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

Inclusion Criteria:

- Newly diagnosed, biopsy-confirmed metastatic rhabdomyosarcoma (RMS) or
ectomesenchymoma

- Stage IV, Clinical Group IV

- RMS with parameningeal and paraspinal primary tumors, including those with
intracranial extension by contrast magnetic resonance imaging (MRI) showing that the
primary tumor touches, displaces, invades, distorts, or otherwise causes signal
abnormality of the dura in brain or spinal cord in contiguity to the primary site,
are allowed; ICE is also presumed to exist if the cerebrospinal fluid (CSF)
cytopathology is positive for tumor at diagnosis

- Has undergone initial surgery (including biopsy) that provided the definitive
diagnosis within the past 42 days

- Enrollment on COG-D9902 required

- Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age

- Absolute neutrophil count (ANC) >= 750/μL

- Abnormal blood counts are permissible if there is bone marrow biopsy or aspirate
proven bone marrow involvement by RMS

- Platelet count >= 75,000/μL

- Abnormal blood counts are permissible if there is bone marrow biopsy or aspirate
proven bone marrow involvement by RMS

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min OR
maximum serum creatinine based on age/gender as follows:

- 0.4 mg/dL (for patients 1 to 5 months of age)

- 0.5 mg/dL (for patients 6 to 11 months of age)

- 0.6 mg/dL (for patients 1 year of age)

- 0.8 mg/dL (for patients 2 to 5 years of age)

- 1.0 mg/dL (for patients 6 to 9 years of age)

- 1.2 mg/dL (for patients 10 to 12 years of age)

- 1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)

- 1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients >= 16 years of age)

- Patients with urinary tract obstruction by tumor must meet the renal function
criteria listed above AND must have unimpeded urinary flow established via
decompression of the obstructed portion of the urinary tract

- Total bilirubin =< 1.5 times upper limit of normal (ULN) for age (unless there is
evidence of biliary obstruction by the tumor)

- Shortening fraction >=≥ 27% by echocardiogram (ECHO) OR ejection fraction >= 50% by
radionuclide angiogram

- Not pregnant or nursing

- Negative pregnancy test

- Sexually active patients of childbearing potential must agree to use effective
contraception during therapy (groups1 and 2) and for at least 3 months after the last
dose of cixutumumab (group 1)

- No uncontrolled infection

- No known type I or type II diabetes mellitus (for patients enrolled in group 1)

- No prior chemotherapy or radiotherapy except corticosteroids or emergent radiotherapy

- Patients requiring emergency radiation are eligible

- No concurrent growth hormone therapy

- All patients and/or their parents or legal guardians must sign a written informed
consent