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
Intervention: Cixutumumab; Laboratory Biomarker Analysis; Temsirolimus
Intervention description: Given IV; Correlative studies; Given IV
Intervention MeSH terms: Sirolimus; Temsirolimus; MTOR Inhibitors; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 1 Year
Maximum age: 30 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with any of the following tumors who have experienced relapse following
             front-line therapy, or who are refractory to front-line therapy, are eligible:

               -  Osteosarcoma

               -  Ewing sarcoma/peripheral primitive neuroectodermal tumor (PNET)

               -  Rhabdomyosarcoma

               -  Non-rhabdomyosarcoma soft tissue sarcoma

          -  Patients must have had histologic verification of malignancy at original diagnosis or
             relapse

          -  All patients are required to submit archival tumor samples for immunohistochemical
             analysis (either paraffin-embedded tumor blocks or unstained slides)

               -  Tissue samples collected at original diagnosis or at relapse or at any subsequent
                  resections or biopsies should be available and ready for shipment to the
                  Biopathology Center (BPC) at time of study enrollment; the samples are required
                  even if tissue samples have previously been sent to the BPC for other purposes or
                  studies; blocks or slides should be shipped to the BPC within 7 days of study
                  enrollment

          -  Patients must have radiographically measurable disease

               -  Measurable disease is defined as the presence of at least one lesion on magnetic
                  resonance imaging (MRI) or computed tomography (CT) scan that can be accurately
                  measured with the longest diameter a minimum of 10 mm in at least one dimension
                  (CT scan slice thickness no greater than 5 mm)

               -  The following do not qualify as measurable disease:

                    -  Malignant fluid collections (e.g., ascites, pleural effusions)

                    -  Bone marrow infiltration

                    -  Lesions only detected by nuclear medicine studies (e.g., bone, gallium, or
                       positron emission tomography [PET] scans)

                    -  Elevated tumor markers in plasma or cerebrospinal fluid(CSF)

                    -  Previously radiated lesions that have not demonstrated clear progression
                       post radiation

                    -  Leptomeningeal lesions that do not meet the measurements noted above

          -  Patient?s current disease state must be one for which there is no known curative
             therapy or therapy proven to prolong survival with an acceptable quality of life

          -  Patients with known central nervous system metastases are excluded unless treated
             surgically or with radiotherapy and stable with no recurrent lesions for at least 3
             months

          -  Patients must have a Lansky or Karnofsky performance status score of ? 50%,
             corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1, or 2; use
             Karnofsky for patients > 16 years of age and Lansky for patients ? 16 years of age

               -  Patients who are unable to walk because of paralysis, but who are up in a
                  wheelchair, will be considered ambulatory for the purpose of assessing the
                  performance score

          -  For patients with solid tumors without bone marrow involvement:

               -  Peripheral absolute neutrophil count (ANC) ? 1,000/?L

               -  Platelet count ? 100,000/?L (transfusion independent, defined as not receiving
                  platelet transfusions within a 7-day period prior to enrollment)

               -  Hemoglobin ? 8.0 g/dL (may receive red blood cell [RBC] transfusions)

          -  For patients with solid tumors and known bone marrow metastatic disease:

               -  ANC ? 750/?L

               -  Platelet count ? 50,000/?L (may receive platelet transfusions)

               -  Hemoglobin ? 8.0 g/dL (may receive RBC transfusions)

                    -  For patients with known bone marrow metastatic disease, transfusions are
                       permitted to meet both platelet and hemoglobin criteria; patients must not
                       be known to be refractory to red blood cell or platelet transfusions

          -  Creatinine clearance or radioisotope GFR ? 70 mL/min OR a serum creatinine based on
             age/gender as follows:

               -  0.6 mg/dL (1 to < 2 years of age)

               -  0.8 mg/dL (2 to < 6 years of age)

               -  1.0 mg/dL (6 to < 10 years of age)

               -  1.2 mg/dL (10 to < 13 years of age)

               -  1.5 mg/dL (males) or 1.4 mg/dL (females) (13 to < 16 years of age)

               -  1.7 mg/dL (males) or 1.4 mg/dL (females) ( ? 16 years of age)

          -  Total bilirubin ? 1.5 times upper limit of normal (ULN)

          -  Serum glutamic pyruvate transaminase(SGPT) (alanine aminotransaminase [ALT]) ? 2.5
             times ULN (for the purpose of this study, the ULN for SGPT is 45 U/L)

          -  Serum albumin ? 2 g/dL

          -  Patients with seizure disorder may be enrolled if receiving non-enzyme-inducing
             anticonvulsants and well controlled

          -  Patients with known type I or type II diabetes mellitus are not eligible

          -  Serum glucose values must be within the normal limits for age; if the initial blood
             glucose is a random sample that is outside normal limits, then a follow-up fasting
             blood glucose should be obtained and must be within the normal limits for age

          -  Serum cholesterol levels must be < grade 2 (< 300 mg/dL), and serum triglyceride
             levels must be < grade 2 (< 2.5 times ULN)

          -  Patients who are pregnant or breast-feeding are not eligible for this study

          -  Negative pregnancy tests must be obtained in girls who are post-menarchal

          -  Males or females of reproductive potential may not participate unless they have agreed
             to use an effective contraceptive method for the duration of the study and for 3
             months after the last dose of cixutumumab

          -  Patients who have an uncontrolled infection are not eligible

          -  Patients who, in the opinion of the investigator, may not be able to comply with the
             safety monitoring requirements of the study are not eligible

          -  See Disease Characteristics

          -  There is no limit to the number of prior treatment regimens; however, patients must
             have fully recovered from the acute toxic effects of all prior chemotherapy,
             immunotherapy, or radiotherapy prior to study enrollment

          -  Patients must not have received myelosuppressive chemotherapy within 3 weeks of
             enrollment (6 weeks if prior nitrosourea)

          -  At least 7 days must have elapsed since the completion of therapy with a growth
             factor; at least 14 days must have elapsed after receiving pegfilgrastim

          -  At least 7 days must have elapsed since the completion of therapy with a biologic
             agent; for agents that have known adverse events occurring beyond 7 days after
             administration, this period prior to enrollment must be extended beyond the time
             during which adverse events are known to occur

          -  At least 3 half-lives must have elapsed since prior therapy that included a monoclonal
             antibody

          -  ? 2 weeks must have elapsed since local palliative radiotherapy (XRT) (small port); 3
             months must have elapsed if 50% radiation of pelvis; 6 weeks must have elapsed if
             therapeutic doses of metaiodobenzylguanidine(MIBG) or other substantial bone marrow
             irradiation was given

          -  No evidence of active graft-vs-host disease and 2 months must have elapsed since stem
             cell transplant or rescue

          -  Growth factors that support platelet or white cell number or function must not have
             been administered within the 7 days prior to enrollment (14 days if Neulasta?)

          -  Patients receiving corticosteroids who have not been on a stable or decreasing dose of
             corticosteroid for the 7 days prior to enrollment are not eligible

          -  Patients who are currently receiving another investigational drug are not eligible

          -  Patients who are currently receiving other anti-cancer agents, including chemotherapy,
             radiotherapy, immunotherapy, or biologic therapy, are not eligible

          -  Patients receiving insulin or growth hormone therapy are not eligible

          -  Patients who are receiving enzyme-inducing anticonvulsants are not eligible

          -  Use of warfarin is not allowed while on study; patients already on warfarin should use
             alternative anticoagulants while on this study; warfarin must not have been
             administered within 7 days of starting protocol therapy

          -  Patients who have received prior therapy targeting IGF-1R with either monoclonal
             antibodies or small molecule tyrosine kinase inhibitors are NOT eligible

          -  Prior treatment with mTOR inhibitors (e.g., rapamycin, temsirolimus, everolimus,
             deforolimus) is NOT allowed

          -  Patients who have had major surgery within 3 weeks prior to enrollment are not
             eligible; procedures such as placement of a central vascular catheter or limited tumor
             biopsy are not considered major surgery