Inclusion Criteria:

- All patients must be enrolled on APEC14B1 (NCT02402244) and consented to the Molecular
Characterization Initiative (Part A) prior to enrollment and treatment on ARST2032
(this trial).

- Patients must be ≤ 21 years at the time of enrollment.

- Patients must have newly diagnosed embryonal rhabdomyosarcoma (ERMS), spindle
cell/sclerosing RMS, or FOXO1 fusion negative alveolar rhabdomyosarcoma (ARMS)
(institutional FOXO1 fusion results are acceptable). RMS types included under ERMS
include those classified in the 1995 International Classification of Rhabdomyosarcoma
(ICR) as ERMS (classic, spindle cell, and botryoid variants), which are reclassified
in the 2020 World Health Organization (WHO) classification as ERMS (classic, dense and
botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical
spindle cell ERMS variant and the newly recognized sclerosing RMS variant). Enrollment
in APEC14B1 is required for all patients.

- All patients will be evaluated for stage and clinical group. Note that clinical
group designation assigned at the time of enrollment on study remains unchanged
regardless of any second-look operation that may be performed.

- Patients will be eligible for the very low-risk stratum (Regimen VA) if they
have Stage 1, CG I disease.

- Patients will be eligible for the low-risk stratum (Regimen VAC/VA) if they
have Stage 1, CG II disease, Stage 2, CG I or II disease, or Stage 1, CG III
(orbit only) disease.

- Paratesticular Tumors: Staging ipsilateral retroperitoneal lymph node sampling
(SIRLNS) is required for all patients ≥ 10 years of age with paratesticular
tumors who do not have gross nodal involvement on imaging.

- Extremity Tumors: Regional lymph node sampling is required for histologic
evaluation in patients with extremity tumors.

- Clinically or radiographically enlarged nodes must be sampled for histologic
evaluation.

- Patients must have a Lansky (for patients ≤ 16 years of age) or Karnofsky (for
patients > 16 years of age) performance status score of ≥ 50. Patients who are unable
to walk because of paralysis, but who are up in a wheelchair, will be considered
ambulatory for the purpose of assessing performance score.

- Peripheral absolute neutrophil count (ANC) ≥ 750/uL (within 7 days prior to
enrollment).

- Platelet count ≥ 75,000/uL (transfusion independent) (within 7 days prior to
enrollment).

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70
mL/min/1.73 m^2 or a serum creatinine (within 7 days prior to enrollment) based on
age/gender as follows:

- Age: 1 month to < 6 months; Maximum serum creatinine (mg/dL): 0.4 (male) : 0.4
(female);

- Age: 6 months to < 1 year; Maximum serum creatinine (mg/dL): 0.5 (male) : 0.5
(female);

- Age: 1 to < 2 years; Maximum serum creatinine (mg/dL): 0.6 (male) : 0.6 (female);

- Age: 2 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 (male) : 0.8 (female);

- Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 (male) : 1 (female);

- Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 (male) : 1.2
(female);

- Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 (male) : 1.4
(female);

- Age ≥ 16 years; Maximum serum creatinine (mg/dL): 1.7 (male) : 1.4 (female);

- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment); and

- If there is evidence of biliary obstruction by the tumor, then the total
bilirubin must be < 3 x ULN for age.

- Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
value of 45 U/L.

- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
U/L (within 7 days prior to enrollment).

- All patients and/or their parents or legal guardians must sign a written informed
consent.

- All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met.

Exclusion Criteria:

- Patients who have received prior chemotherapy and/or radiation therapy for cancer
prior to enrollment. Surgical resection alone of previous cancer(s) is permitted.

- Patients who have received chemotherapy or radiation for non-malignant conditions
(e.g., autoimmune diseases) are eligible. Patients must discontinue chemotherapy for
non-malignant conditions prior to starting protocol therapy.

- Vincristine is sensitive substrate of the CYP450 3A4 isozyme. Patients must not have
received drugs that are moderate to strong CYP3A4 inhibitors and inducers within 7
days prior to study enrollment.

- Patients unable to undergo radiation therapy, if necessary, as specified in the
protocol.

- Evidence of uncontrolled infection.

- Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs. A pregnancy test is required for female
patients of childbearing potential.

- Lactating females who plan to breastfeed their infants.

- Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 9/9/22. Questions regarding updates should be directed to the study team contact.