{
    "info": {
        "nct_id": "NCT01802320",
        "official_title": "A Phase 2 Study of MK-2206 in Previously Treated Metastatic Colorectal Cancer Patients Enriched for PTEN Loss and PIK3CA Mutation",
        "inclusion_criteria": "* Patients must have histologically confirmed, radiologically measurable metastatic or locally advanced unresectable colorectal adenocarcinoma that is amenable to image-guided biopsy; disease in previously radiated regions may not be considered measurable unless there has been demonstrated progression in the lesion\n* Patients must have progressed on or been intolerant to a fluoropyrimidine-based chemotherapy regimen; there is no limit on the number of prior treatment regimens permitted\n* Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)\n* Life expectancy of greater than 12 weeks\n* Leukocytes >= 3,000/mcL\n* Absolute neutrophil count >= 1,500/mcL\n* Platelets >= 100,000/mcL\n* Total bilirubin =< institution upper limit of normal\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 X institutional upper limit of normal or =< 5 X institutional upper limit of normal for patients with known liver metastasis\n* Creatinine =< institution upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal\n* Women of child-bearing potential and men must agree to use adequate contraception (double barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 4 months after completion of MK-2206 administration; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of MK-2206 administration\n* Patients must be able to swallow whole tablets; nasogastric or gastrostomy (G) tube administration is not allowed; tablets must not be crushed or chewed\n* Ability to understand and the willingness to sign a written informed consent document\n* Tumor must be wild type for the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and BRAF oncogenes, and must have known PIK3CA, AKT mutation status and PTEN expression status\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study; if the patient has residual toxicity from prior treatment, toxicity must be =< grade 1 (or =< grade 2 for peripheral neuropathy and/or alopecia)\n* Patients who are receiving or have received any other investigational agents within 30 days of study day 1, or who have previously received MK-2206 at any time\n* Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; however, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 1 month prior to entry as defined as:\n\n  * No evidence of new or enlarging CNS metastasis\n  * Off steroids that are used to minimize surrounding brain edema\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206\n* Patients receiving any medications or substances that are inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP450 3A4) are ineligible\n* Patients with diabetes or in risk for hyperglycemia should not be excluded from trials with MK-2206, but the hyperglycemia should be well controlled on oral agents before the patient enters the trial\n* Cardiovascular baseline corrected QT by Fridericia's (QTcF) > 450 msec (male) or QTcF > 470 msec (female) will exclude patients from entry on study\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements\n* Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with MK-2206\n* Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible\n* No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Patients must have histologically confirmed, radiologically measurable metastatic or locally advanced unresectable colorectal adenocarcinoma that is amenable to image-guided biopsy; disease in previously radiated regions may not be considered measurable unless there has been demonstrated progression in the lesion",
            "criterions": [
                {
                    "exact_snippets": "histologically confirmed",
                    "criterion": "colorectal adenocarcinoma",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": "histologically confirmed"
                        }
                    ]
                },
                {
                    "exact_snippets": "radiologically measurable",
                    "criterion": "colorectal adenocarcinoma",
                    "requirements": [
                        {
                            "requirement_type": "measurability",
                            "expected_value": "radiologically measurable"
                        }
                    ]
                },
                {
                    "exact_snippets": "metastatic or locally advanced unresectable",
                    "criterion": "colorectal adenocarcinoma",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "metastatic",
                                "locally advanced unresectable"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "amenable to image-guided biopsy",
                    "criterion": "colorectal adenocarcinoma",
                    "requirements": [
                        {
                            "requirement_type": "biopsy suitability",
                            "expected_value": "amenable to image-guided biopsy"
                        }
                    ]
                },
                {
                    "exact_snippets": "disease in previously radiated regions may not be considered measurable unless there has been demonstrated progression in the lesion",
                    "criterion": "disease in previously radiated regions",
                    "requirements": [
                        {
                            "requirement_type": "measurability",
                            "expected_value": "demonstrated progression in the lesion"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have progressed on or been intolerant to a fluoropyrimidine-based chemotherapy regimen; there is no limit on the number of prior treatment regimens permitted",
            "criterions": [
                {
                    "exact_snippets": "Patients must have progressed on ... a fluoropyrimidine-based chemotherapy regimen",
                    "criterion": "progression on fluoropyrimidine-based chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "progression",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients must have ... been intolerant to a fluoropyrimidine-based chemotherapy regimen",
                    "criterion": "intolerance to fluoropyrimidine-based chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "intolerance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status =< 1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Karnofsky >= 70%",
                    "criterion": "Karnofsky performance status",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 70,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Life expectancy of greater than 12 weeks",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy of greater than 12 weeks",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Leukocytes >= 3,000/mcL",
            "criterions": [
                {
                    "exact_snippets": "Leukocytes >= 3,000/mcL",
                    "criterion": "leukocytes",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3000,
                                "unit": "mcL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Absolute neutrophil count >= 1,500/mcL",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count >= 1,500/mcL",
                    "criterion": "absolute neutrophil count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1500,
                                "unit": "mcL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelets >= 100,000/mcL",
            "criterions": [
                {
                    "exact_snippets": "Platelets >= 100,000/mcL",
                    "criterion": "platelets",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100000,
                                "unit": "mcL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Total bilirubin =< institution upper limit of normal",
            "criterions": [
                {
                    "exact_snippets": "Total bilirubin =< institution upper limit of normal",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "institution upper limit of normal"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Creatinine =< institution upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal",
            "criterions": [
                {
                    "exact_snippets": "Creatinine =< institution upper limit of normal",
                    "criterion": "creatinine level",
                    "requirements": [
                        {
                            "requirement_type": "comparison",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "institution upper limit of normal"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "creatinine clearance >= 60 mL/min/1.73 m^2",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "comparison",
                            "expected_value": {
                                "operator": ">=",
                                "value": 60,
                                "unit": "mL/min/1.73 m^2"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women of child-bearing potential and men must agree to use adequate contraception (double barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 4 months after completion of MK-2206 administration; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of MK-2206 administration",
            "criterions": [
                {
                    "exact_snippets": "Women of child-bearing potential",
                    "criterion": "women of child-bearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must agree to use adequate contraception (double barrier method of birth control; abstinence)",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "double barrier method of birth control",
                                "abstinence"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "men must agree to use adequate contraception",
                    "criterion": "contraception use for men",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must be able to swallow whole tablets; nasogastric or gastrostomy (G) tube administration is not allowed; tablets must not be crushed or chewed",
            "criterions": [
                {
                    "exact_snippets": "Patients must be able to swallow whole tablets",
                    "criterion": "ability to swallow whole tablets",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "nasogastric or gastrostomy (G) tube administration is not allowed",
                    "criterion": "nasogastric or gastrostomy tube administration",
                    "requirements": [
                        {
                            "requirement_type": "allowance",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "tablets must not be crushed or chewed",
                    "criterion": "crushing or chewing tablets",
                    "requirements": [
                        {
                            "requirement_type": "allowance",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Ability to understand and the willingness to sign a written informed consent document",
            "criterions": [
                {
                    "exact_snippets": "Ability to understand",
                    "criterion": "cognitive ability",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "willingness to sign a written informed consent document",
                    "criterion": "willingness to consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "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": "* Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; however, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 1 month prior to entry as defined as:",
            "criterions": [
                {
                    "exact_snippets": "known active central nervous system (CNS) metastases",
                    "criterion": "active CNS metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "carcinomatous meningitis",
                    "criterion": "carcinomatous meningitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "CNS metastases who have completed a course of therapy",
                    "criterion": "CNS metastases therapy completion",
                    "requirements": [
                        {
                            "requirement_type": "completion",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "clinically stable for at least 1 month prior to entry",
                    "criterion": "clinical stability",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "month"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No evidence of new or enlarging CNS metastasis",
            "criterions": [
                {
                    "exact_snippets": "No evidence of new ... CNS metastasis",
                    "criterion": "CNS metastasis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "No evidence of ... enlarging CNS metastasis",
                    "criterion": "enlarging CNS metastasis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Off steroids that are used to minimize surrounding brain edema",
            "criterions": [
                {
                    "exact_snippets": "Off steroids that are used to minimize surrounding brain edema",
                    "criterion": "steroid use",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206",
            "criterions": [
                {
                    "exact_snippets": "History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206",
                    "criterion": "allergic reactions to compounds similar to MK-2206",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients receiving any medications or substances that are inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP450 3A4) are ineligible",
            "criterions": [
                {
                    "exact_snippets": "Patients receiving any medications or substances that are inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP450 3A4)",
                    "criterion": "medications or substances affecting CYP450 3A4",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with diabetes or in risk for hyperglycemia should not be excluded from trials with MK-2206, but the hyperglycemia should be well controlled on oral agents before the patient enters the trial",
            "criterions": [
                {
                    "exact_snippets": "Patients with diabetes",
                    "criterion": "diabetes",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "risk for hyperglycemia",
                    "criterion": "risk for hyperglycemia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "hyperglycemia should be well controlled on oral agents",
                    "criterion": "hyperglycemia control",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "well controlled on oral agents"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Cardiovascular baseline corrected QT by Fridericia's (QTcF) > 450 msec (male) or QTcF > 470 msec (female) will exclude patients from entry on study",
            "criterions": [
                {
                    "exact_snippets": "Cardiovascular baseline corrected QT by Fridericia's (QTcF) > 450 msec (male)",
                    "criterion": "QTcF (male)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 450,
                                "unit": "msec"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "QTcF > 470 msec (female)",
                    "criterion": "QTcF (female)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 470,
                                "unit": "msec"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, 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": "cardiac arrhythmia",
                    "criterion": "cardiac arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "psychiatric illness/social situations that would limit compliance with study requirements",
                    "criterion": "psychiatric illness/social situations",
                    "requirements": [
                        {
                            "requirement_type": "impact on compliance",
                            "expected_value": "limit"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with MK-2206",
            "criterions": [
                {
                    "exact_snippets": "Pregnant women are excluded",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "breastfeeding should be discontinued",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "discontinued"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible",
            "criterions": [
                {
                    "exact_snippets": "Human immunodeficiency virus (HIV)-positive",
                    "criterion": "HIV status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "on combination antiretroviral therapy",
                    "criterion": "combination antiretroviral therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years",
            "criterions": [
                {
                    "exact_snippets": "No other prior malignancy is allowed",
                    "criterion": "prior malignancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "adequately treated basal cell or squamous cell skin cancer",
                    "criterion": "basal cell or squamous cell skin cancer",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "adequately treated"
                        }
                    ]
                },
                {
                    "exact_snippets": "in situ cervical cancer",
                    "criterion": "cervical cancer",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "in situ"
                        }
                    ]
                },
                {
                    "exact_snippets": "adequately treated stage I or II cancer from which the patient is currently in complete remission",
                    "criterion": "stage I or II cancer",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "adequately treated"
                        },
                        {
                            "requirement_type": "remission status",
                            "expected_value": "complete remission"
                        }
                    ]
                },
                {
                    "exact_snippets": "any other cancer from which the patient has been disease free for five years",
                    "criterion": "any other cancer",
                    "requirements": [
                        {
                            "requirement_type": "disease-free duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 5,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 X institutional upper limit of normal or =< 5 X institutional upper limit of normal for patients with known liver metastasis",
            "criterions": [
                {
                    "exact_snippets": "Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 X institutional upper limit of normal",
                    "criterion": "aspartate aminotransferase (AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2.5,
                                        "unit": "X institutional upper limit of normal"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) ... =< 5 X institutional upper limit of normal for patients with known liver metastasis",
                    "criterion": "aspartate aminotransferase (AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "X institutional upper limit of normal"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "condition",
                            "expected_value": "known liver metastasis"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Tumor must be wild type for the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and BRAF oncogenes, and must have known PIK3CA, AKT mutation status and PTEN expression status",
            "criterions": [
                {
                    "exact_snippets": "Tumor must be wild type for the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS)",
                    "criterion": "KRAS oncogene",
                    "requirements": [
                        {
                            "requirement_type": "mutation status",
                            "expected_value": "wild type"
                        }
                    ]
                },
                {
                    "exact_snippets": "Tumor must be wild type for the ... BRAF oncogenes",
                    "criterion": "BRAF oncogene",
                    "requirements": [
                        {
                            "requirement_type": "mutation status",
                            "expected_value": "wild type"
                        }
                    ]
                },
                {
                    "exact_snippets": "Tumor must have known PIK3CA ... mutation status",
                    "criterion": "PIK3CA mutation",
                    "requirements": [
                        {
                            "requirement_type": "mutation status",
                            "expected_value": "known"
                        }
                    ]
                },
                {
                    "exact_snippets": "Tumor must have known ... AKT mutation status",
                    "criterion": "AKT mutation",
                    "requirements": [
                        {
                            "requirement_type": "mutation status",
                            "expected_value": "known"
                        }
                    ]
                },
                {
                    "exact_snippets": "Tumor must have known ... PTEN expression status",
                    "criterion": "PTEN expression",
                    "requirements": [
                        {
                            "requirement_type": "expression status",
                            "expected_value": "known"
                        }
                    ]
                }
            ]
        }
    ],
    "failed_exclusion": [
        {
            "line": "* Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study; if the patient has residual toxicity from prior treatment, toxicity must be =< grade 1 (or =< grade 2 for peripheral neuropathy and/or alopecia)",
            "criterions": [
                {
                    "exact_snippets": "Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study",
                    "criterion": "recent chemotherapy or radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "time since treatment for nitrosoureas or mitomycin C",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 6,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "if the patient has residual toxicity from prior treatment, toxicity must be =< grade 1",
                    "criterion": "residual toxicity from prior treatment",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 1,
                                        "unit": "grade"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "= < grade 2 for peripheral neuropathy and/or alopecia",
                    "criterion": "residual toxicity from prior treatment",
                    "requirements": [
                        {
                            "requirement_type": "severity for peripheral neuropathy and/or alopecia",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "grade"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who are receiving or have received any other investigational agents within 30 days of study day 1, or who have previously received MK-2206 at any time",
            "criterions": [
                {
                    "exact_snippets": "Patients who are receiving or have received any other investigational agents within 30 days of study day 1",
                    "criterion": "receipt of investigational agents",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 30,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "patients ... who have previously received MK-2206 at any time",
                    "criterion": "receipt of MK-2206",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "failed_miscellaneous": []
}