I. To determine the feasibility of administering IMC-A12 (cixutumumab) in combination with a
multi-agent intensive chemotherapy regimen for the treatment of high-risk rhabdomyosarcoma
II. To determine the feasibility of adding temozolomide to vincristine (vincristine
sulfate)/irinotecan (irinotecan hydrochloride) cycles in patients with high-risk RMS.
III. To assess immediate and short-term side effects of delivery of concurrent
temozolomide-vincristine-irinotecan with irradiation in patients with high-risk RMS.
I. To gain a preliminary estimate of the response rate to IMC-A12 or temozolomide plus
vincristine/irinotecan in previously untreated high-risk RMS.
II. To obtain preliminary efficacy data for IMC-A12 or temozolomide in combination with a
multi-agent interval compressed chemotherapy regimen in previously untreated high-risk RMS.
III. To determine the effectiveness of detecting metastatic disease with fludeoxyglucose F 18
positron emission tomography (FDG PET) and to compare assessment of response using standard
imaging techniques with response assessed by FDG PET.
IV. To assess changes in serum levels of insulin-like growth factor (IGF)-I, IGF-II, IGF-BP3
as biomarkers of IGF-IR inhibition.
OUTLINE: This is a dose-escalation study of cixutumumab. Patients are assigned to 1 of 2
treatment groups according to the timing of their enrollment onto the study.
GROUP 1: Patients receive vincristine sulfate intravenously (IV) over 1 minute on day 1 of
weeks 1-5, 7, 8, 11, 12, 15, 16, 20-24, 28, 29, 32, 33, 35, 38, 41-44, 47, 48, 50, and 51;
irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 1, 4, 20, 23, 47, and 50;
ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 of weeks 9, 13, 17, 26,
and 30; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 7, 11, 15,
28, and 32; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 7, 11, 15, 28, 32, 35,
38, 41, and 44; dactinomycin IV over 1-5 minutes on day 1 of weeks 35, 38, 41, and 44; and
cixutumumab IV over 1 hour on day 1 of weeks 1-51. Patients also undergo radiation therapy*
on days 1-5 of weeks 20-24.
GROUP 2: Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide,
etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin and undergo
radiation therapy* as in group 1. Patients also receive temozolomide orally (PO) on days 1-5
of weeks 1, 4, 20, 23, 47, and 50.
GROUP 3: Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide,
etoposide, doxorubicin hydrochloride, cyclophosphamide, dactinomycin, and cixutumumab and
undergo radiation therapy* as in group 1. Patients also receive temozolomide as in group 2.
(Discontinued as of January 2013)
NOTE: *Patients with parameningeal tumors and evidence of intracranial extension or those
requiring emergency radiotherapy may receive radiation therapy starting in week 1;
cixutumumab should be withheld during radiation therapy.
After completion of study therapy, patients are followed up at 3 weeks and then periodically
for up to 5 years.