{
    "info": {
        "nct_id": "NCT01625520",
        "official_title": "Mono Centre, Open Label Proof of Concept Study SOM230 in Progressive Medullary Thyroid Cancer Patients and the Combination With RAD001 Upon Progression",
        "inclusion_criteria": "* Patients with progressive metastatic or postoperative persistent medullary thyroid cancer who have histopathologically confirmed disease and measurable tumor lesions. (Postoperative persistent after surgical removal is characterized by increased levels of calcitonin with or without radiological detectable tumour relapse or metastases.)\n* Patients with evidence of biochemical progression of disease, as expressed by progressive increase of serum calcitonin levels, assessed once a month for at least three months before study entry, according to RECIST definitions (elevation of the markers for at least 25 %).\n* Disease that is not amenable to surgery, radiation, or combined modality therapy with curative intent.\n* Adequate organ function - Karnofsky-Index performance status >60%\n* Life expectancy > 6 months\n* Age > 18 years\n* Women of childbearing potential must have a negative serum pregnancy test within 14 days of randomization and a urine pregnancy test 48 hours prior to the administration of the first study treatment.\n* Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary.\n* Signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the trial prior to enrolment.\nHealthy volunteers allowed\nMust have minimum age of 18 Years\nMust have maximum age of 80 Years",
        "exclusion_criteria": "* Unstable systemic diseases including uncontrolled hypertension, active uncontrolled infections, psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.\n* Known hypersensitivity to somatostatin analogues.\n* Pregnant or breast-feeding patients\n* Sign of recurrence of prior or concomitant malignancies (within the last 3 years or requiring active treatment) other than MTC; with the exception of previous basal cell skin cancer, previous cervical carcinoma in situ\n* Prior therapy with mTOR inhibitors (e.g. sirolimus, temsirolimus, everolimus)\n* Participation in a clinical trial to test an investigational drug within 4 weeks prior to visit 1.\n* Any of severe and/or uncontrolled medical conditions:\n* Patients who have congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction within the six months preceding enrollment,\n* QT related exclusion criteria\n* Previous treatments with chemotherapy, loco regional therapy (eg, chemoembolization) or interferon are permitted providing that toxicity has resolved to < Grade 1 at study entry and that last treatment was at least 4 weeks prior to baseline assessment.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Patients with progressive metastatic or postoperative persistent medullary thyroid cancer who have histopathologically confirmed disease and measurable tumor lesions. (Postoperative persistent after surgical removal is characterized by increased levels of calcitonin with or without radiological detectable tumour relapse or metastases.)",
            "criterions": [
                {
                    "exact_snippets": "progressive metastatic or postoperative persistent medullary thyroid cancer",
                    "criterion": "medullary thyroid cancer",
                    "requirements": [
                        {
                            "requirement_type": "progression",
                            "expected_value": [
                                "metastatic",
                                "postoperative persistent"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "histopathologically confirmed disease",
                    "criterion": "disease confirmation",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": "histopathological"
                        }
                    ]
                },
                {
                    "exact_snippets": "measurable tumor lesions",
                    "criterion": "tumor lesions",
                    "requirements": [
                        {
                            "requirement_type": "measurability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "increased levels of calcitonin",
                    "criterion": "calcitonin levels",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": "increased"
                        }
                    ]
                },
                {
                    "exact_snippets": "radiological detectable tumour relapse or metastases",
                    "criterion": "tumor relapse or metastases",
                    "requirements": [
                        {
                            "requirement_type": "detectability",
                            "expected_value": "radiological"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with evidence of biochemical progression of disease, as expressed by progressive increase of serum calcitonin levels, assessed once a month for at least three months before study entry, according to RECIST definitions (elevation of the markers for at least 25 %).",
            "criterions": [
                {
                    "exact_snippets": "evidence of biochemical progression of disease",
                    "criterion": "biochemical progression of disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "progressive increase of serum calcitonin levels",
                    "criterion": "serum calcitonin levels",
                    "requirements": [
                        {
                            "requirement_type": "trend",
                            "expected_value": "progressive increase"
                        }
                    ]
                },
                {
                    "exact_snippets": "assessed once a month for at least three months before study entry",
                    "criterion": "serum calcitonin levels assessment frequency",
                    "requirements": [
                        {
                            "requirement_type": "frequency",
                            "expected_value": "once a month for at least three months before study entry"
                        }
                    ]
                },
                {
                    "exact_snippets": "elevation of the markers for at least 25 %",
                    "criterion": "elevation of markers",
                    "requirements": [
                        {
                            "requirement_type": "percentage increase",
                            "expected_value": {
                                "operator": ">=",
                                "value": 25,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Disease that is not amenable to surgery, radiation, or combined modality therapy with curative intent.",
            "criterions": [
                {
                    "exact_snippets": "Disease that is not amenable to surgery",
                    "criterion": "disease amenability to surgery",
                    "requirements": [
                        {
                            "requirement_type": "amenability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Disease that is not amenable to ... radiation",
                    "criterion": "disease amenability to radiation",
                    "requirements": [
                        {
                            "requirement_type": "amenability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Disease that is not amenable to ... combined modality therapy with curative intent",
                    "criterion": "disease amenability to combined modality therapy with curative intent",
                    "requirements": [
                        {
                            "requirement_type": "amenability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate organ function - Karnofsky-Index performance status >60%",
            "criterions": [
                {
                    "exact_snippets": "Adequate organ function",
                    "criterion": "organ function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Karnofsky-Index performance status >60%",
                    "criterion": "Karnofsky-Index performance status",
                    "requirements": [
                        {
                            "requirement_type": "performance status",
                            "expected_value": {
                                "operator": ">",
                                "value": 60,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Life expectancy > 6 months",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy > 6 months",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Age > 18 years",
            "criterions": [
                {
                    "exact_snippets": "Age > 18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women of childbearing potential must have a negative serum pregnancy test within 14 days of randomization and a urine pregnancy test 48 hours prior to the administration of the first study treatment.",
            "criterions": [
                {
                    "exact_snippets": "Women of childbearing potential",
                    "criterion": "childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "negative serum pregnancy test within 14 days of randomization",
                    "criterion": "serum pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        },
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 14 days of randomization"
                        }
                    ]
                },
                {
                    "exact_snippets": "urine pregnancy test 48 hours prior to the administration of the first study treatment",
                    "criterion": "urine pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "48 hours prior to the administration of the first study treatment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary.",
            "criterions": [
                {
                    "exact_snippets": "known history of impaired fasting glucose",
                    "criterion": "impaired fasting glucose",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "known history of ... diabetes mellitus (DM)",
                    "criterion": "diabetes mellitus (DM)",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "blood glucose ... must be monitored closely",
                    "criterion": "blood glucose",
                    "requirements": [
                        {
                            "requirement_type": "monitoring",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "antidiabetic treatment must be monitored closely",
                    "criterion": "antidiabetic treatment",
                    "requirements": [
                        {
                            "requirement_type": "monitoring",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the trial prior to enrolment.",
            "criterions": [
                {
                    "exact_snippets": "Signed and dated informed consent document",
                    "criterion": "informed 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"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have maximum age of 80 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 80 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 80,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "* Unstable systemic diseases including uncontrolled hypertension, active uncontrolled infections, psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.",
            "criterions": [
                {
                    "exact_snippets": "Unstable systemic diseases including uncontrolled hypertension",
                    "criterion": "systemic diseases",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": "unstable"
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled hypertension",
                    "criterion": "hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "active uncontrolled infections",
                    "criterion": "infections",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "psychiatric condition",
                    "criterion": "psychiatric condition",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "laboratory abnormality",
                    "criterion": "laboratory abnormality",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known hypersensitivity to somatostatin analogues.",
            "criterions": [
                {
                    "exact_snippets": "Known hypersensitivity to somatostatin analogues.",
                    "criterion": "hypersensitivity to somatostatin analogues",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant or breast-feeding patients",
            "criterions": [
                {
                    "exact_snippets": "Pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "breast-feeding",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Sign of recurrence of prior or concomitant malignancies (within the last 3 years or requiring active treatment) other than MTC; with the exception of previous basal cell skin cancer, previous cervical carcinoma in situ",
            "criterions": [
                {
                    "exact_snippets": "Sign of recurrence of prior or concomitant malignancies",
                    "criterion": "recurrence of malignancies",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "within the last 3 years",
                    "criterion": "recurrence of malignancies",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "requiring active treatment",
                    "criterion": "recurrence of malignancies",
                    "requirements": [
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "other than MTC",
                    "criterion": "type of malignancy",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": "MTC"
                        }
                    ]
                },
                {
                    "exact_snippets": "with the exception of previous basal cell skin cancer, previous cervical carcinoma in situ",
                    "criterion": "type of malignancy",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": [
                                "basal cell skin cancer",
                                "cervical carcinoma in situ"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior therapy with mTOR inhibitors (e.g. sirolimus, temsirolimus, everolimus)",
            "criterions": [
                {
                    "exact_snippets": "Prior therapy with mTOR inhibitors (e.g. sirolimus, temsirolimus, everolimus)",
                    "criterion": "mTOR inhibitors therapy",
                    "requirements": [
                        {
                            "requirement_type": "prior therapy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participation in a clinical trial to test an investigational drug within 4 weeks prior to visit 1.",
            "criterions": [
                {
                    "exact_snippets": "Participation in a clinical trial to test an investigational drug within 4 weeks prior to visit 1.",
                    "criterion": "participation in a clinical trial",
                    "requirements": [
                        {
                            "requirement_type": "time since participation",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any of severe and/or uncontrolled medical conditions:",
            "criterions": [
                {
                    "exact_snippets": "severe and/or uncontrolled medical conditions",
                    "criterion": "medical conditions",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        },
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction within the six months preceding enrollment,",
            "criterions": [
                {
                    "exact_snippets": "congestive heart failure (NYHA Class III or IV)",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "NYHA Class III",
                                "NYHA Class IV"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "unstable angina",
                    "criterion": "unstable angina",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "sustained ventricular tachycardia",
                    "criterion": "sustained ventricular tachycardia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ventricular fibrillation",
                    "criterion": "ventricular fibrillation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "clinically significant bradycardia",
                    "criterion": "clinically significant bradycardia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "advanced heart block",
                    "criterion": "advanced heart block",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of acute myocardial infarction within the six months preceding enrollment",
                    "criterion": "acute myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* QT related exclusion criteria",
            "criterions": [
                {
                    "exact_snippets": "QT related exclusion criteria",
                    "criterion": "QT interval",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Previous treatments with chemotherapy, loco regional therapy (eg, chemoembolization) or interferon are permitted providing that toxicity has resolved to < Grade 1 at study entry and that last treatment was at least 4 weeks prior to baseline assessment.",
            "criterions": [
                {
                    "exact_snippets": "Previous treatments with chemotherapy, loco regional therapy (eg, chemoembolization) or interferon are permitted",
                    "criterion": "previous treatments",
                    "requirements": [
                        {
                            "requirement_type": "types",
                            "expected_value": [
                                "chemotherapy",
                                "loco regional therapy",
                                "interferon"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "toxicity has resolved to < Grade 1 at study entry",
                    "criterion": "toxicity",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<",
                                "value": 1,
                                "unit": "Grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "last treatment was at least 4 weeks prior to baseline assessment",
                    "criterion": "time since last treatment",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}