ARST08P1, A Pilot Study to Evaluate Novel Agents (Temozolomide and Cixutumumab [IMC-A12, Anti-IGF-IR Monoclonal Antibody, IND #100947, NSC #742460]) in Combination with Intensive Multi-Agent Interval Compressed Therapy for Patients with High-Risk Rhabdomyosarcoma

Summary

This study consists of 2 pilots. Each of the 2 pilots will consist of 51 weeks of therapy. The dose of IMC-A12 to be administered to the first 20 patients enrolled on Pilot 1 is 3 mg/kg/dose (Cohort 1A). Following the enrollment of the first 20 patients on Pilot 1, accrual to this pilot study will be temporarily suspended to monitor for cardiac toxicity. Pilot 2 (Cohort 2) will start enrollment during the time Pilot 1 is suspended for assessment of cardiac toxicity. After enrollment of 20 patients on Pilot 2 and if no excessive cardiac toxicity is seen in the initial Pilot 1 cohort treated at 3 mg/kg/dose, Pilot 1 will reopen to 20 new patients with an increased dose of IMC-A12 at 6 mg/kg/dose (Cohort 1B). Accrual to Pilot 1 will again be temporarily closed pending assessment of cardiac toxicity at an IMC-A12 dose of 6 mg/kg/dose and enrollment to Pilot 2 will resume to an additional 20 patients. Once enrollment to Pilot 2 has been completed and if no excessive toxicity is seen in the Pilot 1 cohort treated at 6 mg/kg/dose (Cohort 1B), Pilot 1 will reopen to accrual at 9 mg/kg/dose (Cohort 1C). Once both pilots have reached accrual goals, the pilot which is feasible and felt to be most compelling for future study will be expanded up to a total of 75 patients.
Most patients should begin radiation therapy to the primary tumor and adjacent metastatic sites at Week 20. Patients requiring emergency radiation therapy (for intracranial extension or spinal cord impingement) should begin Week 1 chemotherapy concurrently with radiation therapy. Administration of IMC-A12 should be withheld during all radiation therapy. For the following study drugs, dosing is determined by age at the time the therapy is given: cyclophosphamide, dactinomycin, DOXOrubicin, etoposide, ifosfamide, and vinCRIStine. For temozolomide, dosing also changes when the patient’s BSA reaches 0.5 m2.

Participant Eligibility

Patients must be eligible for, and enrolled on D9902 (IRB File# 0999-398, A COG Soft Tissue Sarcoma Biology and Banking Protocol) prior to enrollment on ARST08P1.
< 50 years at the time of enrollment.
Patients with newly diagnosed, biopsy-proven metastatic rhabdomyosarcoma or ectomesenchymoma (Stage IV, Clinical Group IV) are eligible for this study. Patients with Stage IV, Clinical Group IV RMS with parameningeal and paraspinal primary tumors, including those with intracranial extension (ICE) are eligible for ARST08P1.
Patients must have a performance status corresponding to ECOG scores of 0, 1, or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years of age.
No prior chemotherapy or radiotherapy except for use of corticosteroids or emergent radiation therapy.
Patients requiring emergency radiation are eligible.
Adequate renal, liver, cardiac, and hematological function.
Sexually active patients of childbearing potential must agree to use effective contraception during therapy
(Pilots 1 and 2) and for at least 3 months after the last dose of IMC-A12 (Pilots 1).
All patients and/or their parents or legal guardians must sign a written informed consent.
All institutional, FDA, and NCI requirements for human studies must be met.