Temozolomide, Cixutumumab, and Combination Chemotherapy in Treating Patients With Metastatic Rhabdomyosarcoma
Condition: Adult Rhabdomyosarcoma; Childhood Alveolar Rhabdomyosarcoma; Childhood Embryonal Rhabdomyosarcoma; Metastatic Childhood Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Untreated Childhood Rhabdomyosarcoma
MeSH terms: Sarcoma; Rhabdomyosarcoma; Rhabdomyosarcoma, Alveolar; Rhabdomyosarcoma, Embryonal
Intervention: Cixutumumab; Cyclophosphamide; Dactinomycin; Doxorubicin Hydrochloride; Etoposide; Ifosfamide; Irinotecan Hydrochloride; Laboratory Biomarker Analysis; Temozolomide; Vincristine Sulfate Liposome
Intervention description: Given IV; Given IV; Given IV; Given IV; Given IV; Given IV; Given IV; Correlative studies; Given PO; Given IV
Intervention MeSH terms: Dactinomycin; Cyclophosphamide; Temozolomide; Ifosfamide; Isophosphamide mustard; Doxorubicin; Liposomal doxorubicin; Irinotecan; Etoposide; Vincristine; Etoposide phosphate; Podophyllotoxin; Camptothecin; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 175.0
Sex: All
Maximum age: 49 Years
Healthy volunteers: No

Summary:

      This randomized pilot clinical trial is studying the side effects and how well giving
      temozolomide and cixutumumab together with combination chemotherapy works in treating
      patients with metastatic rhabdomyosarcoma. Drugs used in chemotherapy, such as temozolomide,
      work in different ways to stop the growth of tumor cells, either by killing the cells or by
      stopping them from dividing. Monoclonal antibodies, such as cixutumumab, can block tumor
      growth in different ways. Some block the ability of tumor cells to grow and spread. Others
      find tumor cells and help kill them or carry tumor-killing substances to them. Giving
      temozolomide and cixutumumab together with combination chemotherapy may kill more tumor
      cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must be eligible for, and enrolled on D9902 prior to enrollment on ARST08P1

          -  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; ICE is
             defined 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; ICE is also presumed
             to exist if the cerebrospinal fluid (CSF) cytopathology is positive for tumor at
             diagnosis

          -  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

          -  No prior chemotherapy or radiotherapy except for use of corticosteroids or emergent
             radiation therapy; patients requiring emergency radiation are eligible

          -  Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
             mL/min/1.73m^2 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 x 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

          -  Absolute neutrophil count (ANC) >= 750/uL; abnormal blood counts are permissible if
             there is bone marrow biopsy or aspirate proven bone marrow involvement by
             rhabdomyosarcoma

          -  Platelet count >= 75,000/uL; abnormal blood counts are permissible if there is bone
             marrow biopsy or aspirate proven bone marrow involvement by rhabdomyosarcoma

          -  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)

        Exclusion Criteria:

          -  Female patients who are pregnant are not eligible

          -  Female patients who are breastfeeding are not eligible; female patients who are
             lactating must agree to stop breastfeeding to participate in this study

          -  Patients receiving growth hormone therapy are not eligible

          -  Patients with known type I or type II diabetes mellitus are not eligible for
             enrollment on Pilot 1

          -  Patients with evidence of uncontrolled infection are not eligible

          -  All patients and/or their parents or legal guardians must sign a written informed
             consent

          -  All institutional, Food and Drug Administration (FDA), and National Cancer Institute
             (NCI) requirements for human studies must be met