ARST1431, 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, IND# 122782) in Patients with Intermediate Risk (IR) Rhabdomyosarcoma (RMS)

Provide the rationale for the study, including a summary of the background research that has led to your hypothesis/objectives. Rhabdomyosarcoma is the most common soft tissue sarcoma in children and adolescents with approximately 350 new diagnoses annually in the united States. Despite cooperative group trial efforts, about 25% of patients with iR eRMS tumors and 50% of those with iR aRMS tumors will experience disease recurrence and only a small fraction of the patients who relapse can be cured. Temsirolimus is an experimental anticancer drug that has not been approved by the Food and Drug administration (FDa) for use in treating intermediate risk RMS. Temsirolimus has been approved by the FDa since March 2007 for adults with renal cell carcinoma, the most common form of kidney cancer in adults. in laboratory studies temsirolimus has been shown to work in some childhood cancers, including RMS. Temsirolimus has also been combined with chemotherapy and used to treat children whose RMS has come back (relapsed).Temsirolimus has been well-tolerated in children and adults with cancer. But it has not been given along with VaC/Vi therapy to people with intermediate risk RMS who have just been diagnosed. Version Date 04/24/14 Page 3 of 17 For patients found to be low risk, low risk subjects have a tumor in a favorable location that can or has been removed and the tumor lacks a genetic marker called FoXo1, this study is being done to find out the most effective treatment with the least amount of therapy that will still cure patients with low risk RMS. We want to know this because, although chemotherapy and radiation therapy can cure low risk RMS, they can also have effects on patients later in life (late effects). Late effects can include slowing of growth in children, inability to have children (sterility), and causing another cancer to develop.