{
    "info": {
        "nct_id": "NCT02366819",
        "official_title": "PERIOP-FOLFIRINOX: A Pilot Trial of Perioperative Genotype-guided Irinotecan Dosing of gFOLFIRINOX for Locally Advanced Gastroesophageal Adenocarcinoma",
        "inclusion_criteria": "* Histologically confirmed locally advanced gastric (primary endpoint includes proximal and mid-body stomach) or esophagogastric adenocarcinoma; distal gastric (antral) adenocarcinomas are eligible for enrolment but will not be included in the primary analysis\n* Locally advanced disease as determined by endoscopic ultrasound (EUS) stage > primary tumor (T) 3 and/or any T, lymph nodes (N)+ disease without metastatic disease (Mx)\n* All patients must have diagnostic laparoscopy with diagnostic washings for cytology; both cytology positive and negative patients are eligible for enrolment, but only cytology negative patients will be included in the primary analyses; gross peritoneal disease is not eligible\n* Eastern Cooperative Oncology Group (ECOG) performance status =< 1\n* Eligible for surgery with curative intent\n* Absolute neutrophil count (ANC) >= 1250/ul\n* Hemoglobin >= 9 g/dL\n* Platelets >= 100,000/ul\n* Total bilirubin < 1.5 x upper limit of normal\n* Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) < 2.5 x upper limit of normal for patients without liver metastases OR SGOT and SGPT < 5 x upper limit of normal for patients with liver metastases\n* Creatinine =< 1.5 x upper limit of normal\n* Measurable or non-measurable disease by Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 will be allowed\n* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, up until 30 days after final study treatment; should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately\n* Patients taking substrates, inhibitors, or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) should be encouraged to switch to alternative drugs whenever possible, given the potential for drug-drug interactions with irinotecan\n* Signed informed consent\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Previous or concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or any other cancer for which the patient has been previously treated and the lifetime recurrence risk is less than 30%\n* Inflammatory bowel disease that is uncontrolled or on active treatment (Crohn's disease, ulcerative colitis)\n* Diarrhea, grade 1 or greater by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version [v] 4.0)\n* Neuropathy, grade 2 or greater by NCI-CTCAE, v 4.0\n* Serious underlying medical or psychiatric illnesses that would, in the opinion of the treating physician, substantially increase the risk for complications related to treatment\n* Active uncontrolled bleeding\n* Pregnancy or breastfeeding\n* Major surgery within 4 weeks\n* Patients with any polymorphism in UGT1A1 other than *1 or *28 (e.g, *6) will be allowed and treated as in the *28/*28 dosing group",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Histologically confirmed locally advanced gastric (primary endpoint includes proximal and mid-body stomach) or esophagogastric adenocarcinoma; distal gastric (antral) adenocarcinomas are eligible for enrolment but will not be included in the primary analysis",
            "criterions": [
                {
                    "exact_snippets": [
                        "Histologically confirmed"
                    ],
                    "criterion": "gastric or esophagogastric adenocarcinoma",
                    "requirement_type": "confirmation method",
                    "expected_value": "histologically"
                },
                {
                    "exact_snippets": [
                        "locally advanced"
                    ],
                    "criterion": "gastric or esophagogastric adenocarcinoma",
                    "requirement_type": "stage",
                    "expected_value": "locally advanced"
                },
                {
                    "exact_snippets": [
                        "proximal and mid-body stomach"
                    ],
                    "criterion": "gastric adenocarcinoma",
                    "requirement_type": "location",
                    "expected_value": [
                        "proximal",
                        "mid-body"
                    ]
                },
                {
                    "exact_snippets": [
                        "distal gastric (antral) adenocarcinomas"
                    ],
                    "criterion": "gastric adenocarcinoma",
                    "requirement_type": "location",
                    "expected_value": "distal (antral)"
                }
            ]
        },
        {
            "line": "* Locally advanced disease as determined by endoscopic ultrasound (EUS) stage > primary tumor (T) 3 and/or any T, lymph nodes (N)+ disease without metastatic disease (Mx)",
            "criterions": [
                {
                    "exact_snippets": [
                        "Locally advanced disease",
                        "endoscopic ultrasound (EUS) stage > primary tumor (T) 3"
                    ],
                    "criterion": "primary tumor stage",
                    "requirement_type": "comparison",
                    "expected_value": {
                        "operator": ">",
                        "value": 3
                    }
                },
                {
                    "exact_snippets": [
                        "Locally advanced disease",
                        "endoscopic ultrasound (EUS) stage",
                        "lymph nodes (N)+ disease"
                    ],
                    "criterion": "lymph nodes",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Locally advanced disease",
                        "without metastatic disease (Mx)"
                    ],
                    "criterion": "metastatic disease",
                    "requirement_type": "presence",
                    "expected_value": false
                }
            ]
        },
        {
            "line": "* All patients must have diagnostic laparoscopy with diagnostic washings for cytology; both cytology positive and negative patients are eligible for enrolment, but only cytology negative patients will be included in the primary analyses; gross peritoneal disease is not eligible",
            "criterions": [
                {
                    "exact_snippets": [
                        "diagnostic laparoscopy"
                    ],
                    "criterion": "diagnostic laparoscopy",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "diagnostic washings for cytology"
                    ],
                    "criterion": "diagnostic washings for cytology",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "cytology positive and negative patients are eligible for enrolment"
                    ],
                    "criterion": "cytology result",
                    "requirement_type": "eligibility for enrolment",
                    "expected_value": [
                        "positive",
                        "negative"
                    ]
                },
                {
                    "exact_snippets": [
                        "only cytology negative patients will be included in the primary analyses"
                    ],
                    "criterion": "cytology result",
                    "requirement_type": "inclusion in primary analyses",
                    "expected_value": "negative"
                },
                {
                    "exact_snippets": [
                        "gross peritoneal disease is not eligible"
                    ],
                    "criterion": "gross peritoneal disease",
                    "requirement_type": "eligibility",
                    "expected_value": false
                }
            ]
        },
        {
            "line": "* Eastern Cooperative Oncology Group (ECOG) performance status =< 1",
            "criterions": [
                {
                    "exact_snippets": [
                        "Eastern Cooperative Oncology Group (ECOG) performance status =< 1"
                    ],
                    "criterion": "ECOG performance status",
                    "requirement_type": "value",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 1
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Eligible for surgery with curative intent",
            "criterions": [
                {
                    "exact_snippets": [
                        "Eligible for surgery"
                    ],
                    "criterion": "surgery",
                    "requirement_type": "eligibility",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "curative intent"
                    ],
                    "criterion": "surgery",
                    "requirement_type": "intent",
                    "expected_value": "curative"
                }
            ]
        },
        {
            "line": "* Absolute neutrophil count (ANC) >= 1250/ul",
            "criterions": [
                {
                    "exact_snippets": [
                        "Absolute neutrophil count (ANC) >= 1250/ul"
                    ],
                    "criterion": "absolute neutrophil count",
                    "requirement_type": "quantity",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 1250
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Hemoglobin >= 9 g/dL",
            "criterions": [
                {
                    "exact_snippets": [
                        "Hemoglobin >= 9 g/dL"
                    ],
                    "criterion": "hemoglobin",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 9
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Platelets >= 100,000/ul",
            "criterions": [
                {
                    "exact_snippets": [
                        "Platelets >= 100,000/ul"
                    ],
                    "criterion": "platelets",
                    "requirement_type": "count",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 100000
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Total bilirubin < 1.5 x upper limit of normal",
            "criterions": [
                {
                    "exact_snippets": [
                        "Total bilirubin < 1.5 x upper limit of normal"
                    ],
                    "criterion": "total bilirubin",
                    "requirement_type": "quantity",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<",
                                "value": 1.5
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Creatinine =< 1.5 x upper limit of normal",
            "criterions": [
                {
                    "exact_snippets": [
                        "Creatinine =< 1.5 x upper limit of normal"
                    ],
                    "criterion": "creatinine",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 1.5
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Measurable or non-measurable disease by Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 will be allowed",
            "criterions": [
                {
                    "exact_snippets": [
                        "Measurable",
                        "disease"
                    ],
                    "criterion": "disease",
                    "requirement_type": "measurability",
                    "expected_value": "measurable"
                },
                {
                    "exact_snippets": [
                        "non-measurable",
                        "disease"
                    ],
                    "criterion": "disease",
                    "requirement_type": "measurability",
                    "expected_value": "non-measurable"
                }
            ]
        },
        {
            "line": "* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, up until 30 days after final study treatment; should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately",
            "criterions": [
                {
                    "exact_snippets": [
                        "Women of child-bearing potential"
                    ],
                    "criterion": "women of child-bearing potential",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "men must agree to use adequate contraception"
                    ],
                    "criterion": "contraception use",
                    "requirement_type": "agreement",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "adequate contraception (hormonal or barrier method of birth control; abstinence)"
                    ],
                    "criterion": "contraception method",
                    "requirement_type": "type",
                    "expected_value": [
                        "hormonal",
                        "barrier method",
                        "abstinence"
                    ]
                },
                {
                    "exact_snippets": [
                        "prior to study entry and for the duration of study participation, up until 30 days after final study treatment"
                    ],
                    "criterion": "contraception duration",
                    "requirement_type": "time period",
                    "expected_value": "prior to study entry and for the duration of study participation, up until 30 days after final study treatment"
                },
                {
                    "exact_snippets": [
                        "should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately"
                    ],
                    "criterion": "pregnancy",
                    "requirement_type": "notification",
                    "expected_value": "inform treating physician immediately"
                }
            ]
        },
        {
            "line": "* Patients taking substrates, inhibitors, or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) should be encouraged to switch to alternative drugs whenever possible, given the potential for drug-drug interactions with irinotecan",
            "criterions": [
                {
                    "exact_snippets": [
                        "Patients taking substrates, inhibitors, or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)"
                    ],
                    "criterion": "CYP3A4 substrates, inhibitors, or inducers",
                    "requirement_type": "use",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "potential for drug-drug interactions with irinotecan"
                    ],
                    "criterion": "drug-drug interactions with irinotecan",
                    "requirement_type": "potential",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* Signed informed consent",
            "criterions": [
                {
                    "exact_snippets": [
                        "Signed informed consent"
                    ],
                    "criterion": "informed consent",
                    "requirement_type": "signed",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": [
                        "Healthy volunteers allowed"
                    ],
                    "criterion": "healthy volunteers",
                    "requirement_type": "participation",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": [
                        "minimum age of 18 Years"
                    ],
                    "criterion": "age",
                    "requirement_type": "minimum",
                    "expected_value": {
                        "operator": ">=",
                        "value": 18
                    }
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "* Previous or concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or any other cancer for which the patient has been previously treated and the lifetime recurrence risk is less than 30%",
            "criterions": [
                {
                    "exact_snippets": [
                        "Previous or concurrent malignancy"
                    ],
                    "criterion": "malignancy",
                    "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",
                    "requirement_type": "treatment status",
                    "expected_value": "adequately treated"
                },
                {
                    "exact_snippets": [
                        "in situ cervical cancer"
                    ],
                    "criterion": "cervical cancer",
                    "requirement_type": "stage",
                    "expected_value": "in situ"
                },
                {
                    "exact_snippets": [
                        "any other cancer for which the patient has been previously treated"
                    ],
                    "criterion": "other cancer",
                    "requirement_type": "treatment status",
                    "expected_value": "previously treated"
                },
                {
                    "exact_snippets": [
                        "lifetime recurrence risk is less than 30%"
                    ],
                    "criterion": "cancer recurrence risk",
                    "requirement_type": "risk level",
                    "expected_value": {
                        "operator": "<",
                        "value": 30
                    }
                }
            ]
        },
        {
            "line": "* Inflammatory bowel disease that is uncontrolled or on active treatment (Crohn's disease, ulcerative colitis)",
            "criterions": [
                {
                    "exact_snippets": [
                        "Inflammatory bowel disease",
                        "uncontrolled"
                    ],
                    "criterion": "inflammatory bowel disease",
                    "requirement_type": "control status",
                    "expected_value": "uncontrolled"
                },
                {
                    "exact_snippets": [
                        "Inflammatory bowel disease",
                        "on active treatment"
                    ],
                    "criterion": "inflammatory bowel disease",
                    "requirement_type": "treatment status",
                    "expected_value": "on active treatment"
                },
                {
                    "exact_snippets": [
                        "Crohn's disease"
                    ],
                    "criterion": "Crohn's disease",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "ulcerative colitis"
                    ],
                    "criterion": "ulcerative colitis",
                    "requirement_type": "presence",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* Diarrhea, grade 1 or greater by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version [v] 4.0)",
            "criterions": [
                {
                    "exact_snippets": [
                        "Diarrhea, grade 1 or greater",
                        "National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version [v] 4.0)"
                    ],
                    "criterion": "diarrhea",
                    "requirement_type": "severity",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 1
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Neuropathy, grade 2 or greater by NCI-CTCAE, v 4.0",
            "criterions": [
                {
                    "exact_snippets": [
                        "Neuropathy"
                    ],
                    "criterion": "neuropathy",
                    "requirement_type": "severity",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 2
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "NCI-CTCAE, v 4.0"
                    ],
                    "criterion": "NCI-CTCAE version",
                    "requirement_type": "version",
                    "expected_value": "4.0"
                }
            ]
        },
        {
            "line": "* Serious underlying medical or psychiatric illnesses that would, in the opinion of the treating physician, substantially increase the risk for complications related to treatment",
            "criterions": [
                {
                    "exact_snippets": [
                        "Serious underlying medical or psychiatric illnesses"
                    ],
                    "criterion": "underlying medical or psychiatric illnesses",
                    "requirement_type": "severity",
                    "expected_value": "serious"
                },
                {
                    "exact_snippets": [
                        "in the opinion of the treating physician, substantially increase the risk for complications related to treatment"
                    ],
                    "criterion": "risk for complications related to treatment",
                    "requirement_type": "increase",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* Active uncontrolled bleeding",
            "criterions": [
                {
                    "exact_snippets": [
                        "Active uncontrolled bleeding"
                    ],
                    "criterion": "bleeding",
                    "requirement_type": "control",
                    "expected_value": false
                }
            ]
        },
        {
            "line": "* Pregnancy or breastfeeding",
            "criterions": [
                {
                    "exact_snippets": [
                        "Pregnancy"
                    ],
                    "criterion": "pregnancy",
                    "requirement_type": "status",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "breastfeeding"
                    ],
                    "criterion": "breastfeeding",
                    "requirement_type": "status",
                    "expected_value": false
                }
            ]
        },
        {
            "line": "* Major surgery within 4 weeks",
            "criterions": [
                {
                    "exact_snippets": [
                        "Major surgery within 4 weeks"
                    ],
                    "criterion": "major surgery",
                    "requirement_type": "time since",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 4
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Patients with any polymorphism in UGT1A1 other than *1 or *28 (e.g, *6) will be allowed and treated as in the *28/*28 dosing group",
            "criterions": [
                {
                    "exact_snippets": [
                        "any polymorphism in UGT1A1 other than *1 or *28"
                    ],
                    "criterion": "UGT1A1 polymorphism",
                    "requirement_type": "specificity",
                    "expected_value": [
                        "*1",
                        "*28"
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "* Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) < 2.5 x upper limit of normal for patients without liver metastases OR SGOT and SGPT < 5 x upper limit of normal for patients with liver metastases",
            "criterions": [
                {
                    "exact_snippets": [
                        "Serum glutamic oxaloacetic transaminase (SGOT)",
                        "< 2.5 x upper limit of normal",
                        "patients without liver metastases"
                    ],
                    "criterion": "SGOT",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<",
                                "value": 2.5
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "Serum glutamate pyruvate transaminase (SGPT)",
                        "< 2.5 x upper limit of normal",
                        "patients without liver metastases"
                    ],
                    "criterion": "SGPT",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<",
                                "value": 2.5
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "SGOT",
                        "< 5 x upper limit of normal",
                        "patients with liver metastases"
                    ],
                    "criterion": "SGOT",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<",
                                "value": 5
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "SGPT",
                        "< 5 x upper limit of normal",
                        "patients with liver metastases"
                    ],
                    "criterion": "SGPT",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<",
                                "value": 5
                            }
                        ]
                    }
                }
            ]
        }
    ],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}