{
    "info": {
        "nct_id": "NCT00880282",
        "official_title": "A Phase I Study of IMC-A12 (Anti-Insulin-Like Growth Factor-I Receptor Monoclonal Antibody) in Combination With CCI-779 (Temsirolimus) in Pediatric Patients With Recurrent or Refractory Solid Tumors",
        "inclusion_criteria": "* Patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of serum or cerebrospinal fluid (CSF) alpha-fetoprotein or beta-human chorionic gonadotropin (HCG); slides or tissue blocks from either initial diagnosis or relapse must be available for central review\n* Patients must have either measurable or evaluable disease\n* 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\n* Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; note: neurologic deficits in patients with central nervous system (CNS) tumors must have been clinically stable for a minimum of 1 week prior to study enrollment; 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\n* Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study\n\n  * Myelosuppressive chemotherapy: must not have received within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)\n  * Hematopoietic growth factors: at least 7 days since the completion of therapy with a growth factor that supports platelet or white cell number or function\n  * Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with a biologic agent; at least 6 weeks must have elapsed since prior therapy that includes a monoclonal antibody; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair\n  * Radiation therapy (XRT): >= 2 wks for local palliative XRT (small port); >= 3 months must have elapsed if prior total-body irradiation (TBI), craniospinal XRT or if >= 50% radiation of pelvis; >= 6 wks must have elapsed if other substantial bone marrow (BM) radiation\n  * Stem cell transplant or rescue: no evidence of active graft vs. host disease and >= 2 months must have elapsed since transplant\n* Peripheral absolute neutrophil count (ANC) >= 1000/mm^3\n* Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)\n* Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)\n* Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR a serum creatinine based on age/gender as follows:\n\n  * 0.6 mg/dL (for patients 1 year of age)\n  * 0.8 mg/dL (for patients 2 to 5 years of age)\n  * 1 mg/dL (for patients 6 to 9 years of age)\n  * 1.2 mg/dL (for patients 10 to 12 years of age)\n  * 1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)\n  * 1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients >= 16 years of age)\n* Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age\n* Serum albumin >= 2 g/dL\n* Patients with seizure disorder may be enrolled if receiving non-enzyme inducing anticonvulsants and well controlled\n* Prothrombin time (PT) and international normalized ratio (INR) < 1.2 x ULN\n* Random or fasting blood glucose within the upper normal limits for age; if the initial blood glucose is a random sample that is outside of the normal limits, then a follow-up fasting blood glucose can be obtained and must be within the upper normal limits for age\n* Serum cholesterol and serum triglyceride levels must be < grade 2\n* All patients and/or their parents or legal guardians must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines\nHealthy volunteers allowed\nMust have minimum age of 1 Year\nMust have maximum age of 21 Years",
        "exclusion_criteria": "* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L\n* Pregnant or breast-feeding women will not be entered on this study; 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 IMC-A12.\n* 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\n* Patients who are currently receiving another investigational drug are not eligible\n* Patients who are currently receiving other anticancer agents are not eligible\n* Patients receiving insulin or growth hormone therapy are not eligible\n* Patients must not be receiving enzyme-inducing anticonvulsants\n* Patients must not be receiving any of the following potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers or inhibitors: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort\n* Patients receiving warfarin for the purpose of systemic anticoagulation are not eligible; use of low-dose warfarin for maintaining patency of central venous catheters is allowed\n* Patients who have an uncontrolled infection are not eligible\n* Patients with known type I or type II diabetes mellitus are not eligible\n* Patients with known bone marrow involvement are not eligible\n* 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\n* Patients who have received prior monoclonal antibody therapy targeting IGF-1R or temsirolimus are not eligible\n* Patients with history of allergic reactions attributed to compounds of similar chemical; or biologic composition to IMC-A12 or temsirolimus are not eligible\n* Patients must not have had major surgery for 6 weeks prior to enrollment on the study; patients with history of recent minor surgical procedures (vascular catheter placement, bone marrow evaluation, laparoscopic surgery) will be eligible",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of serum or cerebrospinal fluid (CSF) alpha-fetoprotein or beta-human chorionic gonadotropin (HCG); slides or tissue blocks from either initial diagnosis or relapse must be available for central review",
            "criterions": [
                {
                    "exact_snippets": "histologic verification of malignancy",
                    "criterion": "malignancy verification",
                    "requirements": [
                        {
                            "requirement_type": "verification",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "intrinsic brain stem tumors",
                    "criterion": "intrinsic brain stem tumors",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "optic pathway gliomas",
                    "criterion": "optic pathway gliomas",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "pineal tumors and elevations of serum or cerebrospinal fluid (CSF) alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)",
                    "criterion": "pineal tumors with elevated markers",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "slides or tissue blocks from either initial diagnosis or relapse must be available for central review",
                    "criterion": "slides or tissue blocks availability",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have either measurable or evaluable disease",
            "criterions": [
                {
                    "exact_snippets": "measurable or evaluable disease",
                    "criterion": "disease",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "measurable",
                                "evaluable"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 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",
            "criterions": [
                {
                    "exact_snippets": "Patient's current disease state must be one for which there is no known curative therapy",
                    "criterion": "current disease state",
                    "requirements": [
                        {
                            "requirement_type": "curative therapy",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Patient's current disease state must be one for which there is no ... therapy proven to prolong survival with an acceptable quality of life",
                    "criterion": "current disease state",
                    "requirements": [
                        {
                            "requirement_type": "therapy proven to prolong survival with an acceptable quality of life",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; note: neurologic deficits in patients with central nervous system (CNS) tumors must have been clinically stable for a minimum of 1 week prior to study enrollment; 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",
            "criterions": [
                {
                    "exact_snippets": "Karnofsky >= 50% for patients > 16 years of age",
                    "criterion": "Karnofsky performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "%"
                            }
                        },
                        {
                            "requirement_type": "age",
                            "expected_value": {
                                "operator": ">",
                                "value": 16,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Lansky >= 50 for patients =< 16 years of age",
                    "criterion": "Lansky performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "N/A"
                            }
                        },
                        {
                            "requirement_type": "age",
                            "expected_value": {
                                "operator": "<=",
                                "value": 16,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "neurologic deficits in patients with central nervous system (CNS) tumors must have been clinically stable for a minimum of 1 week prior to study enrollment",
                    "criterion": "neurologic deficits stability",
                    "requirements": [
                        {
                            "requirement_type": "stability duration",
                            "expected_value": "minimum of 1 week"
                        }
                    ]
                },
                {
                    "exact_snippets": "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",
                    "criterion": "ambulatory status",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "unable to walk because of paralysis"
                        },
                        {
                            "requirement_type": "mobility aid",
                            "expected_value": "up in a wheelchair"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study",
            "criterions": [
                {
                    "exact_snippets": "fully recovered from the acute toxic effects of all prior chemotherapy",
                    "criterion": "recovery from acute toxic effects of prior chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "recovery",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "fully recovered from the acute toxic effects of all prior ... immunotherapy",
                    "criterion": "recovery from acute toxic effects of prior immunotherapy",
                    "requirements": [
                        {
                            "requirement_type": "recovery",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "fully recovered from the acute toxic effects of all prior ... radiotherapy",
                    "criterion": "recovery from acute toxic effects of prior radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "recovery",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Myelosuppressive chemotherapy: must not have received within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)",
            "criterions": [
                {
                    "exact_snippets": "Myelosuppressive chemotherapy: must not have received within 3 weeks of enrollment",
                    "criterion": "myelosuppressive chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 3,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "(6 weeks if prior nitrosourea)",
                    "criterion": "prior nitrosourea",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 6,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hematopoietic growth factors: at least 7 days since the completion of therapy with a growth factor that supports platelet or white cell number or function",
            "criterions": [
                {
                    "exact_snippets": "Hematopoietic growth factors: at least 7 days since the completion of therapy with a growth factor that supports platelet or white cell number or function",
                    "criterion": "hematopoietic growth factor therapy",
                    "requirements": [
                        {
                            "requirement_type": "completion time",
                            "expected_value": {
                                "operator": ">=",
                                "value": 7,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with a biologic agent; at least 6 weeks must have elapsed since prior therapy that includes a monoclonal antibody; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair",
            "criterions": [
                {
                    "exact_snippets": "at least 7 days since the completion of therapy with a biologic agent",
                    "criterion": "completion of therapy with a biologic agent",
                    "requirements": [
                        {
                            "requirement_type": "time since completion",
                            "expected_value": {
                                "operator": ">=",
                                "value": 7,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "at least 6 weeks must have elapsed since prior therapy that includes a monoclonal antibody",
                    "criterion": "prior therapy that includes a monoclonal antibody",
                    "requirements": [
                        {
                            "requirement_type": "time since completion",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur",
                    "criterion": "agents with known adverse events occurring beyond 7 days after administration",
                    "requirements": [
                        {
                            "requirement_type": "time since completion",
                            "expected_value": "extended beyond the time during which adverse events are known to occur"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Radiation therapy (XRT): >= 2 wks for local palliative XRT (small port); >= 3 months must have elapsed if prior total-body irradiation (TBI), craniospinal XRT or if >= 50% radiation of pelvis; >= 6 wks must have elapsed if other substantial bone marrow (BM) radiation",
            "criterions": [
                {
                    "exact_snippets": "Radiation therapy (XRT): >= 2 wks for local palliative XRT (small port)",
                    "criterion": "local palliative XRT (small port)",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": ">= 3 months must have elapsed if prior total-body irradiation (TBI)",
                    "criterion": "prior total-body irradiation (TBI)",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": ">= 3 months must have elapsed if ... craniospinal XRT",
                    "criterion": "craniospinal XRT",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": ">= 3 months must have elapsed if ... >= 50% radiation of pelvis",
                    "criterion": "radiation of pelvis",
                    "requirements": [
                        {
                            "requirement_type": "extent of radiation",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "%"
                            }
                        },
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": ">= 6 wks must have elapsed if other substantial bone marrow (BM) radiation",
                    "criterion": "substantial bone marrow (BM) radiation",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Stem cell transplant or rescue: no evidence of active graft vs. host disease and >= 2 months must have elapsed since transplant",
            "criterions": [
                {
                    "exact_snippets": "Stem cell transplant or rescue: no evidence of active graft vs. host disease",
                    "criterion": "graft vs. host disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": ">= 2 months must have elapsed since transplant",
                    "criterion": "time since transplant",
                    "requirements": [
                        {
                            "requirement_type": "time elapsed",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Peripheral absolute neutrophil count (ANC) >= 1000/mm^3",
            "criterions": [
                {
                    "exact_snippets": "Peripheral absolute neutrophil count (ANC) >= 1000/mm^3",
                    "criterion": "peripheral absolute neutrophil count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1000,
                                "unit": "mm^3"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)",
            "criterions": [
                {
                    "exact_snippets": "Platelet count >= 100,000/mm^3",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100000,
                                "unit": "mm^3"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment",
                    "criterion": "platelet transfusion independence",
                    "requirements": [
                        {
                            "requirement_type": "absence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin >= 8.0 g/dL",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 8.0,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR a serum creatinine based on age/gender as follows:",
            "criterions": [
                {
                    "exact_snippets": "Creatinine clearance ... >= 70 mL/min/1.73 m^2",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 70,
                                "unit": "mL/min/1.73 m^2"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2",
                    "criterion": "radioisotope glomerular filtration rate (GFR)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 70,
                                "unit": "mL/min/1.73 m^2"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "serum creatinine based on age/gender",
                    "criterion": "serum creatinine",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": "based on age/gender"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 0.6 mg/dL (for patients 1 year of age)",
            "criterions": [
                {
                    "exact_snippets": "0.6 mg/dL (for patients 1 year of age)",
                    "criterion": "serum creatinine level",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "=",
                                "value": 0.6,
                                "unit": "mg/dL"
                            }
                        },
                        {
                            "requirement_type": "age",
                            "expected_value": {
                                "operator": "=",
                                "value": 1,
                                "unit": "year"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 0.8 mg/dL (for patients 2 to 5 years of age)",
            "criterions": [
                {
                    "exact_snippets": "0.8 mg/dL (for patients 2 to 5 years of age)",
                    "criterion": "serum creatinine level",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "=",
                                "value": 0.8,
                                "unit": "mg/dL"
                            }
                        },
                        {
                            "requirement_type": "age",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 2,
                                        "unit": "years"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 1 mg/dL (for patients 6 to 9 years of age)",
            "criterions": [
                {
                    "exact_snippets": "1 mg/dL (for patients 6 to 9 years of age)",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 6,
                                        "unit": "years"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 9,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "1 mg/dL",
                    "criterion": "measurement",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "=",
                                "value": 1,
                                "unit": "mg/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 1.2 mg/dL (for patients 10 to 12 years of age)",
            "criterions": [
                {
                    "exact_snippets": "1.2 mg/dL (for patients 10 to 12 years of age)",
                    "criterion": "serum creatinine",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "=",
                                "value": 1.2,
                                "unit": "mg/dL"
                            }
                        },
                        {
                            "requirement_type": "age",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 10,
                                        "unit": "years"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 12,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)",
            "criterions": [
                {
                    "exact_snippets": "1.5 mg/dL (males)",
                    "criterion": "serum creatinine level",
                    "requirements": [
                        {
                            "requirement_type": "maximum value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "mg/dL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "1.4 mg/dL (females)",
                    "criterion": "serum creatinine level",
                    "requirements": [
                        {
                            "requirement_type": "maximum value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.4,
                                "unit": "mg/dL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "patients 13 to 15 years of age",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 13,
                                        "unit": "years"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 15,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients >= 16 years of age)",
            "criterions": [
                {
                    "exact_snippets": "1.7 mg/dL (males)",
                    "criterion": "serum creatinine level (males)",
                    "requirements": [
                        {
                            "requirement_type": "maximum value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.7,
                                "unit": "mg/dL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "1.4 mg/dL (females)",
                    "criterion": "serum creatinine level (females)",
                    "requirements": [
                        {
                            "requirement_type": "maximum value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.4,
                                "unit": "mg/dL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "patients >= 16 years of age",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 16,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age",
            "criterions": [
                {
                    "exact_snippets": "Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age",
                    "criterion": "bilirubin level",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 1.5,
                                        "unit": "x ULN for age"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Serum albumin >= 2 g/dL",
            "criterions": [
                {
                    "exact_snippets": "Serum albumin >= 2 g/dL",
                    "criterion": "serum albumin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with seizure disorder may be enrolled if receiving non-enzyme inducing anticonvulsants and well controlled",
            "criterions": [
                {
                    "exact_snippets": "Patients with seizure disorder",
                    "criterion": "seizure disorder",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "receiving non-enzyme inducing anticonvulsants",
                    "criterion": "anticonvulsant medication",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": "non-enzyme inducing"
                        }
                    ]
                },
                {
                    "exact_snippets": "well controlled",
                    "criterion": "seizure control",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "well controlled"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prothrombin time (PT) and international normalized ratio (INR) < 1.2 x ULN",
            "criterions": [
                {
                    "exact_snippets": "Prothrombin time (PT) ... < 1.2 x ULN",
                    "criterion": "Prothrombin time (PT)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.2,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "international normalized ratio (INR) < 1.2 x ULN",
                    "criterion": "international normalized ratio (INR)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.2,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Random or fasting blood glucose within the upper normal limits for age; if the initial blood glucose is a random sample that is outside of the normal limits, then a follow-up fasting blood glucose can be obtained and must be within the upper normal limits for age",
            "criterions": [
                {
                    "exact_snippets": "Random or fasting blood glucose within the upper normal limits for age",
                    "criterion": "blood glucose",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "random",
                                "fasting"
                            ]
                        },
                        {
                            "requirement_type": "range",
                            "expected_value": "within the upper normal limits for age"
                        }
                    ]
                },
                {
                    "exact_snippets": "if the initial blood glucose is a random sample that is outside of the normal limits, then a follow-up fasting blood glucose can be obtained and must be within the upper normal limits for age",
                    "criterion": "follow-up fasting blood glucose",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": "within the upper normal limits for age"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* All patients and/or their parents or legal guardians must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines",
            "criterions": [
                {
                    "exact_snippets": "All patients and/or their parents or legal guardians must sign a written informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "assent, when appropriate, will be obtained according to institutional guidelines",
                    "criterion": "assent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 1 Year",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 1 Year",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "Year"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have maximum age of 21 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 21 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 21,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L",
            "criterions": [
                {
                    "exact_snippets": "Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L",
                    "criterion": "SGPT (ALT) level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 110,
                                "unit": "U/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "ULN for SGPT is 45 U/L",
                    "criterion": "ULN for SGPT",
                    "requirements": [
                        {
                            "requirement_type": "upper limit of normal",
                            "expected_value": {
                                "operator": "=",
                                "value": 45,
                                "unit": "U/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant or breast-feeding women will not be entered on this study; 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 IMC-A12.",
            "criterions": [
                {
                    "exact_snippets": "Pregnant or breast-feeding women will not be entered on this study",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Pregnant or breast-feeding women will not be entered on this study",
                    "criterion": "breast-feeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "pregnancy tests must be obtained in girls who are post-menarchal",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method",
                    "criterion": "use of contraceptive method",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "for the duration of the study and for 3 months after the last dose of IMC-A12",
                    "criterion": "duration of contraceptive use",
                    "requirements": [
                        {
                            "requirement_type": "time period",
                            "expected_value": "for the duration of the study and for 3 months after the last dose of IMC-A12"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 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",
            "criterions": [
                {
                    "exact_snippets": "Patients receiving corticosteroids",
                    "criterion": "corticosteroid use",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment",
                    "criterion": "corticosteroid dose stability",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": "stable or decreasing"
                        },
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 7,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who are currently receiving another investigational drug are not eligible",
            "criterions": [
                {
                    "exact_snippets": "Patients who are currently receiving another investigational drug",
                    "criterion": "receiving another investigational drug",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who are currently receiving other anticancer agents are not eligible",
            "criterions": [
                {
                    "exact_snippets": "Patients who are currently receiving other anticancer agents",
                    "criterion": "current anticancer agent use",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients receiving insulin or growth hormone therapy are not eligible",
            "criterions": [
                {
                    "exact_snippets": "Patients receiving insulin ... are not eligible",
                    "criterion": "insulin therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients receiving ... growth hormone therapy are not eligible",
                    "criterion": "growth hormone therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must not be receiving enzyme-inducing anticonvulsants",
            "criterions": [
                {
                    "exact_snippets": "Patients must not be receiving enzyme-inducing anticonvulsants",
                    "criterion": "enzyme-inducing anticonvulsants",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must not be receiving any of the following potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers or inhibitors: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort",
            "criterions": [
                {
                    "exact_snippets": "Patients must not be receiving any of the following potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers or inhibitors: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort",
                    "criterion": "CYP3A4 inducers or inhibitors",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "specific substances",
                            "expected_value": [
                                "erythromycin",
                                "clarithromycin",
                                "ketoconazole",
                                "azithromycin",
                                "itraconazole",
                                "grapefruit juice",
                                "St. John's wort"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients receiving warfarin for the purpose of systemic anticoagulation are not eligible; use of low-dose warfarin for maintaining patency of central venous catheters is allowed",
            "criterions": [
                {
                    "exact_snippets": "Patients receiving warfarin for the purpose of systemic anticoagulation are not eligible",
                    "criterion": "warfarin use for systemic anticoagulation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "use of low-dose warfarin for maintaining patency of central venous catheters is allowed",
                    "criterion": "low-dose warfarin use for maintaining patency of central venous catheters",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have an uncontrolled infection are not eligible",
            "criterions": [
                {
                    "exact_snippets": "uncontrolled infection",
                    "criterion": "infection",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with known type I or type II diabetes mellitus are not eligible",
            "criterions": [
                {
                    "exact_snippets": "known type I or type II diabetes mellitus",
                    "criterion": "diabetes mellitus",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "type I",
                                "type II"
                            ]
                        },
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with known bone marrow involvement are not eligible",
            "criterions": [
                {
                    "exact_snippets": "known bone marrow involvement",
                    "criterion": "bone marrow involvement",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 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",
            "criterions": [
                {
                    "exact_snippets": "may not be able to comply with the safety monitoring requirements",
                    "criterion": "ability to comply with safety monitoring requirements",
                    "requirements": [
                        {
                            "requirement_type": "compliance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have received prior monoclonal antibody therapy targeting IGF-1R or temsirolimus are not eligible",
            "criterions": [
                {
                    "exact_snippets": "Patients who have received prior monoclonal antibody therapy targeting IGF-1R",
                    "criterion": "prior monoclonal antibody therapy targeting IGF-1R",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients who have received ... temsirolimus",
                    "criterion": "prior temsirolimus therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with history of allergic reactions attributed to compounds of similar chemical; or biologic composition to IMC-A12 or temsirolimus are not eligible",
            "criterions": [
                {
                    "exact_snippets": "history of allergic reactions attributed to compounds of similar chemical; or biologic composition to IMC-A12 or temsirolimus",
                    "criterion": "allergic reactions to compounds",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "composition",
                            "expected_value": [
                                "similar chemical",
                                "biologic"
                            ]
                        },
                        {
                            "requirement_type": "specific compounds",
                            "expected_value": [
                                "IMC-A12",
                                "temsirolimus"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must not have had major surgery for 6 weeks prior to enrollment on the study; patients with history of recent minor surgical procedures (vascular catheter placement, bone marrow evaluation, laparoscopic surgery) will be eligible",
            "criterions": [
                {
                    "exact_snippets": "Patients must not have had major surgery for 6 weeks prior to enrollment",
                    "criterion": "major surgery",
                    "requirements": [
                        {
                            "requirement_type": "time since last occurrence",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "patients with history of recent minor surgical procedures (vascular catheter placement, bone marrow evaluation, laparoscopic surgery) will be eligible",
                    "criterion": "minor surgical procedures",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "* Serum cholesterol and serum triglyceride levels must be < grade 2",
            "criterions": [
                {
                    "exact_snippets": "Serum cholesterol ... < grade 2",
                    "criterion": "serum cholesterol level",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<",
                                "value": 2,
                                "unit": "grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Serum triglyceride levels ... < grade 2",
                    "criterion": "serum triglyceride level",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<",
                                "value": 2,
                                "unit": "grade"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}