{
    "info": {
        "nct_id": "NCT01637194",
        "official_title": "A Phase I Evaluation of Cetuximab and RAD001 in Patients With Solid Tumors",
        "inclusion_criteria": "* Patients must have histologically-confirmed advanced solid tumors\n* Patients who are refractory to standard therapy; patients with metastatic, irinotecan-refractory colon cancer, or recurrent/metastatic head and neck cancer may enroll, as cetuximab monotherapy is among the standard options for such patients; patients with locally advanced, treatment-naïve head and neck cancer who are candidates for radiation with cetuximab are not eligible, as radiation provides them a survival benefit, and the number of projected cetuximab doses would be only seven\n* Development of new lesions or an increase in preexisting lesions on bone scintigraphy, computed tomography (CT), magnetic resonance imaging (MRI) or by physical examination; patients in whom the sole criterion for progression is an increase in a biochemical marker, e.g., carcinoembryonic antigen (CEA), or an increase in symptoms, are not eligible\n* No radiotherapy (unless palliative), treatment with cytotoxic agents, or treatment with biologic agents =< 3 weeks prior to registration on this study (6 weeks for mitomycin or nitrosoureas); >= 2 weeks must have elapsed from any prior surgery or hormonal therapy; patients must have fully recovered from the acute toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment); patients with persisting, stable chronic toxicities from prior treatment =< grade 1 are eligible\n* Eastern Cooperative Oncology Group (ECOG) performance status =<2 (Karnofsky >= 60%)\n* Life expectancy of > 3 months\n* Hemoglobin >= 9 g/dL\n* Leukocytes >=3 K/mm^3\n* Absolute neutrophil count >= 1.5 K/mm^3\n* Platelets >= 100 K/mm^3\n* Total bilirubin within institutional normal limits\n* Hepatitis B panel negative\n* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal (ULN)\n* Creatinine within 1.5 x ULN OR creatinine clearance >= 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal\n* Women of child-bearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; complete abstinence) prior to study entry and for the duration of study participation and for 3 months after the conclusion of study therapy, and must have a negative serum or urine pregnancy test =< 7 days prior to registration; pregnant and nursing patients are excluded because the side effects of the combination of cetuximab and RAD001 on a fetus or nursing child are unknown; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; sexually active men must also use appropriate contraception method and should not father a child while receiving therapy during this study\n* Ability to understand and the willingness to sign a written informed consent document\n* Fasting serum cholesterol < 350 mg/d L and triglycerides < 400 mg/d L\n* Able and willing to undergo pharmacokinetic (PK) and pharmacodynamic (PD) testing as outlined in this protocol; if however the tumor is not amenable to the PD requirements of the protocol, the patient must be willing and able to undergo skin biopsy\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Chronic treatment with systemic steroids or another immunosuppressive agent\n* Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases\n* Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)\n* Patients with an active, bleeding diathesis or on therapeutic anticoagulation (except low dose coumadin)\n* Patients may not have received prior cetuximab therapy\n* Patients may not be receiving any other investigational agents; in addition, patients must not have received investigational treatment =< 30 days prior to registration\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study\n* Patients with chronic active hepatitis B or recent hepatitis B infection (hepatitis B surface antigen [HepB sAg] or immunoglobulin M [IgM] antibody to hepatitis B core antigen [IgM antiBc] positive) are ineligible because these patients are at increased risk of reactivation of the hepatitis B virus which may be fatal due to the immunosuppressive properties of RAD001\n* Known human immunodeficiency virus (HIV)-positive patients are ineligible because these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy and the potential pharmacokinetic interaction between antiretroviral therapy and the investigational agents\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, oxygen dependent pulmonary disease or psychiatric illness/social situations that would limit compliance with study requirements; other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension, severe malnutrition, active ischemic heart disease, myocardial infarction within six months, chronic liver or renal disease, active upper gastrointestinal [GI] tract ulceration)\n* All WOCBP MUST have a negative pregnancy test =< 7 days prior to registration; if the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Patients must have histologically-confirmed advanced solid tumors",
            "criterions": [
                {
                    "exact_snippets": "histologically-confirmed advanced solid tumors",
                    "criterion": "solid tumors",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "histologically-confirmed"
                        },
                        {
                            "requirement_type": "stage",
                            "expected_value": "advanced"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who are refractory to standard therapy; patients with metastatic, irinotecan-refractory colon cancer, or recurrent/metastatic head and neck cancer may enroll, as cetuximab monotherapy is among the standard options for such patients; patients with locally advanced, treatment-naïve head and neck cancer who are candidates for radiation with cetuximab are not eligible, as radiation provides them a survival benefit, and the number of projected cetuximab doses would be only seven",
            "criterions": [
                {
                    "exact_snippets": "Patients who are refractory to standard therapy",
                    "criterion": "refractory to standard therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "patients with metastatic, irinotecan-refractory colon cancer",
                    "criterion": "metastatic, irinotecan-refractory colon cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "recurrent/metastatic head and neck cancer",
                    "criterion": "recurrent/metastatic head and neck cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "patients with locally advanced, treatment-naïve head and neck cancer who are candidates for radiation with cetuximab are not eligible",
                    "criterion": "locally advanced, treatment-naïve head and neck cancer",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Development of new lesions or an increase in preexisting lesions on bone scintigraphy, computed tomography (CT), magnetic resonance imaging (MRI) or by physical examination; patients in whom the sole criterion for progression is an increase in a biochemical marker, e.g., carcinoembryonic antigen (CEA), or an increase in symptoms, are not eligible",
            "criterions": [
                {
                    "exact_snippets": "Development of new lesions",
                    "criterion": "new lesions",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "increase in preexisting lesions",
                    "criterion": "preexisting lesions",
                    "requirements": [
                        {
                            "requirement_type": "change",
                            "expected_value": "increase"
                        }
                    ]
                },
                {
                    "exact_snippets": "bone scintigraphy",
                    "criterion": "bone scintigraphy",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "used for detection"
                        }
                    ]
                },
                {
                    "exact_snippets": "computed tomography (CT)",
                    "criterion": "computed tomography (CT)",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "used for detection"
                        }
                    ]
                },
                {
                    "exact_snippets": "magnetic resonance imaging (MRI)",
                    "criterion": "magnetic resonance imaging (MRI)",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "used for detection"
                        }
                    ]
                },
                {
                    "exact_snippets": "physical examination",
                    "criterion": "physical examination",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "used for detection"
                        }
                    ]
                },
                {
                    "exact_snippets": "patients in whom the sole criterion for progression is an increase in a biochemical marker, e.g., carcinoembryonic antigen (CEA), or an increase in symptoms, are not eligible",
                    "criterion": "biochemical marker increase",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "patients in whom the sole criterion for progression is an increase in a biochemical marker, e.g., carcinoembryonic antigen (CEA), or an increase in symptoms, are not eligible",
                    "criterion": "symptoms increase",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No radiotherapy (unless palliative), treatment with cytotoxic agents, or treatment with biologic agents =< 3 weeks prior to registration on this study (6 weeks for mitomycin or nitrosoureas); >= 2 weeks must have elapsed from any prior surgery or hormonal therapy; patients must have fully recovered from the acute toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment); patients with persisting, stable chronic toxicities from prior treatment =< grade 1 are eligible",
            "criterions": [
                {
                    "exact_snippets": "No radiotherapy (unless palliative) ... =< 3 weeks prior to registration",
                    "criterion": "radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "treatment with cytotoxic agents ... =< 3 weeks prior to registration",
                    "criterion": "treatment with cytotoxic agents",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "treatment with biologic agents =< 3 weeks prior to registration",
                    "criterion": "treatment with biologic agents",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "6 weeks for mitomycin or nitrosoureas",
                    "criterion": "treatment with mitomycin or nitrosoureas",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 6,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": ">= 2 weeks must have elapsed from any prior surgery or hormonal therapy",
                    "criterion": "prior surgery or hormonal therapy",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 2,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "patients must have fully recovered from the acute toxicities of any prior treatment",
                    "criterion": "recovery from acute toxicities",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "fully recovered"
                        }
                    ]
                },
                {
                    "exact_snippets": "patients with persisting, stable chronic toxicities from prior treatment =< grade 1 are eligible",
                    "criterion": "chronic toxicities from prior treatment",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 1,
                                        "unit": "grade"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Eastern Cooperative Oncology Group (ECOG) performance status =<2 (Karnofsky >= 60%)",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status =<2",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "performance status",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Karnofsky >= 60%",
                    "criterion": "Karnofsky performance status",
                    "requirements": [
                        {
                            "requirement_type": "performance status",
                            "expected_value": {
                                "operator": ">=",
                                "value": 60,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Life expectancy of > 3 months",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy of > 3 months",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hemoglobin >= 9 g/dL",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin >= 9 g/dL",
                    "criterion": "hemoglobin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Leukocytes >=3 K/mm^3",
            "criterions": [
                {
                    "exact_snippets": "Leukocytes >=3 K/mm^3",
                    "criterion": "leukocytes",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "K/mm^3"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Absolute neutrophil count >= 1.5 K/mm^3",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count >= 1.5 K/mm^3",
                    "criterion": "absolute neutrophil count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "K/mm^3"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelets >= 100 K/mm^3",
            "criterions": [
                {
                    "exact_snippets": "Platelets >= 100 K/mm^3",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100,
                                "unit": "K/mm^3"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Total bilirubin within institutional normal limits",
            "criterions": [
                {
                    "exact_snippets": "Total bilirubin within institutional normal limits",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": "within institutional normal limits"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hepatitis B panel negative",
            "criterions": [
                {
                    "exact_snippets": "Hepatitis B panel negative",
                    "criterion": "Hepatitis B panel",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal (ULN)",
            "criterions": [
                {
                    "exact_snippets": "Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) ... =< 2.5 X institutional upper limit of normal (ULN)",
                    "criterion": "aspartate aminotransferase (AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "X institutional upper limit of normal (ULN)"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alanine aminotransferase (ALT)(serum glutamic pyruvate transaminase [SGPT]) ... =< 2.5 X institutional upper limit of normal (ULN)",
                    "criterion": "alanine aminotransferase (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "X institutional upper limit of normal (ULN)"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Creatinine within 1.5 x ULN OR creatinine clearance >= 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal",
            "criterions": [
                {
                    "exact_snippets": "Creatinine within 1.5 x ULN",
                    "criterion": "creatinine",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "creatinine clearance >= 50 mL/min/1.73 m^2",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "mL/min/1.73 m^2"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women of child-bearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; complete abstinence) prior to study entry and for the duration of study participation and for 3 months after the conclusion of study therapy, and must have a negative serum or urine pregnancy test =< 7 days prior to registration; pregnant and nursing patients are excluded because the side effects of the combination of cetuximab and RAD001 on a fetus or nursing child are unknown; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; sexually active men must also use appropriate contraception method and should not father a child while receiving therapy during this study",
            "criterions": [
                {
                    "exact_snippets": "Women of child-bearing potential (WOCBP)",
                    "criterion": "women of child-bearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must agree to use adequate contraception (hormonal or barrier method of birth control; complete abstinence)",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must have a negative serum or urine pregnancy test =< 7 days prior to registration",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": {
                                "operator": "<=",
                                "value": 7,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "pregnant and nursing patients are excluded",
                    "criterion": "pregnancy or nursing",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "sexually active men must also use appropriate contraception method",
                    "criterion": "contraception use for sexually active men",
                    "requirements": [
                        {
                            "requirement_type": "requirement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Ability to understand and the willingness to sign a written informed consent document",
            "criterions": [
                {
                    "exact_snippets": "Ability to understand",
                    "criterion": "cognitive ability",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "willingness to sign a written informed consent document",
                    "criterion": "willingness to consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Fasting serum cholesterol < 350 mg/d L and triglycerides < 400 mg/d L",
            "criterions": [
                {
                    "exact_snippets": "Fasting serum cholesterol < 350 mg/d L",
                    "criterion": "fasting serum cholesterol",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 350,
                                "unit": "mg/dL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "triglycerides < 400 mg/d L",
                    "criterion": "triglycerides",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 400,
                                "unit": "mg/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Able and willing to undergo pharmacokinetic (PK) and pharmacodynamic (PD) testing as outlined in this protocol; if however the tumor is not amenable to the PD requirements of the protocol, the patient must be willing and able to undergo skin biopsy",
            "criterions": [
                {
                    "exact_snippets": "Able and willing to undergo pharmacokinetic (PK) ... testing",
                    "criterion": "pharmacokinetic (PK) testing",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Able and willing to undergo ... pharmacodynamic (PD) testing",
                    "criterion": "pharmacodynamic (PD) testing",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "tumor is not amenable to the PD requirements",
                    "criterion": "tumor amenability to PD requirements",
                    "requirements": [
                        {
                            "requirement_type": "amenability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "willing and able to undergo skin biopsy",
                    "criterion": "skin biopsy",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "ability",
                            "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 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": "* Chronic treatment with systemic steroids or another immunosuppressive agent",
            "criterions": [
                {
                    "exact_snippets": "Chronic treatment with systemic steroids",
                    "criterion": "chronic treatment with systemic steroids",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "another immunosuppressive agent",
                    "criterion": "treatment with another immunosuppressive agent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled brain or leptomeningeal metastases",
                    "criterion": "brain or leptomeningeal metastases",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        }
                    ]
                },
                {
                    "exact_snippets": "patients who continue to require glucocorticoids for brain or leptomeningeal metastases",
                    "criterion": "glucocorticoid requirement for brain or leptomeningeal metastases",
                    "requirements": [
                        {
                            "requirement_type": "requirement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)",
            "criterions": [
                {
                    "exact_snippets": "Impairment of gastrointestinal function or gastrointestinal disease",
                    "criterion": "gastrointestinal function or disease",
                    "requirements": [
                        {
                            "requirement_type": "impairment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ulcerative disease",
                    "criterion": "ulcerative disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled nausea",
                    "criterion": "nausea",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "vomiting",
                    "criterion": "vomiting",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "diarrhea",
                    "criterion": "diarrhea",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "malabsorption syndrome",
                    "criterion": "malabsorption syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "small bowel resection",
                    "criterion": "small bowel resection",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with an active, bleeding diathesis or on therapeutic anticoagulation (except low dose coumadin)",
            "criterions": [
                {
                    "exact_snippets": "Patients with an active, bleeding diathesis",
                    "criterion": "bleeding diathesis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "on therapeutic anticoagulation (except low dose coumadin)",
                    "criterion": "therapeutic anticoagulation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients may not have received prior cetuximab therapy",
            "criterions": [
                {
                    "exact_snippets": "Patients may not have received prior cetuximab therapy",
                    "criterion": "prior cetuximab therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients may not be receiving any other investigational agents; in addition, patients must not have received investigational treatment =< 30 days prior to registration",
            "criterions": [
                {
                    "exact_snippets": "Patients may not be receiving any other investigational agents",
                    "criterion": "receiving investigational agents",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "patients must not have received investigational treatment =< 30 days prior to registration",
                    "criterion": "investigational treatment received",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 30,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study",
            "criterions": [
                {
                    "exact_snippets": "History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study",
                    "criterion": "allergic reactions",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "attribution",
                            "expected_value": "compounds of similar chemical or biologic composition to agents used in study"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with chronic active hepatitis B or recent hepatitis B infection (hepatitis B surface antigen [HepB sAg] or immunoglobulin M [IgM] antibody to hepatitis B core antigen [IgM antiBc] positive) are ineligible because these patients are at increased risk of reactivation of the hepatitis B virus which may be fatal due to the immunosuppressive properties of RAD001",
            "criterions": [
                {
                    "exact_snippets": "chronic active hepatitis B",
                    "criterion": "chronic active hepatitis B",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "recent hepatitis B infection",
                    "criterion": "recent hepatitis B infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "hepatitis B surface antigen [HepB sAg] ... positive",
                    "criterion": "hepatitis B surface antigen [HepB sAg]",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "immunoglobulin M [IgM] antibody to hepatitis B core antigen [IgM antiBc] positive",
                    "criterion": "immunoglobulin M [IgM] antibody to hepatitis B core antigen [IgM antiBc]",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known human immunodeficiency virus (HIV)-positive patients are ineligible because these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy and the potential pharmacokinetic interaction between antiretroviral therapy and the investigational agents",
            "criterions": [
                {
                    "exact_snippets": "Known human immunodeficiency virus (HIV)-positive",
                    "criterion": "HIV status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "negative"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, oxygen dependent pulmonary disease or psychiatric illness/social situations that would limit compliance with study requirements; other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension, severe malnutrition, active ischemic heart disease, myocardial infarction within six months, chronic liver or renal disease, active upper gastrointestinal [GI] tract ulceration)",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection",
                    "criterion": "intercurrent illness",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "uncontrolled"
                        }
                    ]
                },
                {
                    "exact_snippets": "ongoing or active infection",
                    "criterion": "infection",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "ongoing",
                                "active"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "symptomatic congestive heart failure",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "symptoms",
                            "expected_value": "symptomatic"
                        }
                    ]
                },
                {
                    "exact_snippets": "unstable angina pectoris",
                    "criterion": "angina pectoris",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": "unstable"
                        }
                    ]
                },
                {
                    "exact_snippets": "cardiac arrhythmia",
                    "criterion": "cardiac arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "oxygen dependent pulmonary disease",
                    "criterion": "pulmonary disease",
                    "requirements": [
                        {
                            "requirement_type": "oxygen dependency",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "psychiatric illness/social situations that would limit compliance with study requirements",
                    "criterion": "psychiatric illness/social situations",
                    "requirements": [
                        {
                            "requirement_type": "impact on compliance",
                            "expected_value": "limit"
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled diabetes",
                    "criterion": "diabetes",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "uncontrolled"
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled hypertension",
                    "criterion": "hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "uncontrolled"
                        }
                    ]
                },
                {
                    "exact_snippets": "severe malnutrition",
                    "criterion": "malnutrition",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        }
                    ]
                },
                {
                    "exact_snippets": "active ischemic heart disease",
                    "criterion": "ischemic heart disease",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "active"
                        }
                    ]
                },
                {
                    "exact_snippets": "myocardial infarction within six months",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "chronic liver or renal disease",
                    "criterion": "liver or renal disease",
                    "requirements": [
                        {
                            "requirement_type": "chronicity",
                            "expected_value": "chronic"
                        }
                    ]
                },
                {
                    "exact_snippets": "active upper gastrointestinal [GI] tract ulceration",
                    "criterion": "upper gastrointestinal tract ulceration",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "active"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* All WOCBP MUST have a negative pregnancy test =< 7 days prior to registration; if the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study",
            "criterions": [
                {
                    "exact_snippets": "WOCBP MUST have a negative pregnancy test",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "pregnancy test =< 7 days prior to registration",
                    "criterion": "pregnancy test timing",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 7,
                                "unit": "days prior to registration"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}