Cixutumumab and Temsirolimus in Treating Younger Patients With Recurrent or Refractory Sarcoma
Condition: Childhood Alveolar Soft Part Sarcoma; Childhood Angiosarcoma; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Gliosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Peripheral Nerve Sheath Tumor; Childhood Synovial Sarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Osteosarcoma; Rhabdomyosarcoma
MeSH terms: Sarcoma; Osteosarcoma; Rhabdomyosarcoma; Sarcoma, Ewing; Gliosarcoma; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Leiomyosarcoma; Liposarcoma; Rhabdomyosarcoma, Embryonal; Neuroectodermal Tumors, Primitive, Peripheral; Sarcoma, Synovial; Hemangiosarcoma; Nerve Sheath Neoplasms; Neurofibrosarcoma; Fibrosarcoma; Sarcoma, Alveolar Soft Part; Recurrence
Study type: Interventional
Phase: Phase 2

Summary: 
      This phase II trial studies how well cixutumumab and temsirolimus work in treating patients
      with recurrent or refractory sarcoma. 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.
      Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for
      cell growth. Giving cixutumumab and temsirolimus together may kill more tumor cells.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To determine the objective response rate to the combination of cixutumumab and
      temsirolimus in patients with relapsed or refractory osteosarcoma, Ewing sarcoma,
      rhabdomyosarcoma, or non-rhabdomyosarcoma soft tissue sarcoma.

      II. To further describe the toxicities (including dose-limiting toxicities) of cixutumumab
      and temsirolimus administered on this schedule.

      SECONDARY OBJECTIVES:

      I. To assess the progression-free survival for patients treated in each disease stratum with
      this drug combination.

      II. To assess the incidence of insulin-like growth factor 1 receptor (IGF-1R), insulin
      receptor, ERK, RON, and mammalian target of rapamycin (mTOR) pathway activation in archival
      tumor material, and correlate with response.

      III. To evaluate minimal residual disease and IGF-1R tumor cell expression in the blood and
      bone marrow of Ewing sarcoma patients using flow cytometry.

      OUTLINE: This is a multicenter study. Patients are stratified according to diagnosis
      (osteosarcoma vs Ewing sarcoma/PNET vs rhabdomyosarcoma vs non-rhabdomyosarcoma soft tissue
      sarcoma).

      Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8,
      15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease
      progression or unacceptable toxicity.

      Archived tumor tissue samples from most recent biopsy are collected and analyzed for IGF-1R,
      insulin receptor, AKT, ERK, mTOR, and S6 kinase pathway activation by immunohistochemistry
      (IHC) and banked for future correlative studies. Blood and bone marrow samples, from patients
      with Ewing sarcoma, may be collected at baseline and periodically during treatment for
      minimal residual disease analysis by flow cytometry.

      After completion of study treatment, patients are followed up periodically for 5 years.
    

Intervention name(s): Cixutumumab; Laboratory Biomarker Analysis; Temsirolimus
Intervention type(s): Biological; Other; Drug
Intervention description(s): Given IV; Correlative studies; Given IV
Other intervention name(s): Anti-IGF-1R Recombinant Monoclonal Antibody IMC-A12; IMC-A12; CCI-779; CCI-779 Rapamycin Analog; Cell Cycle Inhibitor 779; Rapamycin Analog; Rapamycin Analog CCI-779; Torisel
Intervention MeSH terms: Sirolimus; Temsirolimus; MTOR Inhibitors; Antibodies, Monoclonal
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment