Evolutionary Therapy for Rhabdomyosarcoma

Inclusion Criteria:

• Participants must have a new histologic diagnosis of rhabdomyosarcoma

• Participants must have FISH, PCR or other molecular confirmation of PAX/FOXO1 fusionper institutional standards

• Participants must have sufficient tissue (up to 10 unstained FFPE) for correlativetesting

• All participants must have distant metastatic disease; either biopsy positive or PETavid extranodal or distant nodal lesions determined by the investigator to bemetastatic disease. Patients with a single distant metastatic site that has beenexcised prior to study entry are eligible

• No prior systemic chemotherapy

• Participants enrolled to Arm B, maintenance, must be able to take oralcyclophosphamide. Note: enteral administration of cyclophosphamide is allowable.

• Males and females of reproductive potential may not participate unless they haveagreed to the use of, at minimum, two methods of contraception during and aftertreatment or abstinence.

• Women of childbearing potential should adhere to contraception for a period of 4months after completion of systematic chemotherapy administration

• Men who are sexually active with women of child bearing potential should adhere tocontraception for a period of 4 months after completion of systematic chemotherapyadministration

• All patients and/or their parents or legal guardians must have the ability tounderstand and the willingness to sign a written informed consent or assentdocument.

Exclusion Criteria:

• Participants with regional lymph nodes as the only site of disease are not eligible.Distant nodal sites alone are eligible

• Participants who are receiving any other investigational agents for rhabdomyosarcomaare ineligible

• Participants must not be receiving any additional medicines being given for thespecific purpose of treating cancer. Alternative medications including, but notlimited to cannabis based products would not be a reason for exclusion

• Participants are ineligible if they have uncontrolled intercurrent illnessincluding, but not limited to:

• ongoing or active infection not expected to resolve with current antibioticplan

• cardiac arrhythmia

• psychiatric illness/social situations that would limit compliance with studyrequirements

• Patients who are pregnant or breastfeeding are not eligible because there is noavailable information regarding human fetal or teratogenic toxicities. Females ofchildbearing potential must have a negative serum or urine pregnancy test within 24hours of starting protocol therapy.

• Participants who are considered unable to comply with the safety monitoringrequirements of the study are not eligible