{
    "info": {
        "nct_id": "NCT03093272",
        "official_title": "A Phase 2 Study of Docetaxel Plus Apalutamide in Castration-Resistant Prostate Cancer Patients Post Abiraterone Acetate",
        "inclusion_criteria": "* Histologically confirmed adenocarcinoma of the prostate\n* Castration-resistant prostate cancer requires the following criteria:\n\n  * A castrate level of testosterone (< 50ng/dL)\n  * Prostate cancer progression on or since last treatment as documented by PSA rise or bone progression according to PCWG2 or soft tissue radiographic progression according to RECIST criteria Version 1.1\n  * If on anti-androgen, will need to show no PSA decline after at least a 6 week withdrawal period from the last dose of bicalutamide or nilutamide or 4 weeks from last flutamide dose\n  * Will require a 2 week washout period from last dose of ketoconazole, abiraterone acetate or radiation\n* Treatment with abiraterone acetate for CRPC in the past is required. Does not need to be the last treatment prior to enrollment.\n* There is no limit to number of prior therapies\n* Metastatic disease by bone scan or other nodal or visceral lesions on CT or MRI\n* Age ≥ 18 years\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (See Appendix A)\n* Adequate organ function as evaluated by the following laboratory criteria:\n\n  * Hemoglobin ≥ 9g/dL; no transfusions and erythropoietin supplementation permitted within the last 3 months\n  * Absolute neutrophil count (ANC) ≥ 1500/µL\n  * Platelet count ≥ 100 x 10^9/L\n  * Total bilirubin ≤ upper limit of normal (ULN, Note: In subjects with Gilbert's syndrome, if total bilirubin is ≥ 1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ ULN, subject may be eligible)\n  * AST and ALT < 2.5 x ULN or < 5x the ULN if liver metastasis\n  * Serum creatinine < 2.0 × ULN or creatinine clearance > 30cc/min\n  * Serum albumin ≥ 3.0 g/dL\n  * Serum potassium ≥ 3.5 mmol/L (if < 3.5, can be repleted and reassess for eligibility as long as stable off potassium supplementation for > 48 hrs)\n* Ability to swallow the study drug as a whole tablet\n* The effects of apalutamide and docetaxel on the developing human fetus are unknown. For this reason and because chemotherapeutic agents are known to be teratogenic, men must agree to use adequate contraception. Specifically, they must agree to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. They must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug.\n* 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": "* Pathology consistent with majority of specimen having small cell carcinoma of the prostate (prostate cancer with neuroendocrine features is acceptable).\n* Prior treatment with enzalutamide for CPRC; non-CRPC use allowed (e.g., neoadjuvant, combined with radiation for localized disease and didn't progress while on it in those settings)\n* Prior treatment with docetaxel chemotherapy except if > 12 months since it was given in either the neoadjuvant or adjuvant setting or for hormone sensitive disease (e.g., CHAARTED population)\n* Presence of untreated brain metastasis\n* Seizure or known condition that may pre-dispose to seizure (including but not limited to prior stroke, transient ischemic attack within 1 year prior to randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect). Loss of consciousness within 12 months may be permitted upon discussion with study PI.\n* Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry.\n* Current, recent (within 4 weeks of the first dose of this study), or planned participation in an experimental drug study\n* Persistent grade > 1 (NCI CTCAE v4.0) AEs due to investigational drugs that were administered more than 14 days before study enrollment.\n* Radiation within 2 weeks prior to entering the study\n* Peripheral neuropathy ≥ Grade 2.\n* Current evidence of any of the following:\n\n  * Uncontrolled hypertension\n  * Gastrointestinal disorder affecting absorption\n  * Active infection (e.g., human immunodeficiency virus [HIV] or viral hepatitis) or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated\n* Uncontrolled intercurrent illness including, but not limited to, severe or unstable angina, myocardial infarction, symptomatic congestive heart failure (defined as New York Heart Association Grade II or greater), arterial or venous thromboembolic events (e.g., pulmonary embolism), or clinically significant ventricular arrhythmias, significant vascular disease (e.g. aortic aneurysm, aortic dissection), or symptomatic peripheral vascular disease within 6 months prior to randomization.\n* Psychiatric illness/social situations that would limit compliance with study requirements.\n* Any condition that in the opinion of the investigator, would preclude participation in this study\n* History of allergic reactions or severe hypersensitivity reactions to drugs formulated with polysorbate 80 or antisense oligonucleotides.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to apalutamide or docetaxel\n* Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.\n* Inability to comply with study and/or follow-up procedures",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Histologically confirmed adenocarcinoma of the prostate",
            "criterions": [
                {
                    "exact_snippets": "Histologically confirmed adenocarcinoma of the prostate",
                    "criterion": "adenocarcinoma of the prostate",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": "histologically confirmed"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Castration-resistant prostate cancer requires the following criteria:",
            "criterions": [
                {
                    "exact_snippets": "Castration-resistant prostate cancer",
                    "criterion": "prostate cancer",
                    "requirements": [
                        {
                            "requirement_type": "resistance",
                            "expected_value": "castration-resistant"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* A castrate level of testosterone (< 50ng/dL)",
            "criterions": [
                {
                    "exact_snippets": "A castrate level of testosterone (< 50ng/dL)",
                    "criterion": "testosterone level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 50,
                                        "unit": "ng/dL"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prostate cancer progression on or since last treatment as documented by PSA rise or bone progression according to PCWG2 or soft tissue radiographic progression according to RECIST criteria Version 1.1",
            "criterions": [
                {
                    "exact_snippets": "Prostate cancer progression on or since last treatment",
                    "criterion": "prostate cancer progression",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "on or since last treatment"
                        }
                    ]
                },
                {
                    "exact_snippets": "PSA rise",
                    "criterion": "PSA rise",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "bone progression according to PCWG2",
                    "criterion": "bone progression",
                    "requirements": [
                        {
                            "requirement_type": "standard",
                            "expected_value": "PCWG2"
                        }
                    ]
                },
                {
                    "exact_snippets": "soft tissue radiographic progression according to RECIST criteria Version 1.1",
                    "criterion": "soft tissue radiographic progression",
                    "requirements": [
                        {
                            "requirement_type": "standard",
                            "expected_value": "RECIST criteria Version 1.1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* If on anti-androgen, will need to show no PSA decline after at least a 6 week withdrawal period from the last dose of bicalutamide or nilutamide or 4 weeks from last flutamide dose",
            "criterions": [
                {
                    "exact_snippets": "If on anti-androgen",
                    "criterion": "anti-androgen therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "no PSA decline",
                    "criterion": "PSA decline",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "at least a 6 week withdrawal period from the last dose of bicalutamide or nilutamide",
                    "criterion": "withdrawal period from bicalutamide or nilutamide",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "4 weeks from last flutamide dose",
                    "criterion": "withdrawal period from flutamide",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Will require a 2 week washout period from last dose of ketoconazole, abiraterone acetate or radiation",
            "criterions": [
                {
                    "exact_snippets": "2 week washout period from last dose of ketoconazole",
                    "criterion": "washout period from ketoconazole",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "week"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "2 week washout period from last dose of ... abiraterone acetate",
                    "criterion": "washout period from abiraterone acetate",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "week"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "2 week washout period from last dose of ... radiation",
                    "criterion": "washout period from radiation",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "week"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Treatment with abiraterone acetate for CRPC in the past is required. Does not need to be the last treatment prior to enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Treatment with abiraterone acetate for CRPC in the past is required.",
                    "criterion": "treatment with abiraterone acetate for CRPC",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* There is no limit to number of prior therapies",
            "criterions": [
                {
                    "exact_snippets": "no limit to number of prior therapies",
                    "criterion": "number of prior therapies",
                    "requirements": [
                        {
                            "requirement_type": "limit",
                            "expected_value": "no limit"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Metastatic disease by bone scan or other nodal or visceral lesions on CT or MRI",
            "criterions": [
                {
                    "exact_snippets": "Metastatic disease by bone scan",
                    "criterion": "metastatic disease",
                    "requirements": [
                        {
                            "requirement_type": "detection method",
                            "expected_value": "bone scan"
                        }
                    ]
                },
                {
                    "exact_snippets": "Metastatic disease by ... nodal or visceral lesions on CT or MRI",
                    "criterion": "metastatic disease",
                    "requirements": [
                        {
                            "requirement_type": "detection method",
                            "expected_value": [
                                "CT",
                                "MRI"
                            ]
                        },
                        {
                            "requirement_type": "location",
                            "expected_value": [
                                "nodal",
                                "visceral"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Age ≥ 18 years",
            "criterions": [
                {
                    "exact_snippets": "Age ≥ 18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "N/A",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (See Appendix A)",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "0",
                                "1"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate organ function as evaluated by the following laboratory criteria:",
            "criterions": [
                {
                    "exact_snippets": "Adequate organ function",
                    "criterion": "organ function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hemoglobin ≥ 9g/dL; no transfusions and erythropoietin supplementation permitted within the last 3 months",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin ≥ 9g/dL",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9,
                                "unit": "g/dL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "no transfusions ... within the last 3 months",
                    "criterion": "transfusions",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "erythropoietin supplementation permitted within the last 3 months",
                    "criterion": "erythropoietin supplementation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Absolute neutrophil count (ANC) ≥ 1500/µL",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count (ANC) ≥ 1500/µL",
                    "criterion": "absolute neutrophil count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1500,
                                "unit": "µL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelet count ≥ 100 x 10^9/L",
            "criterions": [
                {
                    "exact_snippets": "Platelet count ≥ 100 x 10^9/L",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100,
                                "unit": "x 10^9/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Total bilirubin ≤ upper limit of normal (ULN, Note: In subjects with Gilbert's syndrome, if total bilirubin is ≥ 1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ ULN, subject may be eligible)",
            "criterions": [
                {
                    "exact_snippets": "Total bilirubin ≤ upper limit of normal (ULN",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "In subjects with Gilbert's syndrome, if total bilirubin is ≥ 1.5 × ULN",
                    "criterion": "total bilirubin in subjects with Gilbert's syndrome",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "measure direct and indirect bilirubin and if direct bilirubin is ≤ ULN",
                    "criterion": "direct bilirubin in subjects with Gilbert's syndrome",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* AST and ALT < 2.5 x ULN or < 5x the ULN if liver metastasis",
            "criterions": [
                {
                    "exact_snippets": "AST and ALT < 2.5 x ULN or < 5x the ULN if liver metastasis",
                    "criterion": "AST",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 2.5,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "AST and ALT < 2.5 x ULN or < 5x the ULN if liver metastasis",
                    "criterion": "ALT",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 2.5,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "AST and ALT < 2.5 x ULN or < 5x the ULN if liver metastasis",
                    "criterion": "AST with liver metastasis",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 5,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "AST and ALT < 2.5 x ULN or < 5x the ULN if liver metastasis",
                    "criterion": "ALT with liver metastasis",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 5,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Serum creatinine < 2.0 × ULN or creatinine clearance > 30cc/min",
            "criterions": [
                {
                    "exact_snippets": "Serum creatinine < 2.0 × ULN",
                    "criterion": "serum creatinine",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 2.0,
                                "unit": "× ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "creatinine clearance > 30cc/min",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "rate",
                            "expected_value": {
                                "operator": ">",
                                "value": 30,
                                "unit": "cc/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Serum albumin ≥ 3.0 g/dL",
            "criterions": [
                {
                    "exact_snippets": "Serum albumin ≥ 3.0 g/dL",
                    "criterion": "serum albumin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3.0,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Serum potassium ≥ 3.5 mmol/L (if < 3.5, can be repleted and reassess for eligibility as long as stable off potassium supplementation for > 48 hrs)",
            "criterions": [
                {
                    "exact_snippets": "Serum potassium ≥ 3.5 mmol/L",
                    "criterion": "serum potassium",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3.5,
                                "unit": "mmol/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "stable off potassium supplementation for > 48 hrs",
                    "criterion": "stability off potassium supplementation",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 48,
                                "unit": "hrs"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Ability to swallow the study drug as a whole tablet",
            "criterions": [
                {
                    "exact_snippets": "Ability to swallow the study drug as a whole tablet",
                    "criterion": "ability to swallow",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "as a whole tablet"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Ability to understand and the willingness to sign a written informed consent document.",
            "criterions": [
                {
                    "exact_snippets": "Ability to understand",
                    "criterion": "cognitive ability",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "willingness to sign a written informed consent document",
                    "criterion": "willingness to consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must 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": "* Pathology consistent with majority of specimen having small cell carcinoma of the prostate (prostate cancer with neuroendocrine features is acceptable).",
            "criterions": [
                {
                    "exact_snippets": "Pathology consistent with majority of specimen having small cell carcinoma of the prostate",
                    "criterion": "small cell carcinoma of the prostate",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "prostate cancer with neuroendocrine features is acceptable",
                    "criterion": "prostate cancer with neuroendocrine features",
                    "requirements": [
                        {
                            "requirement_type": "acceptability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior treatment with enzalutamide for CPRC; non-CRPC use allowed (e.g., neoadjuvant, combined with radiation for localized disease and didn't progress while on it in those settings)",
            "criterions": [
                {
                    "exact_snippets": "Prior treatment with enzalutamide for CPRC",
                    "criterion": "prior treatment with enzalutamide",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "CPRC"
                        }
                    ]
                },
                {
                    "exact_snippets": "non-CRPC use allowed",
                    "criterion": "enzalutamide use",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "non-CRPC"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior treatment with docetaxel chemotherapy except if > 12 months since it was given in either the neoadjuvant or adjuvant setting or for hormone sensitive disease (e.g., CHAARTED population)",
            "criterions": [
                {
                    "exact_snippets": "Prior treatment with docetaxel chemotherapy",
                    "criterion": "prior treatment with docetaxel chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "except if > 12 months since it was given",
                    "criterion": "time since last docetaxel chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "operator": ">",
                                "value": 12,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "in either the neoadjuvant or adjuvant setting",
                    "criterion": "treatment setting",
                    "requirements": [
                        {
                            "requirement_type": "setting",
                            "expected_value": [
                                "neoadjuvant",
                                "adjuvant"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "for hormone sensitive disease (e.g., CHAARTED population)",
                    "criterion": "disease type",
                    "requirements": [
                        {
                            "requirement_type": "sensitivity",
                            "expected_value": "hormone sensitive"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Presence of untreated brain metastasis",
            "criterions": [
                {
                    "exact_snippets": "Presence of untreated brain metastasis",
                    "criterion": "brain metastasis",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "untreated"
                        },
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Seizure or known condition that may pre-dispose to seizure (including but not limited to prior stroke, transient ischemic attack within 1 year prior to randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect). Loss of consciousness within 12 months may be permitted upon discussion with study PI.",
            "criterions": [
                {
                    "exact_snippets": "Seizure",
                    "criterion": "seizure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "known condition that may pre-dispose to seizure",
                    "criterion": "condition pre-disposing to seizure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "prior stroke",
                    "criterion": "prior stroke",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "transient ischemic attack within 1 year prior to randomization",
                    "criterion": "transient ischemic attack",
                    "requirements": [
                        {
                            "requirement_type": "time since occurrence",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "year"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "brain arteriovenous malformation",
                    "criterion": "brain arteriovenous malformation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect",
                    "criterion": "intracranial masses causing edema or mass effect",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Loss of consciousness within 12 months",
                    "criterion": "loss of consciousness",
                    "requirements": [
                        {
                            "requirement_type": "time since occurrence",
                            "expected_value": {
                                "operator": "<=",
                                "value": 12,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry.",
            "criterions": [
                {
                    "exact_snippets": "Medications known to lower the seizure threshold must be discontinued or substituted",
                    "criterion": "medications lowering seizure threshold",
                    "requirements": [
                        {
                            "requirement_type": "discontinuation or substitution",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "at least 4 weeks prior to study entry",
                    "criterion": "time before study entry",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Current, recent (within 4 weeks of the first dose of this study), or planned participation in an experimental drug study",
            "criterions": [
                {
                    "exact_snippets": "Current, recent (within 4 weeks of the first dose of this study), or planned participation in an experimental drug study",
                    "criterion": "participation in an experimental drug study",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "current"
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": "recent (within 4 weeks of the first dose of this study)"
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": "planned"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Persistent grade > 1 (NCI CTCAE v4.0) AEs due to investigational drugs that were administered more than 14 days before study enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Persistent grade > 1 (NCI CTCAE v4.0) AEs",
                    "criterion": "adverse events (AEs)",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">",
                                "value": 1,
                                "unit": "NCI CTCAE v4.0"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "AEs due to investigational drugs that were administered more than 14 days before study enrollment",
                    "criterion": "adverse events (AEs)",
                    "requirements": [
                        {
                            "requirement_type": "cause",
                            "expected_value": "investigational drugs"
                        },
                        {
                            "requirement_type": "time since administration",
                            "expected_value": {
                                "operator": ">",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Radiation within 2 weeks prior to entering the study",
            "criterions": [
                {
                    "exact_snippets": "Radiation within 2 weeks prior to entering the study",
                    "criterion": "radiation",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Peripheral neuropathy ≥ Grade 2.",
            "criterions": [
                {
                    "exact_snippets": "Peripheral neuropathy ≥ Grade 2",
                    "criterion": "peripheral neuropathy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "Grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Current evidence of any of the following:",
            "criterions": [
                {
                    "exact_snippets": "Current evidence of any of the following",
                    "criterion": "evidence of condition",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uncontrolled hypertension",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled hypertension",
                    "criterion": "hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Gastrointestinal disorder affecting absorption",
            "criterions": [
                {
                    "exact_snippets": "Gastrointestinal disorder affecting absorption",
                    "criterion": "gastrointestinal disorder",
                    "requirements": [
                        {
                            "requirement_type": "effect on absorption",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active infection (e.g., human immunodeficiency virus [HIV] or viral hepatitis) or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated",
            "criterions": [
                {
                    "exact_snippets": "Active infection (e.g., human immunodeficiency virus [HIV] or viral hepatitis)",
                    "criterion": "active infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated",
                    "criterion": "medical condition contraindicating corticosteroid use",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uncontrolled intercurrent illness including, but not limited to, severe or unstable angina, myocardial infarction, symptomatic congestive heart failure (defined as New York Heart Association Grade II or greater), arterial or venous thromboembolic events (e.g., pulmonary embolism), or clinically significant ventricular arrhythmias, significant vascular disease (e.g. aortic aneurysm, aortic dissection), or symptomatic peripheral vascular disease within 6 months prior to randomization.",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled intercurrent illness including, but not limited to, severe or unstable angina",
                    "criterion": "angina",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "severe",
                                "unstable"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled intercurrent illness including, but not limited to, ... myocardial infarction",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled intercurrent illness including, but not limited to, ... symptomatic congestive heart failure (defined as New York Heart Association Grade II or greater)",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "New York Heart Association Grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled intercurrent illness including, but not limited to, ... arterial or venous thromboembolic events (e.g., pulmonary embolism)",
                    "criterion": "thromboembolic events",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled intercurrent illness including, but not limited to, ... clinically significant ventricular arrhythmias",
                    "criterion": "ventricular arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "clinical significance",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled intercurrent illness including, but not limited to, ... significant vascular disease (e.g. aortic aneurysm, aortic dissection)",
                    "criterion": "vascular disease",
                    "requirements": [
                        {
                            "requirement_type": "significance",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled intercurrent illness including, but not limited to, ... symptomatic peripheral vascular disease within 6 months prior to randomization",
                    "criterion": "peripheral vascular disease",
                    "requirements": [
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 6 months prior to randomization"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Psychiatric illness/social situations that would limit compliance with study requirements.",
            "criterions": [
                {
                    "exact_snippets": "Psychiatric illness",
                    "criterion": "psychiatric illness",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "social situations that would limit compliance with study requirements",
                    "criterion": "social situations",
                    "requirements": [
                        {
                            "requirement_type": "impact on compliance",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any condition that in the opinion of the investigator, would preclude participation in this study",
            "criterions": [
                {
                    "exact_snippets": "Any condition that in the opinion of the investigator, would preclude participation",
                    "criterion": "condition precluding participation",
                    "requirements": [
                        {
                            "requirement_type": "opinion",
                            "expected_value": "investigator's discretion"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of allergic reactions or severe hypersensitivity reactions to drugs formulated with polysorbate 80 or antisense oligonucleotides.",
            "criterions": [
                {
                    "exact_snippets": "History of allergic reactions or severe hypersensitivity reactions to drugs formulated with polysorbate 80",
                    "criterion": "allergic reactions or severe hypersensitivity reactions to drugs formulated with polysorbate 80",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History of allergic reactions or severe hypersensitivity reactions to ... antisense oligonucleotides",
                    "criterion": "allergic reactions or severe hypersensitivity reactions to antisense oligonucleotides",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of allergic reactions attributed to compounds of similar chemical or biologic composition to apalutamide or docetaxel",
            "criterions": [
                {
                    "exact_snippets": "History of allergic reactions attributed to compounds of similar chemical or biologic composition to apalutamide",
                    "criterion": "allergic reactions to compounds similar to apalutamide",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "History of allergic reactions attributed to compounds of similar chemical or biologic composition to ... docetaxel",
                    "criterion": "allergic reactions to compounds similar to docetaxel",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.",
            "criterions": [
                {
                    "exact_snippets": "Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible.",
                    "criterion": "medications or substances affecting CYP3A4",
                    "requirements": [
                        {
                            "requirement_type": "effect",
                            "expected_value": [
                                "strong inhibitor",
                                "strong inducer"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Inability to comply with study and/or follow-up procedures",
            "criterions": [
                {
                    "exact_snippets": "Inability to comply with study and/or follow-up procedures",
                    "criterion": "compliance with study and follow-up procedures",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "* The effects of apalutamide and docetaxel on the developing human fetus are unknown. For this reason and because chemotherapeutic agents are known to be teratogenic, men must agree to use adequate contraception. Specifically, they must agree to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. They must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug.",
            "criterions": [
                {
                    "exact_snippets": "men must agree to use adequate contraception ... if he is having sex with a woman of childbearing potential",
                    "criterion": "contraception use with women of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "men must agree to use a condom ... if he is having sex with a woman who is pregnant",
                    "criterion": "contraception use with pregnant women",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "They must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug.",
                    "criterion": "sperm donation",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}