{
    "info": {
        "nct_id": "NCT03084757",
        "official_title": "SHIVA02 - Evaluation of the Efficacy of Targeted Therapy Based on Tumor Molecular Profiling in Patients With Advanced Cancer Using Each Patient as Its Own Control",
        "inclusion_criteria": "Healthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "",
        "miscellaneous_criteria": "Inclusion criteria:\n\nInclusion will proceed in 2 steps. First step for molecular analyses and second step in order to be included in the efficacy analysis.\n\nInclusion criteria for Step 1:\n\n1. Patient with recurrent/metastatic solid tumor who failed or are not candidate for treatments usually proposed in first intention and for whom a prospective clinical trial has been indicated in a tumor board\n2. Patient with a documented progression before the start of conventional therapy according to RECIST 1.1.\n3. Patient ≥18 years old\n\n3) Disease amenable to biopsy 5) ECOG performance status of 0 or 1 6) Measurable disease 7) Adequate renal function defined by a serum creatinine <1.5xUNL (upper normal limit) 8) Adequate liver function test defined by SGOT & SGPT <3xUNL (5xUNL in case of liver metastases), and bilirubin level <1.5xUNL 9) Adequate bone marrow function defined by platelets >100,000/mm3, hemoglobin >9 g/dL, and neutrophils >1,000/mm3 10) Patient must be affiliated to the French Social Security System 11) Signed informed consent 12 For female of child-bearing potential: a negative pregnancy test <72 hours before starting study treatment is required. If sexually active, female of childbearing potential must use \"highly effective\" methods of contraception for the study duration and for 3 months following the last treatment 13) For male of reproductive potential: any sexually active male patient must use a condom while on study treatment and for 3 months following the last treatment\n\nInclusion criteria for Step 2:\n\n1. Patient for whom the Molecular Biology Board (MBB) has identified a druggable molecular alteration of the RAF/MEK signaling pathway and a treatment recommendation has been established by the MBB.\n2. Patient with a documented progression during the conventional therapy according to RECIST 1.1.\n3. Patient with imaging performed within 28 days prior to the planned start date of treatment\n\nExclusion criteria:\n\n1. Patients below 18 years old\n2. Patients with CNS involvement that has not been controlled for >3 months\n3. Patients planned to receive a molecularly targeted agent\n4. Patients who are candidate to receive a molecularly targeted agent that is approved for their disease\n5. Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, including uncontrolled diabetes, cardiac disease, uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infection within one year, chronic liver or renal disease, active gastrointestinal tract ulceration, severely impaired lung function\n6. Pregnant and/or breastfeeding women\n7. Patients individually deprived of liberty or placed under the authority of a tutor\n8. Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule\n9. Known HIV, HBV, or HCV infection"
    },
    "inclusion_lines": [
        {
            "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": [],
    "miscellaneous_lines": [
        {
            "line": "Inclusion will proceed in 2 steps. First step for molecular analyses and second step in order to be included in the efficacy analysis.",
            "criterions": [
                {
                    "exact_snippets": "molecular analyses",
                    "criterion": "molecular analyses",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "efficacy analysis",
                    "criterion": "efficacy analysis",
                    "requirements": [
                        {
                            "requirement_type": "inclusion",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Patient with recurrent/metastatic solid tumor who failed or are not candidate for treatments usually proposed in first intention and for whom a prospective clinical trial has been indicated in a tumor board",
            "criterions": [
                {
                    "exact_snippets": "recurrent/metastatic solid tumor",
                    "criterion": "solid tumor",
                    "requirements": [
                        {
                            "requirement_type": "recurrence/metastasis",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "failed or are not candidate for treatments usually proposed in first intention",
                    "criterion": "treatment candidacy",
                    "requirements": [
                        {
                            "requirement_type": "failure",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "candidacy",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "prospective clinical trial has been indicated in a tumor board",
                    "criterion": "clinical trial indication",
                    "requirements": [
                        {
                            "requirement_type": "indication",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Patient with a documented progression before the start of conventional therapy according to RECIST 1.1.",
            "criterions": [
                {
                    "exact_snippets": "documented progression before the start of conventional therapy",
                    "criterion": "disease progression",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "timing",
                            "expected_value": "before the start of conventional therapy"
                        }
                    ]
                },
                {
                    "exact_snippets": "according to RECIST 1.1",
                    "criterion": "RECIST 1.1 criteria",
                    "requirements": [
                        {
                            "requirement_type": "compliance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patient ≥18 years old",
            "criterions": [
                {
                    "exact_snippets": "Patient ≥18 years old",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3) Disease amenable to biopsy 5) ECOG performance status of 0 or 1 6) Measurable disease 7) Adequate renal function defined by a serum creatinine <1.5xUNL (upper normal limit) 8) Adequate liver function test defined by SGOT & SGPT <3xUNL (5xUNL in case of liver metastases), and bilirubin level <1.5xUNL 9) Adequate bone marrow function defined by platelets >100,000/mm3, hemoglobin >9 g/dL, and neutrophils >1,000/mm3 10) Patient must be affiliated to the French Social Security System 11) Signed informed consent 12 For female of child-bearing potential: a negative pregnancy test <72 hours before starting study treatment is required. If sexually active, female of childbearing potential must use \"highly effective\" methods of contraception for the study duration and for 3 months following the last treatment 13) For male of reproductive potential: any sexually active male patient must use a condom while on study treatment and for 3 months following the last treatment",
            "criterions": [
                {
                    "exact_snippets": "Disease amenable to biopsy",
                    "criterion": "disease amenability to biopsy",
                    "requirements": [
                        {
                            "requirement_type": "amenability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ECOG performance status of 0 or 1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "=",
                                        "value": 1,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Measurable disease",
                    "criterion": "measurable disease",
                    "requirements": [
                        {
                            "requirement_type": "measurability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate renal function defined by a serum creatinine <1.5xUNL",
                    "criterion": "renal function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "serum creatinine",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "xUNL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate liver function test defined by SGOT & SGPT <3xUNL (5xUNL in case of liver metastases), and bilirubin level <1.5xUNL",
                    "criterion": "liver function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "SGOT & SGPT",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "xUNL"
                            }
                        },
                        {
                            "requirement_type": "SGOT & SGPT in case of liver metastases",
                            "expected_value": {
                                "operator": "<",
                                "value": 5,
                                "unit": "xUNL"
                            }
                        },
                        {
                            "requirement_type": "bilirubin level",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "xUNL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate bone marrow function defined by platelets >100,000/mm3, hemoglobin >9 g/dL, and neutrophils >1,000/mm3",
                    "criterion": "bone marrow function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "platelets",
                            "expected_value": {
                                "operator": ">",
                                "value": 100000,
                                "unit": "mm3"
                            }
                        },
                        {
                            "requirement_type": "hemoglobin",
                            "expected_value": {
                                "operator": ">",
                                "value": 9,
                                "unit": "g/dL"
                            }
                        },
                        {
                            "requirement_type": "neutrophils",
                            "expected_value": {
                                "operator": ">",
                                "value": 1000,
                                "unit": "mm3"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Patient must be affiliated to the French Social Security System",
                    "criterion": "affiliation to the French Social Security System",
                    "requirements": [
                        {
                            "requirement_type": "affiliation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Signed informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "signed",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "For female of child-bearing potential: a negative pregnancy test <72 hours before starting study treatment is required",
                    "criterion": "pregnancy test for females of child-bearing potential",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        },
                        {
                            "requirement_type": "timing",
                            "expected_value": "<72 hours before starting study treatment"
                        }
                    ]
                },
                {
                    "exact_snippets": "If sexually active, female of childbearing potential must use \"highly effective\" methods of contraception for the study duration and for 3 months following the last treatment",
                    "criterion": "contraception for sexually active females of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "highly effective"
                        },
                        {
                            "requirement_type": "duration",
                            "expected_value": "for the study duration and for 3 months following the last treatment"
                        }
                    ]
                },
                {
                    "exact_snippets": "For male of reproductive potential: any sexually active male patient must use a condom while on study treatment and for 3 months following the last treatment",
                    "criterion": "contraception for sexually active males of reproductive potential",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "condom"
                        },
                        {
                            "requirement_type": "duration",
                            "expected_value": "while on study treatment and for 3 months following the last treatment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Patient for whom the Molecular Biology Board (MBB) has identified a druggable molecular alteration of the RAF/MEK signaling pathway and a treatment recommendation has been established by the MBB.",
            "criterions": [
                {
                    "exact_snippets": "Molecular Biology Board (MBB) has identified a druggable molecular alteration of the RAF/MEK signaling pathway",
                    "criterion": "druggable molecular alteration of the RAF/MEK signaling pathway",
                    "requirements": [
                        {
                            "requirement_type": "identification",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "treatment recommendation has been established by the MBB",
                    "criterion": "treatment recommendation by the MBB",
                    "requirements": [
                        {
                            "requirement_type": "establishment",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Patient with a documented progression during the conventional therapy according to RECIST 1.1.",
            "criterions": [
                {
                    "exact_snippets": "documented progression during the conventional therapy",
                    "criterion": "disease progression",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "timing",
                            "expected_value": "during conventional therapy"
                        }
                    ]
                },
                {
                    "exact_snippets": "according to RECIST 1.1",
                    "criterion": "RECIST 1.1 criteria",
                    "requirements": [
                        {
                            "requirement_type": "compliance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patient with imaging performed within 28 days prior to the planned start date of treatment",
            "criterions": [
                {
                    "exact_snippets": "imaging performed within 28 days prior to the planned start date of treatment",
                    "criterion": "imaging",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Patients below 18 years old",
            "criterions": [
                {
                    "exact_snippets": "Patients below 18 years old",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Patients with CNS involvement that has not been controlled for >3 months",
            "criterions": [
                {
                    "exact_snippets": "CNS involvement",
                    "criterion": "CNS involvement",
                    "requirements": [
                        {
                            "requirement_type": "control duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patients planned to receive a molecularly targeted agent",
            "criterions": [
                {
                    "exact_snippets": "Patients planned to receive a molecularly targeted agent",
                    "criterion": "planned treatment",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": "molecularly targeted agent"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Patients who are candidate to receive a molecularly targeted agent that is approved for their disease",
            "criterions": [
                {
                    "exact_snippets": "Patients who are candidate to receive a molecularly targeted agent",
                    "criterion": "candidate for molecularly targeted agent",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "agent that is approved for their disease",
                    "criterion": "agent approval for disease",
                    "requirements": [
                        {
                            "requirement_type": "approval",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, including uncontrolled diabetes, cardiac disease, uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infection within one year, chronic liver or renal disease, active gastrointestinal tract ulceration, severely impaired lung function",
            "criterions": [
                {
                    "exact_snippets": "other concurrent severe and/or uncontrolled medical disease",
                    "criterion": "concurrent medical disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        },
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled diabetes",
                    "criterion": "diabetes",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "cardiac disease",
                    "criterion": "cardiac disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled hypertension",
                    "criterion": "hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "congestive cardiac failure",
                    "criterion": "congestive cardiac failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ventricular arrhythmias",
                    "criterion": "ventricular arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "active ischemic heart disease",
                    "criterion": "ischemic heart disease",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "myocardial infection within one year",
                    "criterion": "myocardial infection",
                    "requirements": [
                        {
                            "requirement_type": "time since occurrence",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "year"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "chronic liver or renal disease",
                    "criterion": "chronic liver or renal disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "active gastrointestinal tract ulceration",
                    "criterion": "gastrointestinal tract ulceration",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "severely impaired lung function",
                    "criterion": "lung function",
                    "requirements": [
                        {
                            "requirement_type": "impairment",
                            "expected_value": "severe"
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Pregnant and/or breastfeeding women",
            "criterions": [
                {
                    "exact_snippets": "Pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "breastfeeding women",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Patients individually deprived of liberty or placed under the authority of a tutor",
            "criterions": [
                {
                    "exact_snippets": "Patients individually deprived of liberty",
                    "criterion": "deprivation of liberty",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "placed under the authority of a tutor",
                    "criterion": "authority of a tutor",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule",
            "criterions": [
                {
                    "exact_snippets": "psychological ... condition potentially hampering compliance",
                    "criterion": "psychological condition",
                    "requirements": [
                        {
                            "requirement_type": "impact on compliance",
                            "expected_value": "potentially hampering"
                        }
                    ]
                },
                {
                    "exact_snippets": "familial ... condition potentially hampering compliance",
                    "criterion": "familial condition",
                    "requirements": [
                        {
                            "requirement_type": "impact on compliance",
                            "expected_value": "potentially hampering"
                        }
                    ]
                },
                {
                    "exact_snippets": "sociological ... condition potentially hampering compliance",
                    "criterion": "sociological condition",
                    "requirements": [
                        {
                            "requirement_type": "impact on compliance",
                            "expected_value": "potentially hampering"
                        }
                    ]
                },
                {
                    "exact_snippets": "geographical condition potentially hampering compliance",
                    "criterion": "geographical condition",
                    "requirements": [
                        {
                            "requirement_type": "impact on compliance",
                            "expected_value": "potentially hampering"
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Known HIV, HBV, or HCV infection",
            "criterions": [
                {
                    "exact_snippets": "Known HIV",
                    "criterion": "HIV infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "HBV",
                    "criterion": "HBV infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "HCV infection",
                    "criterion": "HCV infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": [
        {
            "line": "Inclusion criteria:",
            "criterions": []
        },
        {
            "line": "Inclusion criteria for Step 1:",
            "criterions": []
        },
        {
            "line": "Inclusion criteria for Step 2:",
            "criterions": []
        },
        {
            "line": "Exclusion criteria:",
            "criterions": []
        }
    ]
}