{
    "info": {
        "nct_id": "NCT02269982",
        "official_title": "Development of Circulating Molecular Predictors of Chemotherapy and Novel Hormonal Therapy Benefit in Men With Metastatic Castration Resistant Prostate Cancer (mCRPC)",
        "inclusion_criteria": "1. Histologically confirmed diagnosis of adenocarcinoma of the prostate. Pure small cell or neuroendocrine tumors of the prostate are not permitted.\n2. Clinical or radiographic evidence of metastatic disease.\n3. Planned therapy with either enzalutamide and/or abiraterone acetate within the coming 6 weeks\n4. Castrate levels of testosterone (<50 ng/dl) at most recent assessment and/or documented ongoing Androgen Deprivation Therapy for at lease three months.\n5. Evidence of disease progression on or following most recent therapy as evidenced by at least one of the following:\n\n   * Radiographic evidence of disease progression as defined by one or more new bone scan lesions that is not consistent with flare/healing, or growth of soft tissue/visceral metastases to greater than one centimeter (cm) in longest diameter (2 cm shortest diameter for lymph nodes).\n   * Clinical progression as defined by the treating physician (such as pain progression)\n   * Consecutive PSA rises meeting PSA progression criteria as determined by PCWG2 criteria (increase that is >25% and >2 ng/mL above the nadir, and which is confirmed by a second value 3 or more weeks later)\n6. At least two of the following high risk features during screening for rapid disease progression:\n\n   1. Anemia with a hemoglobin <12.0 g/dl\n   2. Elevated alkaline phosphatase above the institution upper limit of normal\n   3. High lactate dehydrogenase (LDH) above the upper limit of normal\n   4. Prior therapy with enzalutamide, abiraterone acetate, or orteronel. Patients are not permitted if they are continuing on the same therapy or restarting a therapy that they have been exposed to in the past.\n   5. Presence of visceral metastasis on imaging\n   6. Presence of clinically significant pain requiring opioid analgesia\n   7. Patients with a Cellsearch CTC > 5 cells per 7.5 mL whole blood (if available as standard of care) are eligible without additional high risk features\n   8. PSA doubling time under 3 months on most recent therapy\n   9. Radiographic progression at entry based on new lesion(s) in bone, soft tissue, or visceral metastases\n7. Age > 18 years.\n8. Ability to understand and the willingness to sign a written informed consent document.\nHealthy volunteers allowed\nMust be MALE\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. History of intercurrent or past medical or psychiatric illness that would make participation in a blood drawing protocol difficult or not feasible at the discretion of the principal investigator or co-investigator(s).\n2. Treatment with an anthracycline or mitoxantrone within 1 week of CTC collection\n3. Prior docetaxel in the castration resistant metastatic setting. Patients treated with docetaxel for metastatic castration sensitive disease will be eligible.\n4. Unwillingness to be followed longitudinally for serial CTC biomarker studies.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Histologically confirmed diagnosis of adenocarcinoma of the prostate. Pure small cell or neuroendocrine tumors of the prostate are not permitted.",
            "criterions": [
                {
                    "exact_snippets": "Histologically confirmed diagnosis of adenocarcinoma of the prostate.",
                    "criterion": "adenocarcinoma of the prostate",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis",
                            "expected_value": "histologically confirmed"
                        }
                    ]
                },
                {
                    "exact_snippets": "Pure small cell or neuroendocrine tumors of the prostate are not permitted.",
                    "criterion": "small cell or neuroendocrine tumors of the prostate",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Clinical or radiographic evidence of metastatic disease.",
            "criterions": [
                {
                    "exact_snippets": "Clinical or radiographic evidence of metastatic disease.",
                    "criterion": "metastatic disease",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": [
                                "clinical",
                                "radiographic"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Planned therapy with either enzalutamide and/or abiraterone acetate within the coming 6 weeks",
            "criterions": [
                {
                    "exact_snippets": "Planned therapy with either enzalutamide",
                    "criterion": "planned therapy",
                    "requirements": [
                        {
                            "requirement_type": "medication",
                            "expected_value": "enzalutamide"
                        }
                    ]
                },
                {
                    "exact_snippets": "Planned therapy with ... abiraterone acetate",
                    "criterion": "planned therapy",
                    "requirements": [
                        {
                            "requirement_type": "medication",
                            "expected_value": "abiraterone acetate"
                        }
                    ]
                },
                {
                    "exact_snippets": "within the coming 6 weeks",
                    "criterion": "planned therapy",
                    "requirements": [
                        {
                            "requirement_type": "timeframe",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Evidence of disease progression on or following most recent therapy as evidenced by at least one of the following:",
            "criterions": [
                {
                    "exact_snippets": "Evidence of disease progression on or following most recent therapy",
                    "criterion": "disease progression",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "on or following most recent therapy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Radiographic evidence of disease progression as defined by one or more new bone scan lesions that is not consistent with flare/healing, or growth of soft tissue/visceral metastases to greater than one centimeter (cm) in longest diameter (2 cm shortest diameter for lymph nodes).",
            "criterions": [
                {
                    "exact_snippets": "Radiographic evidence of disease progression ... one or more new bone scan lesions",
                    "criterion": "disease progression",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": "radiographic"
                        },
                        {
                            "requirement_type": "lesions",
                            "expected_value": "new bone scan lesions"
                        }
                    ]
                },
                {
                    "exact_snippets": "growth of soft tissue/visceral metastases to greater than one centimeter (cm) in longest diameter",
                    "criterion": "soft tissue/visceral metastases",
                    "requirements": [
                        {
                            "requirement_type": "growth",
                            "expected_value": {
                                "operator": ">",
                                "value": 1,
                                "unit": "cm"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "growth of soft tissue/visceral metastases ... (2 cm shortest diameter for lymph nodes)",
                    "criterion": "lymph nodes",
                    "requirements": [
                        {
                            "requirement_type": "growth",
                            "expected_value": {
                                "operator": ">",
                                "value": 2,
                                "unit": "cm"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Clinical progression as defined by the treating physician (such as pain progression)",
            "criterions": [
                {
                    "exact_snippets": "Clinical progression as defined by the treating physician",
                    "criterion": "clinical progression",
                    "requirements": [
                        {
                            "requirement_type": "definition",
                            "expected_value": "as defined by the treating physician"
                        }
                    ]
                },
                {
                    "exact_snippets": "pain progression",
                    "criterion": "pain progression",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Consecutive PSA rises meeting PSA progression criteria as determined by PCWG2 criteria (increase that is >25% and >2 ng/mL above the nadir, and which is confirmed by a second value 3 or more weeks later)",
            "criterions": [
                {
                    "exact_snippets": "Consecutive PSA rises meeting PSA progression criteria as determined by PCWG2 criteria",
                    "criterion": "PSA progression",
                    "requirements": [
                        {
                            "requirement_type": "criteria",
                            "expected_value": "PCWG2"
                        }
                    ]
                },
                {
                    "exact_snippets": "increase that is >25% and >2 ng/mL above the nadir",
                    "criterion": "PSA increase",
                    "requirements": [
                        {
                            "requirement_type": "percentage increase",
                            "expected_value": {
                                "operator": ">",
                                "value": 25,
                                "unit": "%"
                            }
                        },
                        {
                            "requirement_type": "absolute increase",
                            "expected_value": {
                                "operator": ">",
                                "value": 2,
                                "unit": "ng/mL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "confirmed by a second value 3 or more weeks later",
                    "criterion": "PSA confirmation",
                    "requirements": [
                        {
                            "requirement_type": "confirmation time",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. At least two of the following high risk features during screening for rapid disease progression:",
            "criterions": [
                {
                    "exact_snippets": "At least two of the following high risk features during screening for rapid disease progression",
                    "criterion": "high risk features for rapid disease progression",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "features"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Anemia with a hemoglobin <12.0 g/dl",
            "criterions": [
                {
                    "exact_snippets": "Anemia",
                    "criterion": "anemia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "hemoglobin <12.0 g/dl",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 12.0,
                                "unit": "g/dl"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Elevated alkaline phosphatase above the institution upper limit of normal",
            "criterions": [
                {
                    "exact_snippets": "Elevated alkaline phosphatase above the institution upper limit of normal",
                    "criterion": "alkaline phosphatase",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": "above the institution upper limit of normal"
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. High lactate dehydrogenase (LDH) above the upper limit of normal",
            "criterions": [
                {
                    "exact_snippets": "High lactate dehydrogenase (LDH) above the upper limit of normal",
                    "criterion": "lactate dehydrogenase (LDH)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 1,
                                "unit": "upper limit of normal"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Prior therapy with enzalutamide, abiraterone acetate, or orteronel. Patients are not permitted if they are continuing on the same therapy or restarting a therapy that they have been exposed to in the past.",
            "criterions": [
                {
                    "exact_snippets": "Prior therapy with enzalutamide",
                    "criterion": "prior therapy",
                    "requirements": [
                        {
                            "requirement_type": "medication",
                            "expected_value": "enzalutamide"
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior therapy with ... abiraterone acetate",
                    "criterion": "prior therapy",
                    "requirements": [
                        {
                            "requirement_type": "medication",
                            "expected_value": "abiraterone acetate"
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior therapy with ... orteronel",
                    "criterion": "prior therapy",
                    "requirements": [
                        {
                            "requirement_type": "medication",
                            "expected_value": "orteronel"
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients are not permitted if they are continuing on the same therapy",
                    "criterion": "continuation of same therapy",
                    "requirements": [
                        {
                            "requirement_type": "permitted",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients are not permitted if they are ... restarting a therapy that they have been exposed to in the past",
                    "criterion": "restarting past therapy",
                    "requirements": [
                        {
                            "requirement_type": "permitted",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Presence of visceral metastasis on imaging",
            "criterions": [
                {
                    "exact_snippets": "Presence of visceral metastasis on imaging",
                    "criterion": "visceral metastasis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Presence of clinically significant pain requiring opioid analgesia",
            "criterions": [
                {
                    "exact_snippets": "Presence of clinically significant pain",
                    "criterion": "clinically significant pain",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "requiring opioid analgesia",
                    "criterion": "opioid analgesia",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Patients with a Cellsearch CTC > 5 cells per 7.5 mL whole blood (if available as standard of care) are eligible without additional high risk features",
            "criterions": [
                {
                    "exact_snippets": "Cellsearch CTC > 5 cells per 7.5 mL whole blood",
                    "criterion": "Cellsearch CTC",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">",
                                "value": 5,
                                "unit": "cells per 7.5 mL whole blood"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "if available as standard of care",
                    "criterion": "availability of Cellsearch CTC as standard of care",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. PSA doubling time under 3 months on most recent therapy",
            "criterions": [
                {
                    "exact_snippets": "PSA doubling time under 3 months",
                    "criterion": "PSA doubling time",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Radiographic progression at entry based on new lesion(s) in bone, soft tissue, or visceral metastases",
            "criterions": [
                {
                    "exact_snippets": "Radiographic progression at entry based on new lesion(s) in bone",
                    "criterion": "radiographic progression in bone",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Radiographic progression at entry based on new lesion(s) in ... soft tissue",
                    "criterion": "radiographic progression in soft tissue",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Radiographic progression at entry based on new lesion(s) in ... visceral metastases",
                    "criterion": "radiographic progression in visceral metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Age > 18 years.",
            "criterions": [
                {
                    "exact_snippets": "Age > 18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "N/A",
                            "expected_value": {
                                "operator": ">",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Ability to understand and the willingness to sign a written informed consent document.",
            "criterions": [
                {
                    "exact_snippets": "Ability to understand",
                    "criterion": "cognitive ability",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "willingness to sign a written informed consent document",
                    "criterion": "willingness to consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must be MALE",
            "criterions": [
                {
                    "exact_snippets": "MALE",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": "male"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 18 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. History of intercurrent or past medical or psychiatric illness that would make participation in a blood drawing protocol difficult or not feasible at the discretion of the principal investigator or co-investigator(s).",
            "criterions": [
                {
                    "exact_snippets": "History of intercurrent or past medical or psychiatric illness",
                    "criterion": "medical or psychiatric illness",
                    "requirements": [
                        {
                            "requirement_type": "impact on participation",
                            "expected_value": "make participation in a blood drawing protocol difficult or not feasible"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Treatment with an anthracycline or mitoxantrone within 1 week of CTC collection",
            "criterions": [
                {
                    "exact_snippets": "Treatment with an anthracycline or mitoxantrone within 1 week of CTC collection",
                    "criterion": "treatment with anthracycline or mitoxantrone",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "week"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Prior docetaxel in the castration resistant metastatic setting. Patients treated with docetaxel for metastatic castration sensitive disease will be eligible.",
            "criterions": [
                {
                    "exact_snippets": "Prior docetaxel in the castration resistant metastatic setting.",
                    "criterion": "prior docetaxel treatment",
                    "requirements": [
                        {
                            "requirement_type": "setting",
                            "expected_value": "castration resistant metastatic"
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients treated with docetaxel for metastatic castration sensitive disease will be eligible.",
                    "criterion": "docetaxel treatment",
                    "requirements": [
                        {
                            "requirement_type": "setting",
                            "expected_value": "metastatic castration sensitive"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Unwillingness to be followed longitudinally for serial CTC biomarker studies.",
            "criterions": [
                {
                    "exact_snippets": "Unwillingness to be followed longitudinally for serial CTC biomarker studies",
                    "criterion": "willingness to be followed longitudinally for serial CTC biomarker studies",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "4. Castrate levels of testosterone (<50 ng/dl) at most recent assessment and/or documented ongoing Androgen Deprivation Therapy for at lease three months.",
            "criterions": [
                {
                    "exact_snippets": "Castrate levels of testosterone (<50 ng/dl)",
                    "criterion": "testosterone level",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 50,
                                "unit": "ng/dl"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "documented ongoing Androgen Deprivation Therapy for at least three months",
                    "criterion": "Androgen Deprivation Therapy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}