{
    "info": {
        "nct_id": "NCT01016860",
        "official_title": "A Phase I/IB Study of OSI-906 and Irinotecan in Patients With Advanced Cancer With Expanded Cohorts of Patients With Colorectal Cancer Stratified by the OSI-906 Integrated Classifier",
        "inclusion_criteria": "• Dose Escalation Phase: Histological or cytopathological diagnosis of an advanced cancer that is refractory to standard therapy or for which no standard therapy exists.\n\nIrinotecan must be listed in the Compendia for reimbursement, ie. colorectal cancer; lung cancer; gastric; esophageal, cervical and ovarian cancer.\n\n* Cohort Expansion Phase: Histological or cytopathological diagnosis of advanced colorectal cancer with known Kirsten rat sarcoma (KRAS) mutation status. All patients must have received and progressed or be intolerable of first-line therapy with an oxaliplatin-containing regimen. Patients must be screened using the OSI-906 integrated classifier.\n* Cohort 1 (12 patients): Window of opportunity cohort: Patients with a score of at least 4 out of 5 by the OSI-906 integrated classifier who are irinotecan-naive will receive OSI-906 as a single agent until disease progression. Patients must be non surgically resectable or not a surgical candidate because of comorbid conditions. At disease progression, if the patient had a best response of at least stable disease for 3 cycles (9 weeks), irinotecan may be added to OSI-906.\n* Cohort 2: (16 patients: 8 KRAS wild-type (WT) and 8 KRAS Mutant(MT). Patients who have score of less than 4 by the OSI-906 integrated classifier will have OSI-906 added to irinotecan on disease progression to irinotecan (patients that are KRAS WT will have received cetuximab with irinotecan). Patients who are treated in the dose escalation phase at the recommended phase II dose of the combination and meet the criteria for Cohort 2 of the expanded phase may be counted towards the dose expansion patient numbers.\n* Age ≥18 years old\n* Patients must have an Eastern Co-operative oncology group (ECOG) performance status of 0-1\n* Life expectancy of at least three months.\n* Adequate hematological function and bone marrow reserve:\n\nHematopoetic: Neutrophil count ≥ 1.5 x 109/L (1,500/mm3), Platelet count ≥ 75 x 109/L, Hemoglobin ≥ 9.0g/dL\n\n* Adequate hepatic and renal function Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 fold upper limit of normal (ULN) Bilirubin ≤ 1.5 X ULN Creatinine ≤ 1.5 fold ULN or calculated creatinine clearance, using the Cockcroft-Gault formula > 60 mL/min, if just below 60 mL/min then Glomerular Filtration Rate > 60 mL/min as determined by 24 hour urine collection\n* Measurable (according to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria in the dose expansion cohorts or measurable /evaluable disease in the Dose Escalation phase,\n* Ability to understand the requirements of the study, provide written informed consent and comply with the study protocol procedures.\n\nA: Documentation of KRAS status must be performed prior to enrollment.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Concurrent symptomatic central nervous system involvement, brain or meningeal metastases\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, uncontrolled diabetes, uncontrollable hypertension or psychiatric illness/social situations that would limit compliance with study requirements\n* Documented history of diabetes\n* Corrected QT (QTc) interval > 450 msec at baseline\n* Drugs with a Risk of Causing corrected QT interval Prolongation: Drugs that have a risk of causing QT interval prolongation are prohibited within 14 days prior to Day 1 dosing and while on study to avoid exacerbation of any OSI-906 potential side effects\n* Known positive serology for the human immunodeficiency virus (HIV), Hepatitis B and/or Hepatitis C\n* Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption\n* Gastrointestinal tract disease (including peptic ulcer disease) or prior surgery resulting in an inability to take oral medications\n* Patients may have had prior therapy, providing the following conditions are met:\n\nChemotherapy: A minimum of 3 weeks (4 weeks for carboplatin or investigational anticancer agents and 6 weeks for nitrosoureas and mitomycin C) must have elapsed between the end of treatment and start of treatment. Patients must have recovered from any treatment-related toxicities (except for alopecia, fatigue, and grade 1 neurotoxicity) prior to start of treatment.\n\nHormonal therapy: Patients may have had prior anticancer hormonal therapy provided it is discontinued prior to start of treatment. However, patients with prostate cancer with evidence of progressive disease may continue on therapy that produces medical castration (eg, goserelin or leuprorelin), provided this therapy was commenced at least 3 months earlier.\n\nRadiation: Patients may have had prior radiation therapy provided they have recovered from the acute, toxic effects of radiotherapy prior to start of treatment. A minimum of 21 days must have elapsed between the end of radiotherapy and start of treatment if the radiation affected more than 25% of bone marrow otherwise a 14 days wash out is required.\n\nSurgery: Previous surgery is permitted provided that wound healing has occurred prior to start of treatment.\n\n• Laboratory results: international normalized ratio (INR) ≥ 1.5 X ULN and activated partial thromboplastin time (aPTT) ≥ 1.5 X ULN\n\nFasting blood glucose of >125mg/dL at baseline and on Day 1 of dosing.\n\n* Women who are pregnant or breast feeding because of teratogenic potential.\n* Women of childbearing potential in whom pregnancy cannot be excluded or who are not using an adequate method of contraception because of teratogenic potential.\n* Prior documented hypersensitivity to irinotecan",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "• Dose Escalation Phase: Histological or cytopathological diagnosis of an advanced cancer that is refractory to standard therapy or for which no standard therapy exists.",
            "criterions": [
                {
                    "exact_snippets": "Histological or cytopathological diagnosis of an advanced cancer",
                    "criterion": "advanced cancer diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "histological",
                                "cytopathological"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "refractory to standard therapy",
                    "criterion": "cancer refractory to standard therapy",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "for which no standard therapy exists",
                    "criterion": "cancer with no standard therapy",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "Irinotecan must be listed in the Compendia for reimbursement, ie. colorectal cancer; lung cancer; gastric; esophageal, cervical and ovarian cancer.",
            "criterions": [
                {
                    "exact_snippets": "Irinotecan must be listed in the Compendia for reimbursement",
                    "criterion": "irinotecan listing in Compendia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "colorectal cancer",
                    "criterion": "colorectal cancer",
                    "requirements": [
                        {
                            "requirement_type": "indication",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "lung cancer",
                    "criterion": "lung cancer",
                    "requirements": [
                        {
                            "requirement_type": "indication",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "gastric",
                    "criterion": "gastric cancer",
                    "requirements": [
                        {
                            "requirement_type": "indication",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "esophageal",
                    "criterion": "esophageal cancer",
                    "requirements": [
                        {
                            "requirement_type": "indication",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "cervical",
                    "criterion": "cervical cancer",
                    "requirements": [
                        {
                            "requirement_type": "indication",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ovarian cancer",
                    "criterion": "ovarian cancer",
                    "requirements": [
                        {
                            "requirement_type": "indication",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Cohort Expansion Phase: Histological or cytopathological diagnosis of advanced colorectal cancer with known Kirsten rat sarcoma (KRAS) mutation status. All patients must have received and progressed or be intolerable of first-line therapy with an oxaliplatin-containing regimen. Patients must be screened using the OSI-906 integrated classifier.",
            "criterions": [
                {
                    "exact_snippets": "Histological or cytopathological diagnosis of advanced colorectal cancer",
                    "criterion": "advanced colorectal cancer",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis",
                            "expected_value": "histological or cytopathological"
                        }
                    ]
                },
                {
                    "exact_snippets": "known Kirsten rat sarcoma (KRAS) mutation status",
                    "criterion": "KRAS mutation status",
                    "requirements": [
                        {
                            "requirement_type": "known",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "received and progressed or be intolerable of first-line therapy with an oxaliplatin-containing regimen",
                    "criterion": "first-line therapy with an oxaliplatin-containing regimen",
                    "requirements": [
                        {
                            "requirement_type": "treatment history",
                            "expected_value": "received and progressed or be intolerable"
                        }
                    ]
                },
                {
                    "exact_snippets": "screened using the OSI-906 integrated classifier",
                    "criterion": "OSI-906 integrated classifier",
                    "requirements": [
                        {
                            "requirement_type": "screening",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Cohort 1 (12 patients): Window of opportunity cohort: Patients with a score of at least 4 out of 5 by the OSI-906 integrated classifier who are irinotecan-naive will receive OSI-906 as a single agent until disease progression. Patients must be non surgically resectable or not a surgical candidate because of comorbid conditions. At disease progression, if the patient had a best response of at least stable disease for 3 cycles (9 weeks), irinotecan may be added to OSI-906.",
            "criterions": [
                {
                    "exact_snippets": "score of at least 4 out of 5 by the OSI-906 integrated classifier",
                    "criterion": "OSI-906 integrated classifier score",
                    "requirements": [
                        {
                            "requirement_type": "minimum score",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "out of 5"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "irinotecan-naive",
                    "criterion": "irinotecan exposure",
                    "requirements": [
                        {
                            "requirement_type": "exposure",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "non surgically resectable or not a surgical candidate because of comorbid conditions",
                    "criterion": "surgical resectability",
                    "requirements": [
                        {
                            "requirement_type": "resectability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "non surgically resectable or not a surgical candidate because of comorbid conditions",
                    "criterion": "surgical candidacy",
                    "requirements": [
                        {
                            "requirement_type": "candidacy",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Cohort 2: (16 patients: 8 KRAS wild-type (WT) and 8 KRAS Mutant(MT). Patients who have score of less than 4 by the OSI-906 integrated classifier will have OSI-906 added to irinotecan on disease progression to irinotecan (patients that are KRAS WT will have received cetuximab with irinotecan). Patients who are treated in the dose escalation phase at the recommended phase II dose of the combination and meet the criteria for Cohort 2 of the expanded phase may be counted towards the dose expansion patient numbers.",
            "criterions": [
                {
                    "exact_snippets": "8 KRAS wild-type (WT)",
                    "criterion": "KRAS status",
                    "requirements": [
                        {
                            "requirement_type": "mutation",
                            "expected_value": "wild-type"
                        }
                    ]
                },
                {
                    "exact_snippets": "8 KRAS Mutant(MT)",
                    "criterion": "KRAS status",
                    "requirements": [
                        {
                            "requirement_type": "mutation",
                            "expected_value": "mutant"
                        }
                    ]
                },
                {
                    "exact_snippets": "score of less than 4 by the OSI-906 integrated classifier",
                    "criterion": "OSI-906 integrated classifier score",
                    "requirements": [
                        {
                            "requirement_type": "score",
                            "expected_value": {
                                "operator": "<",
                                "value": 4,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "treated in the dose escalation phase at the recommended phase II dose of the combination",
                    "criterion": "treatment phase",
                    "requirements": [
                        {
                            "requirement_type": "phase",
                            "expected_value": "dose escalation phase at the recommended phase II dose"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Age ≥18 years old",
            "criterions": [
                {
                    "exact_snippets": "Age ≥18 years old",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have an Eastern Co-operative oncology group (ECOG) performance status of 0-1",
            "criterions": [
                {
                    "exact_snippets": "Eastern Co-operative oncology group (ECOG) performance status of 0-1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 1,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Life expectancy of at least three months.",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy of at least three months.",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Hematopoetic: Neutrophil count ≥ 1.5 x 109/L (1,500/mm3), Platelet count ≥ 75 x 109/L, Hemoglobin ≥ 9.0g/dL",
            "criterions": [
                {
                    "exact_snippets": "Neutrophil count ≥ 1.5 x 109/L (1,500/mm3)",
                    "criterion": "neutrophil count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "x 10^9/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Platelet count ≥ 75 x 109/L",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 75,
                                "unit": "x 10^9/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Hemoglobin ≥ 9.0g/dL",
                    "criterion": "hemoglobin",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9.0,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate hepatic and renal function Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 fold upper limit of normal (ULN) Bilirubin ≤ 1.5 X ULN Creatinine ≤ 1.5 fold ULN or calculated creatinine clearance, using the Cockcroft-Gault formula > 60 mL/min, if just below 60 mL/min then Glomerular Filtration Rate > 60 mL/min as determined by 24 hour urine collection",
            "criterions": [
                {
                    "exact_snippets": "Adequate hepatic and renal function",
                    "criterion": "hepatic and renal function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Aspartate transaminase (AST) ... ≤ 2.5 fold upper limit of normal (ULN)",
                    "criterion": "Aspartate transaminase (AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "fold ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alanine transaminase (ALT) ≤ 2.5 fold upper limit of normal (ULN)",
                    "criterion": "alanine transaminase (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "fold ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Bilirubin ≤ 1.5 X ULN",
                    "criterion": "Bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "X ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Creatinine ≤ 1.5 fold ULN",
                    "criterion": "Creatinine",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "fold ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "calculated creatinine clearance, using the Cockcroft-Gault formula > 60 mL/min",
                    "criterion": "calculated creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 60,
                                "unit": "mL/min"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Glomerular Filtration Rate > 60 mL/min as determined by 24 hour urine collection",
                    "criterion": "Glomerular Filtration Rate",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 60,
                                "unit": "mL/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Measurable (according to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria in the dose expansion cohorts or measurable /evaluable disease in the Dose Escalation phase,",
            "criterions": [
                {
                    "exact_snippets": "Measurable (according to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria",
                    "criterion": "measurable disease",
                    "requirements": [
                        {
                            "requirement_type": "evaluation criteria",
                            "expected_value": "Response Evaluation Criteria in Solid Tumors (RECIST)"
                        }
                    ]
                },
                {
                    "exact_snippets": "measurable /evaluable disease in the Dose Escalation phase",
                    "criterion": "measurable/evaluable disease",
                    "requirements": [
                        {
                            "requirement_type": "phase",
                            "expected_value": "Dose Escalation"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Ability to understand the requirements of the study, provide written informed consent and comply with the study protocol procedures.",
            "criterions": [
                {
                    "exact_snippets": "Ability to understand the requirements of the study",
                    "criterion": "understanding of study requirements",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "provide written informed consent",
                    "criterion": "written informed consent",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "comply with the study protocol procedures",
                    "criterion": "compliance with study protocol",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "A: Documentation of KRAS status must be performed prior to enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Documentation of KRAS status must be performed",
                    "criterion": "KRAS status",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "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": "* Concurrent symptomatic central nervous system involvement, brain or meningeal metastases",
            "criterions": [
                {
                    "exact_snippets": "Concurrent symptomatic central nervous system involvement",
                    "criterion": "central nervous system involvement",
                    "requirements": [
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "concurrent",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "brain ... metastases",
                    "criterion": "brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "meningeal metastases",
                    "criterion": "meningeal metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, uncontrolled diabetes, uncontrollable hypertension or psychiatric illness/social situations that would limit compliance with study requirements",
            "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": "unstable cardiac arrhythmia",
                    "criterion": "cardiac arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": "unstable"
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled diabetes",
                    "criterion": "diabetes",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "uncontrolled"
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrollable hypertension",
                    "criterion": "hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "uncontrollable"
                        }
                    ]
                },
                {
                    "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": "would limit compliance with study requirements"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Documented history of diabetes",
            "criterions": [
                {
                    "exact_snippets": "Documented history of diabetes",
                    "criterion": "diabetes",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Corrected QT (QTc) interval > 450 msec at baseline",
            "criterions": [
                {
                    "exact_snippets": "Corrected QT (QTc) interval > 450 msec",
                    "criterion": "Corrected QT (QTc) interval",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 450,
                                "unit": "msec"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Drugs with a Risk of Causing corrected QT interval Prolongation: Drugs that have a risk of causing QT interval prolongation are prohibited within 14 days prior to Day 1 dosing and while on study to avoid exacerbation of any OSI-906 potential side effects",
            "criterions": [
                {
                    "exact_snippets": "Drugs with a Risk of Causing corrected QT interval Prolongation",
                    "criterion": "drugs with a risk of causing QT interval prolongation",
                    "requirements": [
                        {
                            "requirement_type": "prohibition period",
                            "expected_value": "within 14 days prior to Day 1 dosing and while on study"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known positive serology for the human immunodeficiency virus (HIV), Hepatitis B and/or Hepatitis C",
            "criterions": [
                {
                    "exact_snippets": "Known positive serology for the human immunodeficiency virus (HIV)",
                    "criterion": "HIV serology",
                    "requirements": [
                        {
                            "requirement_type": "serology",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "Known positive serology for ... Hepatitis B",
                    "criterion": "Hepatitis B serology",
                    "requirements": [
                        {
                            "requirement_type": "serology",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "Known positive serology for ... Hepatitis C",
                    "criterion": "Hepatitis C serology",
                    "requirements": [
                        {
                            "requirement_type": "serology",
                            "expected_value": "positive"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption",
            "criterions": [
                {
                    "exact_snippets": "Refractory nausea and vomiting",
                    "criterion": "nausea and vomiting",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "refractory"
                        }
                    ]
                },
                {
                    "exact_snippets": "chronic gastrointestinal diseases (e.g. inflammatory bowel disease)",
                    "criterion": "gastrointestinal diseases",
                    "requirements": [
                        {
                            "requirement_type": "chronicity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "significant bowel resection that would preclude adequate absorption",
                    "criterion": "bowel resection",
                    "requirements": [
                        {
                            "requirement_type": "impact on absorption",
                            "expected_value": "preclude adequate absorption"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Gastrointestinal tract disease (including peptic ulcer disease) or prior surgery resulting in an inability to take oral medications",
            "criterions": [
                {
                    "exact_snippets": "Gastrointestinal tract disease (including peptic ulcer disease)",
                    "criterion": "gastrointestinal tract disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "prior surgery resulting in an inability to take oral medications",
                    "criterion": "prior surgery",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "inability to take oral medications"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients may have had prior therapy, providing the following conditions are met:",
            "criterions": [
                {
                    "exact_snippets": "Patients may have had prior therapy",
                    "criterion": "prior therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Chemotherapy: A minimum of 3 weeks (4 weeks for carboplatin or investigational anticancer agents and 6 weeks for nitrosoureas and mitomycin C) must have elapsed between the end of treatment and start of treatment. Patients must have recovered from any treatment-related toxicities (except for alopecia, fatigue, and grade 1 neurotoxicity) prior to start of treatment.",
            "criterions": [
                {
                    "exact_snippets": "Chemotherapy: A minimum of 3 weeks ... must have elapsed between the end of treatment and start of treatment.",
                    "criterion": "elapsed time since chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "minimum duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "4 weeks for carboplatin or investigational anticancer agents",
                    "criterion": "elapsed time since carboplatin or investigational anticancer agents",
                    "requirements": [
                        {
                            "requirement_type": "minimum duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "6 weeks for nitrosoureas and mitomycin C",
                    "criterion": "elapsed time since nitrosoureas and mitomycin C",
                    "requirements": [
                        {
                            "requirement_type": "minimum duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients must have recovered from any treatment-related toxicities",
                    "criterion": "recovery from treatment-related toxicities",
                    "requirements": [
                        {
                            "requirement_type": "recovery",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "except for alopecia, fatigue, and grade 1 neurotoxicity",
                    "criterion": "treatment-related toxicities exceptions",
                    "requirements": [
                        {
                            "requirement_type": "exceptions",
                            "expected_value": [
                                "alopecia",
                                "fatigue",
                                "grade 1 neurotoxicity"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "Hormonal therapy: Patients may have had prior anticancer hormonal therapy provided it is discontinued prior to start of treatment. However, patients with prostate cancer with evidence of progressive disease may continue on therapy that produces medical castration (eg, goserelin or leuprorelin), provided this therapy was commenced at least 3 months earlier.",
            "criterions": [
                {
                    "exact_snippets": "Patients may have had prior anticancer hormonal therapy provided it is discontinued prior to start of treatment.",
                    "criterion": "prior anticancer hormonal therapy",
                    "requirements": [
                        {
                            "requirement_type": "discontinuation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "patients with prostate cancer with evidence of progressive disease may continue on therapy that produces medical castration ... provided this therapy was commenced at least 3 months earlier.",
                    "criterion": "therapy that produces medical castration",
                    "requirements": [
                        {
                            "requirement_type": "continuation",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "commencement time",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Radiation: Patients may have had prior radiation therapy provided they have recovered from the acute, toxic effects of radiotherapy prior to start of treatment. A minimum of 21 days must have elapsed between the end of radiotherapy and start of treatment if the radiation affected more than 25% of bone marrow otherwise a 14 days wash out is required.",
            "criterions": [
                {
                    "exact_snippets": "prior radiation therapy",
                    "criterion": "prior radiation therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "recovered from the acute, toxic effects of radiotherapy",
                    "criterion": "recovery from acute, toxic effects of radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "recovery",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "A minimum of 21 days must have elapsed between the end of radiotherapy and start of treatment if the radiation affected more than 25% of bone marrow",
                    "criterion": "elapsed time since radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time elapsed",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 21,
                                        "unit": "days"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "bone marrow affected",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">",
                                        "value": 25,
                                        "unit": "%"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "a 14 days wash out is required",
                    "criterion": "wash out period",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "=",
                                        "value": 14,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Surgery: Previous surgery is permitted provided that wound healing has occurred prior to start of treatment.",
            "criterions": [
                {
                    "exact_snippets": "Previous surgery is permitted",
                    "criterion": "previous surgery",
                    "requirements": [
                        {
                            "requirement_type": "permitted",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "wound healing has occurred prior to start of treatment",
                    "criterion": "wound healing",
                    "requirements": [
                        {
                            "requirement_type": "occurrence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "• Laboratory results: international normalized ratio (INR) ≥ 1.5 X ULN and activated partial thromboplastin time (aPTT) ≥ 1.5 X ULN",
            "criterions": [
                {
                    "exact_snippets": "international normalized ratio (INR) ≥ 1.5 X ULN",
                    "criterion": "international normalized ratio (INR)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "X ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "activated partial thromboplastin time (aPTT) ≥ 1.5 X ULN",
                    "criterion": "activated partial thromboplastin time (aPTT)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "X ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Fasting blood glucose of >125mg/dL at baseline and on Day 1 of dosing.",
            "criterions": [
                {
                    "exact_snippets": "Fasting blood glucose of >125mg/dL at baseline",
                    "criterion": "fasting blood glucose",
                    "requirements": [
                        {
                            "requirement_type": "measurement",
                            "expected_value": {
                                "operator": ">",
                                "value": 125,
                                "unit": "mg/dL"
                            }
                        },
                        {
                            "requirement_type": "timing",
                            "expected_value": "baseline"
                        }
                    ]
                },
                {
                    "exact_snippets": "Fasting blood glucose of >125mg/dL ... on Day 1 of dosing",
                    "criterion": "fasting blood glucose",
                    "requirements": [
                        {
                            "requirement_type": "measurement",
                            "expected_value": {
                                "operator": ">",
                                "value": 125,
                                "unit": "mg/dL"
                            }
                        },
                        {
                            "requirement_type": "timing",
                            "expected_value": "Day 1 of dosing"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women who are pregnant or breast feeding because of teratogenic potential.",
            "criterions": [
                {
                    "exact_snippets": "Women who are pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "breast feeding",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women of childbearing potential in whom pregnancy cannot be excluded or who are not using an adequate method of contraception because of teratogenic potential.",
            "criterions": [
                {
                    "exact_snippets": "Women of childbearing potential",
                    "criterion": "childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "pregnancy cannot be excluded",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "not using an adequate method of contraception",
                    "criterion": "contraception method",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "teratogenic potential",
                    "criterion": "teratogenic potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior documented hypersensitivity to irinotecan",
            "criterions": [
                {
                    "exact_snippets": "Prior documented hypersensitivity to irinotecan",
                    "criterion": "hypersensitivity to irinotecan",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "* Adequate hematological function and bone marrow reserve:",
            "criterions": [
                {
                    "exact_snippets": "Adequate hematological function",
                    "criterion": "hematological function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "adequate ... bone marrow reserve",
                    "criterion": "bone marrow reserve",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}