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)
Clinical Trial Information
Trial Contact: El-Shami, Jessica; Leffin, Melissa; Francois, Laetitia Claire; Spinelli, Jennifer
IRB No: ARST1431
Protocol Abbrev: ARST1431
Principal Investigator: Don E. Eslin, MD
Phase: Drug: Phase III
Age Group: Pediatric
Secondary Protocol No: ARST1431
Treatment: Procedure:surgery radiotherapy VAC (Vincristine, Dactinomycin, Cyclophosphamide) alternating with VI (Vincristine/Irinotecan) (VAC/VI) to that of patients treated with surgery ,radiotherapy and VAC/VI plus temsirolimus (TORI)
Therapies Involved: Surgery; Radiation
ClinicalTrials.gov ID: NCT02567435
To compare the EFS and the OS of patients with IR RMS treated with surgery, radiotherapy, and Vac alternating with VI(VAC/VI) to that of patients treated with surgery, radiotherapy and VAC/VI plus temsirolimus (TORI)
To compare the outcome of patients based on their FOXO1 fusion gene partner by evaluating PAX3 vs PAX7 in all patients found to be FOXO1 fusion positive.
To compare the outcome of patients based on their FDG-PET response at Week 9 ( positive or negative ), as assessed by Deauville Criteria
Feasibility Phase: Patients must be < 21 years of age at the time of enrollment.
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 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 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 ARMS in the 2013 WHO Classification is the same as in the ICR and includes classic and solid variants.
• 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
Lansky score ≥ 50 for patients ≤ 16 years of age.
Karnofsky score ≥ 50 for patients >16 years of age.
220.127.116.11 Adequate Bone Marrow Function Defined As:
- Peripheral absolute neutrophil count (ANC) ≥ 750/μL
- Platelet count ≥ 75,000/μL
18.104.22.168 Adequate renal function defined as:
- Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m2 or A serum creatinine based on age/gender
Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
Patients who have previously received TORI, another mTOR inhibitor, or any other investigational agent
Patients who have received any chemotherapy (excluding steroids) and/or radiation therapy prior to this enrollment.
Patients with uncontrolled hyperglycemia
Patients with uncontrolled hyperlipidemia.
Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for at least 3 months after treatment is completed if sexually active with reproductive potential.
Female patients who are pregnant are not eligible since fetal toxicities or teratogenic effects have been noted for several of the study drugs.
Lactating females who plan to breastfeed their infants are not eligible.