A Randomized Phase 3 Study of Vincristine, Dactinomycin, Cyclophosphamide (VAC) Alternating with Vincristine and Irinotecan (VI) Versus VAC/VI Plus Temsirolimus (TORI, Torisel, NSC# 683864) in Patients with Intermediate Risk (IR) Rhabdomyosarcoma (RMS).

This randomized phase III trial studies how well combination chemotherapy (vincristine sulfate, dactinomycin, cyclophosphamide alternated with vincristine sulfate and irinotecan hydrochloride or vinorelbine) works compared to combination chemotherapy plus temsirolimus in treating patients with rhabdomyosarcoma (cancer that forms in the soft tissues, such as muscle), and has an intermediate chance of coming back after treatment (intermediate risk).

Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Combination chemotherapy and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether combination chemotherapy or combination chemotherapy plus temsirolimus is more effective in treating patients with intermediate-risk rhabdomyosarcoma.

Eligibility

• Ages up to 40 years old
• Feasibility Phase: Patients must be < 21 years of age at the time of enrollment; please note: the feasibility phase is complete
• Efficacy Phase: Patients must be =< 40 years of age at the time of enrollment
• Patients with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based upon institutional histopathologic classification, are eligible to enroll on the study based upon stage, group, and age, as below
• RMS types included under embryonal rhabdomyosarcoma (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 2013 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); classification of alveolar rhabdomyosarcoma (ARMS) in the 2013 WHO classification is the same as in the ICR and includes classic and solid variants

- ERMS
- Stage 1, group III (non-orbit)
- Stage 3, group I/II
- Stage 2/3, group III

• - Stage 4, group IV, < 10 years old - ARMS: - Stages 1-3, groups I-III Specimen Submission: Patients must have sufficient tissue available for the required biology studies Lansky performance status score >= 50 for patients == 50 for patients > 16 years of age
• Peripheral absolute neutrophil count (ANC) >= 750/uL
• Platelet count >= 75,000/uL
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

- 1 month to < 6 months old: 0.4 mg/dl (male), 0.4 mg/dl (female)
- 6 months to < 1 year old: 0.5 mg/dl (male), 0.5 mg/dl (female)
- 1 to < 2 years old: 0.6 mg/dl (male), 0.6 mg/dl (female)
- 2 to < 6 years old: 0.8 mg/dl (male), 0.8 mg/dl (female)
- 6 to < 10 years old: 1 mg/dl (male), 1 mg/dl (female)
- 10 to < 13 years old: 1.2 mg/dl (male), 1.2 mg/dl (female)
- 13 to < 16 years old: 1.5 mg/dl (male), 1.4 mg/dl (female) - >= 16 years old: 1.7 mg/dl (male), 1.4 mg/dl (female)

• Patients with an elevated serum creatinine due to obstructive hydronephrosis secondary to tumor are still eligible; however, patients with urinary tract obstruction by tumor must have unimpeded urinary flow established via diversion (ie. percutaneous nephrostomies or ureteric stents) of the urinary tract
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
• 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

Contact

For additional study information, please contact Ashley Bayne:

• Phone: 352-294-8745
• Email: abayne@ufl.edu