Study Title

Evolutionary Inspired Therapy for Newly Diagnosed, Metastatic, Fusion Positive Rhabdomyosarcoma

Summary

This clinical trial will evaluate 4 different strategies of chemotherapy schedules in newly diagnosed participants with metastatic Fusion Positive (alveolar) Rhabdomyosarcoma. The participant and their physician will choose from: Arm A) a first strike therapy, Arm B) a first strike-second strike (maintenance) therapy, Arm C) an adaptively timed therapy, and Arm D) conventional chemotherapy.

Objective

Primary Objectives 1. To evaluate 4 different therapeutic approaches towards improving the 3 year EFS from its current 6% to 35% in metastatic, fusion-positive rhabdomyosarcoma patients. Secondary Objectives 1. To describe the overall survival for patients treated on all 4 therapeutic approaches. 2. To describe the grade 3+ toxicities of the various approaches 3. To build, improve, and then test mathematical models for predicting and tracking responses to therapies towards improved strategies for preventing resistance and identifying potentially better strategies for utilizing different doses, schedules or agents in the management of FPRMS. 4. To evaluate physician and patient preferences for novel approaches to high risk cancer by accrual to conventional, more and less intensive systemic chemotherapy approaches in metastatic FPRMS. 5. To suggest additional biomarkers by quantifying circulating tumor DNA (ptDNA) in patients and determine if ptDNA changes over time in a manner that reflects tumor burden, presence of resistant cancer cells, response to therapy, predicts risk of progression, and informs the mathematical models. 6. To evaluate a set of radiomic biomarkers calculated from baseline and post-therapy CT and MRI scans, and compare results with treatment response and mathematical model predictions. 7. To perform single cell sequencing of circulating tumor cells to evaluate changes over time. 8. To compare the number of chemotherapy cycles delivered across all treatment arms. 9. To examine parent and patient experiences with treatment decision-making in the setting of multiple therapeutic options and a poor prognosis.