Clinical Trials

Temozolomide, Cixutumumab, and Combination Chemotherapy in Treating Patients With Metastatic Rhabdomyosarcoma

Location:

Rochester,  MN

Trial status:

Open for Enrollment

Why is this study being done?

PRIMARY OBJECTIVES:

I. To determine the feasibility of administering cixutumumab in combination with an intensive multi-agent interval compressed chemotherapy regimen for the treatment of high-risk metastatic rhabdomyosarcoma (RMS).

II. To determine the feasibility of adding temozolomide to vincristine and irinotecan in these patients.

III. To assess immediate and short-term side effects of concurrent temozolomide, vincristine, and irinotecan with radiotherapy in these patients.

SECONDARY OBJECTIVES:

I. To gain a preliminary estimate of the response rate to cixutumumab or temozolomide, vincristine, and irinotecan in these patients.

II. To obtain preliminary efficacy data for cixutumumab or temozolomide in combination with an intensive multi-agent interval compressed chemotherapy regimen in these patients.

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 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 IV 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 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 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 radiotherapy* 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 radiotherapy* as in group 1. Patients also receive oral temozolomide 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 radiotherapy* 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 radiotherapy starting in week 1; cixutumumab should be withheld during radiotherapy.

After completion of study therapy, patients are followed up periodically for up to 10 years.

Who is eligible to participate?

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

Last updated: 04/01/2013

NCT ID:

NCT01055314