to breastfeed their infants are not eligible.