{
    "info": {
        "nct_id": "NCT01579994",
        "official_title": "A Phase I Study of Crizotinib and Ganetespib (STA-9090) in ALK Positive Lung Cancers",
        "inclusion_criteria": "* Histologically or cytologically proven diagnosis confirmed at MSKCC of advanced lung adenocarcinoma that is locally advanced or metastatic (stage III/IV).\n* Positive for translocation or inversion events involving the ALK gene locus as determined standard methods (including but not limited to by FISH and IHC testing).\n* No prior treatment with crizotinib, but they may have received prior cytotoxic chemotherapy.\n* Age ≥ 18 years.\n* Measurable (RECIST 1.1) indicator lesion not previously irradiated.\n* Karnofsky Performance Status ≥ 70%\n* Able to take oral medications\n* A negative serum pregnancy test obtained within two weeks prior to administration of the experimental agents in all pre-menopausal women (last menstrual period ≤ 24 months ago).\n* All women of child bearing potential (WOCBP) and sexually active men must agree to use adequate methods of birth control throughout the study which include use of oral contraceptives with an additional barrier method, double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), Depo-Provera, partner vasectomy and/or tubal libation and total abstinence.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Prior crizotinib therapy\n* Inadequate recovery from any toxicity related to prior treatment (to Grade 1 or baseline).\n* Inadequate hematologic function defined as:\n\n  * Absolute neutrophil count (ANC) < 1,000 cells/mm³.\n  * Platelet count < 75,000/mm³\n  * Hemoglobin < 9.0g/dL.\n\nInadequate hepatic function defined by:\n\n* AST and/or ALT > 3x upper limited of normal (ULN).\n* Total bilirubin > 2x ULN.\n* Alkaline phosphatase > 3x ULN.\n* Patients with hepatic metastases may have ALT/AST ≤ 5x ULN.\n* Patients with hepatic and/or bone metastases may have an AP ≤ 5x ULN.\n* Inadequate renal function defined by serum creatinine > 2x ULN Uncontrolled systemic fungal, bacterial, viral or other infection (defined as exhibiting ongoing signs/symptoms related to infection without improvement, despite appropriate anti-infective medications or other treatment).\n* Patients with clinically active brain metastasis (requiring therapy with steroids or radiation therapy). Patients with clinically stable brain metastases (previously treated or untreated) for two weeks are eligible.\n* Significant cardiac disease (e.g. New York Heart Association (NYHA) Class 3 or 4; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty or coronary artery bypass graft (CABG) within the past 6 months; or uncontrolled atrial or ventricular cardiac arrhythmias).\n* Previously or current malignancies at other sites within the last 2 years, with the exception of adequately treated in situ carcinoma of the cervix, basal or squamous cell carcinoma of the skin, or prostate cancer that does not require active treatment per National Comprehensive Cancer Network (NCCN) guidelines.\n* Women who are pregnant or lactating\n* Use of drugs or food that are known potent CYP3A4 inhibitors (see Appendix C)\n* Use of drugs that are known potent CYP3A4 inducers (see Appendix D)\n* Any other condition that, in the opinion of the Investigator, may compromise the safety, compliance of the patient, or would preclude the patient from successful completion of the study.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Histologically or cytologically proven diagnosis confirmed at MSKCC of advanced lung adenocarcinoma that is locally advanced or metastatic (stage III/IV).",
            "criterions": [
                {
                    "exact_snippets": "Histologically or cytologically proven diagnosis",
                    "criterion": "diagnosis method",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "advanced lung adenocarcinoma",
                    "criterion": "lung adenocarcinoma",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "advanced"
                        }
                    ]
                },
                {
                    "exact_snippets": "locally advanced or metastatic (stage III/IV)",
                    "criterion": "cancer stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "locally advanced",
                                "metastatic",
                                "stage III",
                                "stage IV"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Positive for translocation or inversion events involving the ALK gene locus as determined standard methods (including but not limited to by FISH and IHC testing).",
            "criterions": [
                {
                    "exact_snippets": "Positive for translocation or inversion events involving the ALK gene locus",
                    "criterion": "ALK gene locus",
                    "requirements": [
                        {
                            "requirement_type": "translocation or inversion events",
                            "expected_value": "positive"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No prior treatment with crizotinib, but they may have received prior cytotoxic chemotherapy.",
            "criterions": [
                {
                    "exact_snippets": "No prior treatment with crizotinib",
                    "criterion": "prior treatment with crizotinib",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "they may have received prior cytotoxic chemotherapy",
                    "criterion": "prior cytotoxic chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Age ≥ 18 years.",
            "criterions": [
                {
                    "exact_snippets": "Age ≥ 18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Measurable (RECIST 1.1) indicator lesion not previously irradiated.",
            "criterions": [
                {
                    "exact_snippets": "Measurable (RECIST 1.1) indicator lesion",
                    "criterion": "indicator lesion",
                    "requirements": [
                        {
                            "requirement_type": "measurability",
                            "expected_value": "RECIST 1.1"
                        }
                    ]
                },
                {
                    "exact_snippets": "indicator lesion not previously irradiated",
                    "criterion": "indicator lesion",
                    "requirements": [
                        {
                            "requirement_type": "irradiation history",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Karnofsky Performance Status ≥ 70%",
            "criterions": [
                {
                    "exact_snippets": "Karnofsky Performance Status ≥ 70%",
                    "criterion": "Karnofsky Performance Status",
                    "requirements": [
                        {
                            "requirement_type": "performance status",
                            "expected_value": {
                                "operator": ">=",
                                "value": 70,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Able to take oral medications",
            "criterions": [
                {
                    "exact_snippets": "Able to take oral medications",
                    "criterion": "ability to take oral medications",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* A negative serum pregnancy test obtained within two weeks prior to administration of the experimental agents in all pre-menopausal women (last menstrual period ≤ 24 months ago).",
            "criterions": [
                {
                    "exact_snippets": "negative serum pregnancy test",
                    "criterion": "serum pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "pre-menopausal women (last menstrual period ≤ 24 months ago)",
                    "criterion": "pre-menopausal status",
                    "requirements": [
                        {
                            "requirement_type": "last menstrual period",
                            "expected_value": {
                                "operator": "<=",
                                "value": 24,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* All women of child bearing potential (WOCBP) and sexually active men must agree to use adequate methods of birth control throughout the study which include use of oral contraceptives with an additional barrier method, double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), Depo-Provera, partner vasectomy and/or tubal libation and total abstinence.",
            "criterions": [
                {
                    "exact_snippets": "All women of child bearing potential (WOCBP)",
                    "criterion": "women of child bearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "sexually active men",
                    "criterion": "sexually active men",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must agree to use adequate methods of birth control throughout the study",
                    "criterion": "use of birth control",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "which include use of oral contraceptives with an additional barrier method, double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), Depo-Provera, partner vasectomy and/or tubal libation and total abstinence",
                    "criterion": "methods of birth control",
                    "requirements": [
                        {
                            "requirement_type": "types",
                            "expected_value": [
                                "oral contraceptives with an additional barrier method",
                                "double barrier methods",
                                "Depo-Provera",
                                "partner vasectomy",
                                "tubal libation",
                                "total abstinence"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "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": "* Prior crizotinib therapy",
            "criterions": [
                {
                    "exact_snippets": "Prior crizotinib therapy",
                    "criterion": "crizotinib therapy",
                    "requirements": [
                        {
                            "requirement_type": "prior",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Inadequate recovery from any toxicity related to prior treatment (to Grade 1 or baseline).",
            "criterions": [
                {
                    "exact_snippets": "Inadequate recovery from any toxicity related to prior treatment (to Grade 1 or baseline).",
                    "criterion": "recovery from toxicity",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "Grade 1 or baseline"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Inadequate hematologic function defined as:",
            "criterions": [
                {
                    "exact_snippets": "Inadequate hematologic function",
                    "criterion": "hematologic function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Absolute neutrophil count (ANC) < 1,000 cells/mm³.",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count (ANC) < 1,000 cells/mm³.",
                    "criterion": "absolute neutrophil count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 1000,
                                "unit": "cells/mm³"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelet count < 75,000/mm³",
            "criterions": [
                {
                    "exact_snippets": "Platelet count < 75,000/mm³",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 75000,
                                "unit": "mm³"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hemoglobin < 9.0g/dL.",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin < 9.0g/dL",
                    "criterion": "hemoglobin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 9.0,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Inadequate hepatic function defined by:",
            "criterions": [
                {
                    "exact_snippets": "Inadequate hepatic function",
                    "criterion": "hepatic function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": "inadequate"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* AST and/or ALT > 3x upper limited of normal (ULN).",
            "criterions": [
                {
                    "exact_snippets": "AST and/or ALT > 3x upper limited of normal (ULN).",
                    "criterion": "AST",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 3,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "AST and/or ALT > 3x upper limited of normal (ULN).",
                    "criterion": "ALT",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 3,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Total bilirubin > 2x ULN.",
            "criterions": [
                {
                    "exact_snippets": "Total bilirubin > 2x ULN.",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 2,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Alkaline phosphatase > 3x ULN.",
            "criterions": [
                {
                    "exact_snippets": "Alkaline phosphatase > 3x ULN",
                    "criterion": "alkaline phosphatase",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 3,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with hepatic metastases may have ALT/AST ≤ 5x ULN.",
            "criterions": [
                {
                    "exact_snippets": "hepatic metastases",
                    "criterion": "hepatic metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ALT/AST ≤ 5x ULN",
                    "criterion": "ALT/AST levels",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with hepatic and/or bone metastases may have an AP ≤ 5x ULN.",
            "criterions": [
                {
                    "exact_snippets": "hepatic and/or bone metastases",
                    "criterion": "metastases",
                    "requirements": [
                        {
                            "requirement_type": "location",
                            "expected_value": [
                                "hepatic",
                                "bone"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "AP ≤ 5x ULN",
                    "criterion": "alkaline phosphatase (AP)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Inadequate renal function defined by serum creatinine > 2x ULN Uncontrolled systemic fungal, bacterial, viral or other infection (defined as exhibiting ongoing signs/symptoms related to infection without improvement, despite appropriate anti-infective medications or other treatment).",
            "criterions": [
                {
                    "exact_snippets": "Inadequate renal function defined by serum creatinine > 2x ULN",
                    "criterion": "renal function",
                    "requirements": [
                        {
                            "requirement_type": "serum creatinine level",
                            "expected_value": {
                                "operator": ">",
                                "value": 2,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled systemic fungal, bacterial, viral or other infection (defined as exhibiting ongoing signs/symptoms related to infection without improvement, despite appropriate anti-infective medications or other treatment)",
                    "criterion": "systemic infection",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "uncontrolled"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with clinically active brain metastasis (requiring therapy with steroids or radiation therapy). Patients with clinically stable brain metastases (previously treated or untreated) for two weeks are eligible.",
            "criterions": [
                {
                    "exact_snippets": "clinically active brain metastasis (requiring therapy with steroids or radiation therapy)",
                    "criterion": "clinically active brain metastasis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "clinically stable brain metastases (previously treated or untreated) for two weeks",
                    "criterion": "clinically stable brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Significant cardiac disease (e.g. New York Heart Association (NYHA) Class 3 or 4; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty or coronary artery bypass graft (CABG) within the past 6 months; or uncontrolled atrial or ventricular cardiac arrhythmias).",
            "criterions": [
                {
                    "exact_snippets": "Significant cardiac disease (e.g. New York Heart Association (NYHA) Class 3 or 4",
                    "criterion": "cardiac disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "NYHA Class 3",
                                "NYHA Class 4"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "myocardial infarction within the past 6 months",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "unstable angina",
                    "criterion": "angina",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": "unstable"
                        }
                    ]
                },
                {
                    "exact_snippets": "coronary angioplasty or coronary artery bypass graft (CABG) within the past 6 months",
                    "criterion": "coronary angioplasty or coronary artery bypass graft (CABG)",
                    "requirements": [
                        {
                            "requirement_type": "time since procedure",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled atrial or ventricular cardiac arrhythmias",
                    "criterion": "atrial or ventricular cardiac arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Previously or current malignancies at other sites within the last 2 years, with the exception of adequately treated in situ carcinoma of the cervix, basal or squamous cell carcinoma of the skin, or prostate cancer that does not require active treatment per National Comprehensive Cancer Network (NCCN) guidelines.",
            "criterions": [
                {
                    "exact_snippets": "Previously or current malignancies at other sites within the last 2 years",
                    "criterion": "malignancies at other sites",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "adequately treated in situ carcinoma of the cervix",
                    "criterion": "in situ carcinoma of the cervix",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "adequately treated"
                        }
                    ]
                },
                {
                    "exact_snippets": "basal or squamous cell carcinoma of the skin",
                    "criterion": "basal or squamous cell carcinoma of the skin",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "adequately treated"
                        }
                    ]
                },
                {
                    "exact_snippets": "prostate cancer that does not require active treatment per National Comprehensive Cancer Network (NCCN) guidelines",
                    "criterion": "prostate cancer",
                    "requirements": [
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": "does not require active treatment per National Comprehensive Cancer Network (NCCN) guidelines"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women who are pregnant or lactating",
            "criterions": [
                {
                    "exact_snippets": "Women who are pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "lactating",
                    "criterion": "lactation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Use of drugs or food that are known potent CYP3A4 inhibitors (see Appendix C)",
            "criterions": [
                {
                    "exact_snippets": "Use of drugs or food that are known potent CYP3A4 inhibitors",
                    "criterion": "use of CYP3A4 inhibitors",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Use of drugs that are known potent CYP3A4 inducers (see Appendix D)",
            "criterions": [
                {
                    "exact_snippets": "Use of drugs that are known potent CYP3A4 inducers",
                    "criterion": "use of CYP3A4 inducers",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any other condition that, in the opinion of the Investigator, may compromise the safety, compliance of the patient, or would preclude the patient from successful completion of the study.",
            "criterions": [
                {
                    "exact_snippets": "Any other condition ... may compromise the safety",
                    "criterion": "condition compromising safety",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Any other condition ... compliance of the patient",
                    "criterion": "condition affecting compliance",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Any other condition ... preclude the patient from successful completion of the study",
                    "criterion": "condition precluding study completion",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}