{
    "info": {
        "nct_id": "NCT00699491",
        "official_title": "Phase I/II Trial of IMC-A12 in Combination With Temsirolimus in Patients With Metastatic Breast Cancer",
        "inclusion_criteria": "* Histologically confirmed diagnosis of breast cancer with diagnosis of metastatic or locally recurrent disease (locally recurrent disease should be stage IV e.g. chest wall involvement)\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 (Karnofsky >= 80%)\n* Life expectancy of > 12 weeks\n* Capable of understanding investigational nature, potential risks and benefits of the study and able to provide written informed consent\n* Negative serum pregnancy test =< 7 days of registration for women of childbearing potential:\n\n  * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study therapy and for 3 months after the last dose of IMC-A12 and CCI-779 (temsirolimus)\n  * Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately\n  * Nursing women must be willing to discontinue nursing; NOTE: breastfeeding should be discontinued if the mother is treated with CCI-779 and IMC-A12\n* Absolute neutrophil count >= 1,500/mcL\n* Hemoglobin >= 8.5 g/dL\n* Platelets >= 100,000/mcL\n* Total bilirubin =< 1.5 X institutional upper limit of normal (ULN)\n* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN (=< 5 X institutional ULN if liver function test [LFT] elevations due to liver metastases)\n* Creatinine =< 1.5 X institutional ULN OR creatinine clearance >= 60 mL/min/1.73^2 for patients with creatinine > institutional ULN\n* Fasting serum cholesterol =< 350 mg/dL (9.0 mmol/L)\n* Fasting triglycerides =< 400 mg/dL (4.56 mmol/L)\n* Albumin >= 3.4 mg/dL\n* Fasting or non fasting serum glucose < 120 mg/dL\n* Hemoglobin A1c (HbA1c) (for all patients with a history of diabetes mellitus) < 8%\n* Phase I only: Any number of prior therapy regimens is allowed\n* Phase II only: Measurable disease is required for the Phase II portion of the study; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques (computed tomography [CT], magnetic resonance imaging [MRI], x-ray) or as >= 10 mm with spiral CT scan\n* Phase II only: =< two and at least one prior chemotherapy regimens in the setting of metastatic or locally recurrent (stage IV chest wall involvement) disease are required\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Phase I patients only: Patients with base line diabetes requiring oral hypoglycemics or insulin\n* Phase II patients only: Poorly controlled diabetes mellitus; NOTE: patients with a history of diabetes mellitus on oral hypoglycemics or insulin are allowed to participate, provided that their fasting blood glucose is < 120 mg/dL and that they are on a stable dietary or therapeutic regimen for this condition\n* Any of the following:\n\n  * Pregnant women\n  * Nursing women\n  * Men or women of childbearing potential who are unwilling to employ adequate contraception (hormonal agents are not allowed and oral contraceptives are not acceptable for contraception)\n* Receiving hormonal agents used for the treatment of breast cancer with the exception that premenopausal women who have been on a gonadotropin-releasing hormone (GnRH) agonist and subsequently progressed may, at the discretion of the treating physician, continue on the GnRH agonist\n* Any of the following prior therapies:\n\n  * Systemic anti-cancer therapy =< 3 weeks prior to registration\n  * Radiation therapy =< 2 weeks prior to registration\n* Prior invasive non-breast malignancy, except for adequately treated basal or squamous cell carcinoma of the skin or other cancer from which the patient has been disease free for >= 5 years\n* Known hypersensitivity reactions to macrolide antibiotics (such as erythromycin, clarithromycin, and azithromycin); allergic reactions attributed to compounds of similar chemical or biologic composition to IMC-A12, or temsirolimus\n* Prior treatment with agents targeting the insulin-like growth factor-I receptor (IGF-IR)/insulin-like growth factors (IGFs) or phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PI3K)/v-akt murine thymoma viral oncogene homolog 1 (Akt)/mechanistic target of rapamycin (mTOR) pathway\n* Receiving any other investigational agents or herbal preparations\n* Patients may not be taking oral corticosteroids except for replacement for adrenal insufficiency\n* Uncontrolled brain metastases; Note: brain metastases are not permitted on study unless the metastases have been treated by surgery or radiotherapy, and the patient has been neurologically stable and off of steroids for >= 12 weeks\n* Known human immunodeficiency virus (HIV)-positive patients who have cluster of differentiation (CD)4 counts below the normal range or who are on anti-retroviral therapy that may interfere with the metabolism of temsirolimus\n* Uncontrolled intercurrent illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Symptomatic congestive heart failure\n  * Unstable angina pectoris\n  * Uncontrolled symptomatic cardiac arrhythmia\n  * Psychiatric illness/social situations that would limit compliance with study requirements\n* Receiving enzyme-inducing antiepileptic drugs (EIAEDs; e.g., phenytoin, carbamazepine, phenobarbital) or any other cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducer such as rifampin or St. John's wort",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Histologically confirmed diagnosis of breast cancer with diagnosis of metastatic or locally recurrent disease (locally recurrent disease should be stage IV e.g. chest wall involvement)",
            "criterions": [
                {
                    "exact_snippets": "Histologically confirmed diagnosis of breast cancer",
                    "criterion": "breast cancer diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": "histologically confirmed"
                        }
                    ]
                },
                {
                    "exact_snippets": "diagnosis of metastatic or locally recurrent disease",
                    "criterion": "disease status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "metastatic",
                                "locally recurrent"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "locally recurrent disease should be stage IV",
                    "criterion": "locally recurrent disease stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "IV"
                        }
                    ]
                },
                {
                    "exact_snippets": "chest wall involvement",
                    "criterion": "chest wall involvement",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 (Karnofsky >= 80%)",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Karnofsky >= 80%",
                    "criterion": "Karnofsky performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 80,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Life expectancy of > 12 weeks",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy of > 12 weeks",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Capable of understanding investigational nature, potential risks and benefits of the study and able to provide written informed consent",
            "criterions": [
                {
                    "exact_snippets": "Capable of understanding investigational nature, potential risks and benefits of the study",
                    "criterion": "understanding of study",
                    "requirements": [
                        {
                            "requirement_type": "capability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "able to provide written informed consent",
                    "criterion": "ability to provide consent",
                    "requirements": [
                        {
                            "requirement_type": "capability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Negative serum pregnancy test =< 7 days of registration for women of childbearing potential:",
            "criterions": [
                {
                    "exact_snippets": "Negative serum pregnancy test",
                    "criterion": "serum pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "=< 7 days of registration",
                    "criterion": "timing of test",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 7,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "women of childbearing potential",
                    "criterion": "gender and reproductive status",
                    "requirements": [
                        {
                            "requirement_type": "applicability",
                            "expected_value": "women of childbearing potential"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study therapy and for 3 months after the last dose of IMC-A12 and CCI-779 (temsirolimus)",
            "criterions": [
                {
                    "exact_snippets": "Women of child-bearing potential",
                    "criterion": "women of child-bearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "men must agree to use adequate contraception",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "adequate contraception (hormonal or barrier method of birth control; abstinence)",
                    "criterion": "contraception method",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "hormonal",
                                "barrier",
                                "abstinence"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "for the duration of study therapy and for 3 months after the last dose of IMC-A12 and CCI-779 (temsirolimus)",
                    "criterion": "contraception duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "for the duration of study therapy and for 3 months after the last dose of IMC-A12 and CCI-779 (temsirolimus)"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately",
            "criterions": [
                {
                    "exact_snippets": "Should a woman become pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "suspect she is pregnant",
                    "criterion": "suspected pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Nursing women must be willing to discontinue nursing; NOTE: breastfeeding should be discontinued if the mother is treated with CCI-779 and IMC-A12",
            "criterions": [
                {
                    "exact_snippets": "Nursing women must be willing to discontinue nursing",
                    "criterion": "nursing women",
                    "requirements": [
                        {
                            "requirement_type": "willingness to discontinue nursing",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "breastfeeding should be discontinued if the mother is treated with CCI-779 and IMC-A12",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "discontinuation",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "treatment",
                            "expected_value": [
                                "CCI-779",
                                "IMC-A12"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Absolute neutrophil count >= 1,500/mcL",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count >= 1,500/mcL",
                    "criterion": "absolute neutrophil count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1500,
                                "unit": "mcL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hemoglobin >= 8.5 g/dL",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin >= 8.5 g/dL",
                    "criterion": "hemoglobin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 8.5,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelets >= 100,000/mcL",
            "criterions": [
                {
                    "exact_snippets": "Platelets >= 100,000/mcL",
                    "criterion": "platelets",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100000,
                                "unit": "mcL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Total bilirubin =< 1.5 X institutional upper limit of normal (ULN)",
            "criterions": [
                {
                    "exact_snippets": "Total bilirubin =< 1.5 X institutional upper limit of normal (ULN)",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "X institutional upper limit of normal (ULN)"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN (=< 5 X institutional ULN if liver function test [LFT] elevations due to liver metastases)",
            "criterions": [
                {
                    "exact_snippets": "Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) ... =< 3 x institutional ULN (=< 5 X institutional ULN if liver function test [LFT] elevations due to liver metastases)",
                    "criterion": "Aspartate aminotransferase (AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "x institutional ULN"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "x institutional ULN"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "condition",
                            "expected_value": "if liver function test [LFT] elevations due to liver metastases"
                        }
                    ]
                },
                {
                    "exact_snippets": "alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN (=< 5 X institutional ULN if liver function test [LFT] elevations due to liver metastases)",
                    "criterion": "alanine aminotransferase (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "x institutional ULN"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "x institutional ULN"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "condition",
                            "expected_value": "if liver function test [LFT] elevations due to liver metastases"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Creatinine =< 1.5 X institutional ULN OR creatinine clearance >= 60 mL/min/1.73^2 for patients with creatinine > institutional ULN",
            "criterions": [
                {
                    "exact_snippets": "Creatinine =< 1.5 X institutional ULN",
                    "criterion": "creatinine",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "X institutional ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "creatinine clearance >= 60 mL/min/1.73^2",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 60,
                                "unit": "mL/min/1.73^2"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Fasting serum cholesterol =< 350 mg/dL (9.0 mmol/L)",
            "criterions": [
                {
                    "exact_snippets": "Fasting serum cholesterol =< 350 mg/dL (9.0 mmol/L)",
                    "criterion": "fasting serum cholesterol",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 350,
                                "unit": "mg/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Fasting triglycerides =< 400 mg/dL (4.56 mmol/L)",
            "criterions": [
                {
                    "exact_snippets": "Fasting triglycerides =< 400 mg/dL (4.56 mmol/L)",
                    "criterion": "fasting triglycerides",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 400,
                                "unit": "mg/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Albumin >= 3.4 mg/dL",
            "criterions": [
                {
                    "exact_snippets": "Albumin >= 3.4 mg/dL",
                    "criterion": "albumin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3.4,
                                "unit": "mg/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Fasting or non fasting serum glucose < 120 mg/dL",
            "criterions": [
                {
                    "exact_snippets": "Fasting or non fasting serum glucose < 120 mg/dL",
                    "criterion": "serum glucose",
                    "requirements": [
                        {
                            "requirement_type": "state",
                            "expected_value": [
                                "fasting",
                                "non fasting"
                            ]
                        },
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 120,
                                "unit": "mg/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hemoglobin A1c (HbA1c) (for all patients with a history of diabetes mellitus) < 8%",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin A1c (HbA1c) ... < 8%",
                    "criterion": "Hemoglobin A1c (HbA1c)",
                    "requirements": [
                        {
                            "requirement_type": "history of diabetes mellitus",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 8,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Phase I only: Any number of prior therapy regimens is allowed",
            "criterions": [
                {
                    "exact_snippets": "Phase I only: Any number of prior therapy regimens is allowed",
                    "criterion": "prior therapy regimens",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": "any number"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Phase II only: Measurable disease is required for the Phase II portion of the study; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques (computed tomography [CT], magnetic resonance imaging [MRI], x-ray) or as >= 10 mm with spiral CT scan",
            "criterions": [
                {
                    "exact_snippets": "Measurable disease is required",
                    "criterion": "measurable disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques (computed tomography [CT], magnetic resonance imaging [MRI], x-ray)",
                    "criterion": "lesion size with conventional techniques",
                    "requirements": [
                        {
                            "requirement_type": "size",
                            "expected_value": {
                                "operator": ">=",
                                "value": 20,
                                "unit": "mm"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) ... or as >= 10 mm with spiral CT scan",
                    "criterion": "lesion size with spiral CT scan",
                    "requirements": [
                        {
                            "requirement_type": "size",
                            "expected_value": {
                                "operator": ">=",
                                "value": 10,
                                "unit": "mm"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "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 18 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 18 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "* Phase I patients only: Patients with base line diabetes requiring oral hypoglycemics or insulin",
            "criterions": [
                {
                    "exact_snippets": "Phase I patients only",
                    "criterion": "trial phase",
                    "requirements": [
                        {
                            "requirement_type": "phase",
                            "expected_value": "I"
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients with base line diabetes",
                    "criterion": "diabetes",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "requiring oral hypoglycemics or insulin",
                    "criterion": "diabetes treatment",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": [
                                "oral hypoglycemics",
                                "insulin"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Phase II patients only: Poorly controlled diabetes mellitus; NOTE: patients with a history of diabetes mellitus on oral hypoglycemics or insulin are allowed to participate, provided that their fasting blood glucose is < 120 mg/dL and that they are on a stable dietary or therapeutic regimen for this condition",
            "criterions": [
                {
                    "exact_snippets": "Phase II patients only",
                    "criterion": "trial phase",
                    "requirements": [
                        {
                            "requirement_type": "phase",
                            "expected_value": "II"
                        }
                    ]
                },
                {
                    "exact_snippets": "Poorly controlled diabetes mellitus",
                    "criterion": "diabetes mellitus control",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "poorly controlled"
                        }
                    ]
                },
                {
                    "exact_snippets": "patients with a history of diabetes mellitus on oral hypoglycemics or insulin are allowed to participate",
                    "criterion": "diabetes mellitus treatment",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": [
                                "oral hypoglycemics",
                                "insulin"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "fasting blood glucose is < 120 mg/dL",
                    "criterion": "fasting blood glucose",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 120,
                                "unit": "mg/dL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "stable dietary or therapeutic regimen for this condition",
                    "criterion": "dietary or therapeutic regimen stability",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": "stable"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant women",
            "criterions": [
                {
                    "exact_snippets": "Pregnant women",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Nursing women",
            "criterions": [
                {
                    "exact_snippets": "Nursing women",
                    "criterion": "nursing status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "nursing"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Men or women of childbearing potential who are unwilling to employ adequate contraception (hormonal agents are not allowed and oral contraceptives are not acceptable for contraception)",
            "criterions": [
                {
                    "exact_snippets": "Men or women of childbearing potential",
                    "criterion": "childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "unwilling to employ adequate contraception",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "hormonal agents are not allowed",
                    "criterion": "hormonal agents",
                    "requirements": [
                        {
                            "requirement_type": "allowance",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "oral contraceptives are not acceptable for contraception",
                    "criterion": "oral contraceptives",
                    "requirements": [
                        {
                            "requirement_type": "acceptability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Receiving hormonal agents used for the treatment of breast cancer with the exception that premenopausal women who have been on a gonadotropin-releasing hormone (GnRH) agonist and subsequently progressed may, at the discretion of the treating physician, continue on the GnRH agonist",
            "criterions": [
                {
                    "exact_snippets": "Receiving hormonal agents used for the treatment of breast cancer",
                    "criterion": "hormonal agents for breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "premenopausal women who have been on a gonadotropin-releasing hormone (GnRH) agonist and subsequently progressed",
                    "criterion": "GnRH agonist treatment progression",
                    "requirements": [
                        {
                            "requirement_type": "progression",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any of the following prior therapies:",
            "criterions": [
                {
                    "exact_snippets": "Any of the following prior therapies",
                    "criterion": "prior therapies",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Systemic anti-cancer therapy =< 3 weeks prior to registration",
            "criterions": [
                {
                    "exact_snippets": "Systemic anti-cancer therapy =< 3 weeks prior to registration",
                    "criterion": "systemic anti-cancer therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Radiation therapy =< 2 weeks prior to registration",
            "criterions": [
                {
                    "exact_snippets": "Radiation therapy =< 2 weeks prior to registration",
                    "criterion": "radiation therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior invasive non-breast malignancy, except for adequately treated basal or squamous cell carcinoma of the skin or other cancer from which the patient has been disease free for >= 5 years",
            "criterions": [
                {
                    "exact_snippets": "Prior invasive non-breast malignancy",
                    "criterion": "prior invasive non-breast malignancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "adequately treated basal or squamous cell carcinoma of the skin",
                    "criterion": "adequately treated basal or squamous cell carcinoma of the skin",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "other cancer from which the patient has been disease free for >= 5 years",
                    "criterion": "disease-free status from other cancer",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 5,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known hypersensitivity reactions to macrolide antibiotics (such as erythromycin, clarithromycin, and azithromycin); allergic reactions attributed to compounds of similar chemical or biologic composition to IMC-A12, or temsirolimus",
            "criterions": [
                {
                    "exact_snippets": "Known hypersensitivity reactions to macrolide antibiotics (such as erythromycin, clarithromycin, and azithromycin)",
                    "criterion": "hypersensitivity to macrolide antibiotics",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "allergic reactions attributed to compounds of similar chemical or biologic composition to IMC-A12",
                    "criterion": "allergic reactions to compounds similar to IMC-A12",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "allergic reactions attributed to compounds of similar chemical or biologic composition to ... temsirolimus",
                    "criterion": "allergic reactions to compounds similar to temsirolimus",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior treatment with agents targeting the insulin-like growth factor-I receptor (IGF-IR)/insulin-like growth factors (IGFs) or phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PI3K)/v-akt murine thymoma viral oncogene homolog 1 (Akt)/mechanistic target of rapamycin (mTOR) pathway",
            "criterions": [
                {
                    "exact_snippets": "Prior treatment with agents targeting the insulin-like growth factor-I receptor (IGF-IR)/insulin-like growth factors (IGFs)",
                    "criterion": "prior treatment with IGF-IR/IGFs targeting agents",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior treatment with agents targeting the ... phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PI3K)/v-akt murine thymoma viral oncogene homolog 1 (Akt)/mechanistic target of rapamycin (mTOR) pathway",
                    "criterion": "prior treatment with PI3K/Akt/mTOR pathway targeting agents",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Receiving any other investigational agents or herbal preparations",
            "criterions": [
                {
                    "exact_snippets": "Receiving any other investigational agents",
                    "criterion": "investigational agents",
                    "requirements": [
                        {
                            "requirement_type": "receiving",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Receiving any other ... herbal preparations",
                    "criterion": "herbal preparations",
                    "requirements": [
                        {
                            "requirement_type": "receiving",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients may not be taking oral corticosteroids except for replacement for adrenal insufficiency",
            "criterions": [
                {
                    "exact_snippets": "Patients may not be taking oral corticosteroids",
                    "criterion": "oral corticosteroids",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "except for replacement for adrenal insufficiency",
                    "criterion": "adrenal insufficiency",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "replacement"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uncontrolled brain metastases; Note: brain metastases are not permitted on study unless the metastases have been treated by surgery or radiotherapy, and the patient has been neurologically stable and off of steroids for >= 12 weeks",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled brain metastases",
                    "criterion": "brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "brain metastases are not permitted ... unless the metastases have been treated by surgery or radiotherapy",
                    "criterion": "brain metastases treatment",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": [
                                "surgery",
                                "radiotherapy"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "patient has been neurologically stable",
                    "criterion": "neurological stability",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "off of steroids for >= 12 weeks",
                    "criterion": "steroid use",
                    "requirements": [
                        {
                            "requirement_type": "duration off steroids",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known human immunodeficiency virus (HIV)-positive patients who have cluster of differentiation (CD)4 counts below the normal range or who are on anti-retroviral therapy that may interfere with the metabolism of temsirolimus",
            "criterions": [
                {
                    "exact_snippets": "Known human immunodeficiency virus (HIV)-positive patients",
                    "criterion": "HIV status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "cluster of differentiation (CD)4 counts below the normal range",
                    "criterion": "CD4 count",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 0,
                                        "unit": "normal range"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "on anti-retroviral therapy that may interfere with the metabolism of temsirolimus",
                    "criterion": "anti-retroviral therapy",
                    "requirements": [
                        {
                            "requirement_type": "interference with metabolism of temsirolimus",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uncontrolled intercurrent illness including, but not limited to:",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled intercurrent illness",
                    "criterion": "intercurrent illness",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "uncontrolled"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Ongoing or active infection",
            "criterions": [
                {
                    "exact_snippets": "Ongoing or active infection",
                    "criterion": "infection",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "ongoing",
                                "active"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Symptomatic congestive heart failure",
            "criterions": [
                {
                    "exact_snippets": "Symptomatic congestive heart failure",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Unstable angina pectoris",
            "criterions": [
                {
                    "exact_snippets": "Unstable angina pectoris",
                    "criterion": "angina pectoris",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": "unstable"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uncontrolled symptomatic cardiac arrhythmia",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled symptomatic cardiac arrhythmia",
                    "criterion": "cardiac arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Psychiatric illness/social situations that would limit compliance with study requirements",
            "criterions": [
                {
                    "exact_snippets": "Psychiatric illness",
                    "criterion": "psychiatric illness",
                    "requirements": [
                        {
                            "requirement_type": "impact on compliance",
                            "expected_value": "limit compliance with study requirements"
                        }
                    ]
                },
                {
                    "exact_snippets": "social situations",
                    "criterion": "social situations",
                    "requirements": [
                        {
                            "requirement_type": "impact on compliance",
                            "expected_value": "limit compliance with study requirements"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Receiving enzyme-inducing antiepileptic drugs (EIAEDs; e.g., phenytoin, carbamazepine, phenobarbital) or any other cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducer such as rifampin or St. John's wort",
            "criterions": [
                {
                    "exact_snippets": "Receiving enzyme-inducing antiepileptic drugs (EIAEDs; e.g., phenytoin, carbamazepine, phenobarbital)",
                    "criterion": "enzyme-inducing antiepileptic drugs (EIAEDs)",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Receiving ... any other cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducer such as rifampin or St. John's wort",
                    "criterion": "cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "* Phase II only: =< two and at least one prior chemotherapy regimens in the setting of metastatic or locally recurrent (stage IV chest wall involvement) disease are required",
            "criterions": [
                {
                    "exact_snippets": "= < two and at least one prior chemotherapy regimens",
                    "criterion": "prior chemotherapy regimens",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": ">=",
                                        "value": 1,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "metastatic or locally recurrent (stage IV chest wall involvement) disease",
                    "criterion": "disease status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "metastatic",
                                "locally recurrent (stage IV chest wall involvement)"
                            ]
                        }
                    ]
                }
            ]
        }
    ],
    "failed_exclusion": [
        {
            "line": "* Any of the following:",
            "criterions": []
        }
    ],
    "failed_miscellaneous": []
}