{
    "info": {
        "nct_id": "NCT04060394",
        "official_title": "A Phase I/II Dose-Escalation and Efficacy Study of LAE001/Prednisone Plus Afuresertib in Patients With Metastatic Castration-resistant Prostate Cancer Following Standard of Care Treatment",
        "inclusion_criteria": "1. Patients, males ≥18 years of age, must be able to provide written informed consent.\n2. Patients must have documented histological or cytological evidence of adenocarcinoma of the prostate (excluding neuroendocrine differentiation or small cell histology).\n3. Patients must have radiographic evidence of metastatic disease for mCRPC based on the 'Guideline of American Urological Association for Prostate Cancer' before study enrollment. (https://www.auanet.org/guidelines/prostate-cancer-castration-resistant11 guideline)\n4. For PTEN and PIK3CA/AKT status test:\n\n   Phase I: The PTEN/PIK3CA/AKT status test is optional and the result could be either positive, negative, undetermined or invalid. Phase II: Patients will be allowed to enroll regardless of the biomarker status, medical monitor review is necessary before enrollment. The biomarker status tests will be performed with the following order. The biomarker results of all enrolled patients will be used for retrospective analysis purposes.\n   * Patients that have a documentation of \"PTEN LOSS\" and/or PTEN/PIK3CA/AKT alteration from a previous test on either tissue or liquid biopsy (e.g., IHC or next generation sequencing NGS), no further biomarker tests are needed in this study.\n   * Patients who have PTEN or PI3KPIK3CA/AKT alteration status reported other than \"PTEN LOSS\", \"PIK3CA/AKT alterations\" or never completed any PTEN/PIK3CA/AKT test before, could either provide the archival tumor samples collected at any time before study enrollment or do a fresh core tumor biopsy.\n   * As the last option, patients can perform a liquid biopsy for PTEN LOSS and PTEN/PIK3CA/AKT alteration tests by NGS of cfDNA if they have no archival tissue to provide, no tumor lesion for biopsy or a fresh biopsy is not feasible.\n5. Patients must have progressive disease based on the PCWG3 criteria:\n\n   * Patients who progressed based solely on total PSA rising, should have had a sequence of rising values on 3 consecutive occasions of at least 1-week intervals (if the third measurement is not greater than the second measurement, a fourth measurement at least a week apart must be taken and must be greater than the second measurement) and should have 2.0 ng/mL minimum level for entry. Note: Patient must have had a prior PSA response, followed by documented PSA progression on prior hormone treatment.\n   * Patients who have documented disease progression per RECIST 1.1 are eligible independent of PSA.\n   * Patients with bone only progression according to PCWG3 (i.e., bone scan showing\n\n   appearance of ≥2 new lesions).\n6. Patients must have castration levels of testosterone (<50 ng/dL or 1.7 nmol/L). Note: Patients must have undergone androgen deprivation therapy (ADT), such as orchiectomy, or have been on luteinizing hormone releasing hormone (LHRH) agonists or antagonists, for at least 3 months prior to study enrollment. Patients on LHRH agonists/antagonists must remain on these agents for the duration of the study.\n7. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.\n8. Patients must have adequate hematopoietic function by local laboratory within the 28 days before enrollment, as evidenced by:\n\n   * Absolute neutrophil count ≥1,500/μL\n   * Platelet count ≥75,000/μL\n   * Hemoglobin ≥9 g/dL\n9. Note: Criteria must be met without growth factors or transfusion within 10 days prior to the screening lab tests. Total serum bilirubin ≤1.5 × ULN within the 28 days before enrollment (in patients with known Gilbert's syndrome, total bilirubin ≤3 × ULN with direct bilirubin ≤1.5 × ULN).\n10. Aspartate aminotransferase and alanine aminotransferase ≤2.5 × ULN except for patients with tumor involvement of the liver who must have AST and ALT ≤5 × ULN within the 28 days before enrollment.\n11. Patients must have adequate renal function as evidenced by a serum creatinine of\n\n    ≤1.5 × ULN for the reference laboratory or creatinine clearance ≥30 mL/min within the 28 days before enrollment (calculated from Cockcroft-Gault formula or 24-hour urine collection).\n12. Serum potassium ≥3.5 mmol/L and < ULN within the 28 days before enrollment.\n13. Fasting plasma glucose (fasting is defined as no caloric intake for at least 8 hours):\n\n    * ≤126 mg/dL for those patients without a pre-existing diagnosis of Type 1 or Type 2 diabetes mellitus\n    * ≤167 mg/dL for those patients with a pre-existing diagnosis of Type 2 diabetes mellitus AND glycosylated haemoglobin (HbA1C) ≤8%\n14. Phase I: Patients who have mCRPC progressed or are intolerant after receiving at least 1 prior treatments of any anti-androgen (such as abiraterone, enzalutamide, apalutamide, or any other AR antagonists that are approved later), and/or chemotherapy. Patients must have at least 3 weeks of treatment of any antiandrogen and/or completed at least 4 Cycles of docetaxel or cabazitaxel treatment before their screening visit.\n\n    Phase II: Patients who have mCRPC progressed or are intolerant after receiving 1-3 prior standard treatments for mCSPC, or nmCRPC, or mCRPC, including at least one second-generation antiandrogen treatment (i.e., abiraterone, enzalutamide, apalutamide, or darolutamide), and no more than one chemotherapy. Patients must have at least 3 weeks of treatment of any antiandrogen and/or completed at least 3 Cycles of docetaxel or cabazitaxel treatment and/or at least 3 injections of R223 and/or at least 2 injections of sipuleucel-T to be counted as one prior therapy. Patient's current diagnosis at screening must be mCRPC.\n15. Concomitant use of bisphosphonates and other bone supportive agents is allowed if the dose and renal function have been stable for at least 12 weeks before enrollment and no related ≥Grade 2 side effects are present for at least 4 weeks prior to study drug treatment. The minimum washout period is 4 weeks for prostate cancer therapy (cytotoxic, biologics, antiandrogens, etc.) before enrollment, starting from the day the therapies were stopped.\n16. Patients with a female partner of childbearing potential must agree to use condoms plus an additional contraceptive method to avoid conception until the end of relevant systemic exposure plus 90 days following the Clinical Trial Facilitation Group contraception guideline from September 2014.\n17. Patient should be suitable for oral medication and should not have any known gastrointestinal diseases that may interfere with drug absorption.\n18. Life expectancy of at least 6 months.\nHealthy volunteers allowed\nMust be MALE\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Major surgery within 28 days before study treatment and/or have not adequately (Grade 1) recovered from the adverse effects of any major surgical procedures before study treatment.\n2. Patients that received other second-line ADT (including but not limited to ketoconazole and amino glutethimide) within 6 weeks before enrollment.\n3. Patients who have completed sipuleucel-T (Provenge®) treatment within 6 weeks of enrollment.\n4. Patients who have received antiandrogens such as flutamide (EULEXIN®), bicalutamide (CASODEX®), or nilutamide (NILANDRON®) for >3 months must be off treatment for 6 weeks prior to enrollment and should demonstrate a continued rise in PSA after withdrawal.\n5. Patients who have received Radium Ra 223 dichloride (XOFIGO®) must be off therapy for 7 weeks prior to enrollment or Samarium Sm 153 lexidronam (QUADRAMET®) must be off therapy for at least 2 weeks prior to enrollment.\n6. Patients that are currently receiving increasing or chronic treatment (>5 days) with corticosteroids or another immunosuppressive agent, other than the following: daily use of up to 10 mg prednisone (or equivalent) or low-dose steroid for the control of nausea and vomiting, topical steroid, or inhaled steroid use.\n7. Patients who require potassium-wasting diuretics.\n8. Patients who have received any investigational agent beyond those indicated for the treatment of prostate cancer within 5 half-lives of the agent; if the half-life of the agent is not known, the patients must be off investigational therapy for 4 weeks prior to enrollment (whichever is shorter of the two should be preferred).\n9. Patients who have received palliative and other radiotherapy for the target lesion within 4 weeks of study enrollment.\n10. Patients with symptomatic or known central nervous system metastases from prostate cancer or who are at high risk for spinal cord compression, per investigator's judgment.\n11. Patients with a history of hypothalamus, pituitary or adrenal insufficiency.\n12. Patients with >grade 2 neuropathy at study enrollment.\n13. History of another primary malignancy that is currently clinically significant or currently requires active intervention.\n14. Inadequately controlled hypertension (eg, systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥95 mmHg) or hypotension (eg, systolic blood pressure ≤ 80 mmHg or diastolic blood pressure ≤50 mmHg) after up to 3 measurements with at least 5 minutes apart during 28 days before study enrollment.\n15. Patients with active cardiac disease or a history of cardiac dysfunction including any of the following:\n\n    * Severe or unstable angina pectoris or acute coronary syndrome or stroke within 6 months prior to study enrollment.\n    * Symptomatic pericarditis.\n    * Documented myocardial infarction or arterial thrombotic events within 6 months prior to study enrollment.\n    * History of documented congestive heart failure (New York Health Association functional classification III to IV).\n    * Documented history of cardiomyopathy.\n    * Known left ventricular ejection fraction <50% as determined by multiple gated acquisition scan or echocardiogram within 28 days prior to enrollment.\n    * History of clinically significant cardiac arrhythmias unsuitable to participate, as determined by the investigator.\n16. Patients with a Fridericia-corrected QT (QTcF) interval of >470 msec on the screening ECG (using the QTcF formula), has a short/long QT syndrome, or history of QT prolongation/Torsades de Pointes, unless prolonged QTc interval is due to (right or left) bundle branch block and/or pacemaker rhythm. If wide QRS complex is present, cardiology consultation is required to assess the risk for Torsade de Pointes.\n17. Patients with a history of an active infection (viral, bacterial, or fungal) requiring systemic therapy within 10 days before enrollment, including but not limited to tuberculosis.\n18. Patients who have active human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infections.\n19. Patients that are currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzyme CYP1A (including but not limited:\n\n    α-Naphthoflavone, Furafylline, Omeprazole, Lansoprazole) and isoenzyme CYP3A (including but not limited: Itraconazole, Ketoconazole, Azamulin, Troleandomycin, Verapamil, Rifampicin). The patients must have discontinued moderate or strong inducers for at least 2 weeks prior to study enrollment and must have discontinued moderate or strong inhibitors for at least 1 week before study enrollment. Spironolactone Strong bile salt export pump (BSEP) inhibitors, grapefruit juice, herbal medicines such as St. John's wort, Kava, ephedra, gingko biloba, dehydroepiandrosterone, yohimbe, saw palmetto and ginseng should be discontinued.\n20. Sexually active males not willing to use a condom during the whole course of the study and for 16 weeks after stopping treatment. Male patients must not father a child in this period. A condom is required to be used also by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the drug via seminal fluid.\n21. Patients with any other medical, psychiatric, or social condition, including substance abuse, which in the opinion of the investigator, would preclude participation in the study.\n22. Patients with a history of upper gastrointestinal bleeding or uncontrolled peptic disease in the previous 3 months which in Investigator's opinion may impact patient's participation in the study.\n23. Patients have previously received AKT or PI3 kinase pathway or mTOR inhibitors",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Patients, males ≥18 years of age, must be able to provide written informed consent.",
            "criterions": [
                {
                    "exact_snippets": "males",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": "male"
                        }
                    ]
                },
                {
                    "exact_snippets": "≥18 years of age",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "must be able to provide written informed consent",
                    "criterion": "ability to provide consent",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Patients must have documented histological or cytological evidence of adenocarcinoma of the prostate (excluding neuroendocrine differentiation or small cell histology).",
            "criterions": [
                {
                    "exact_snippets": "documented histological or cytological evidence of adenocarcinoma of the prostate",
                    "criterion": "adenocarcinoma of the prostate",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": "documented histological or cytological"
                        }
                    ]
                },
                {
                    "exact_snippets": "excluding neuroendocrine differentiation or small cell histology",
                    "criterion": "adenocarcinoma of the prostate",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": [
                                "neuroendocrine differentiation",
                                "small cell histology"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patients must have radiographic evidence of metastatic disease for mCRPC based on the 'Guideline of American Urological Association for Prostate Cancer' before study enrollment. (https://www.auanet.org/guidelines/prostate-cancer-castration-resistant11 guideline)",
            "criterions": [
                {
                    "exact_snippets": "radiographic evidence of metastatic disease",
                    "criterion": "metastatic disease",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": "radiographic"
                        }
                    ]
                },
                {
                    "exact_snippets": "mCRPC",
                    "criterion": "mCRPC",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "based on the 'Guideline of American Urological Association for Prostate Cancer'",
                    "criterion": "guideline adherence",
                    "requirements": [
                        {
                            "requirement_type": "source",
                            "expected_value": "Guideline of American Urological Association for Prostate Cancer"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. For PTEN and PIK3CA/AKT status test:",
            "criterions": [
                {
                    "exact_snippets": "PTEN ... status test",
                    "criterion": "PTEN status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "PIK3CA/AKT status test",
                    "criterion": "PIK3CA/AKT status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Phase I: The PTEN/PIK3CA/AKT status test is optional and the result could be either positive, negative, undetermined or invalid. Phase II: Patients will be allowed to enroll regardless of the biomarker status, medical monitor review is necessary before enrollment. The biomarker status tests will be performed with the following order. The biomarker results of all enrolled patients will be used for retrospective analysis purposes.",
            "criterions": [
                {
                    "exact_snippets": "PTEN/PIK3CA/AKT status test is optional",
                    "criterion": "PTEN/PIK3CA/AKT status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "result could be either positive, negative, undetermined or invalid",
                    "criterion": "PTEN/PIK3CA/AKT status",
                    "requirements": [
                        {
                            "requirement_type": "possible results",
                            "expected_value": [
                                "positive",
                                "negative",
                                "undetermined",
                                "invalid"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "biomarker status, medical monitor review is necessary before enrollment",
                    "criterion": "medical monitor review",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients that have a documentation of \"PTEN LOSS\" and/or PTEN/PIK3CA/AKT alteration from a previous test on either tissue or liquid biopsy (e.g., IHC or next generation sequencing NGS), no further biomarker tests are needed in this study.",
            "criterions": [
                {
                    "exact_snippets": "documentation of \"PTEN LOSS\"",
                    "criterion": "PTEN loss",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "PTEN/PIK3CA/AKT alteration",
                    "criterion": "PTEN/PIK3CA/AKT alteration",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "previous test on either tissue or liquid biopsy",
                    "criterion": "previous test",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "tissue biopsy",
                                "liquid biopsy"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "IHC or next generation sequencing NGS",
                    "criterion": "test method",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "IHC",
                                "next generation sequencing NGS"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have PTEN or PI3KPIK3CA/AKT alteration status reported other than \"PTEN LOSS\", \"PIK3CA/AKT alterations\" or never completed any PTEN/PIK3CA/AKT test before, could either provide the archival tumor samples collected at any time before study enrollment or do a fresh core tumor biopsy.",
            "criterions": [
                {
                    "exact_snippets": "PTEN or PI3KPIK3CA/AKT alteration status reported other than \"PTEN LOSS\", \"PIK3CA/AKT alterations\"",
                    "criterion": "PTEN or PI3KPIK3CA/AKT alteration status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "other than \"PTEN LOSS\"",
                                "other than \"PIK3CA/AKT alterations\""
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "never completed any PTEN/PIK3CA/AKT test before",
                    "criterion": "PTEN/PIK3CA/AKT test completion",
                    "requirements": [
                        {
                            "requirement_type": "completion",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "could either provide the archival tumor samples collected at any time before study enrollment",
                    "criterion": "archival tumor samples",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "do a fresh core tumor biopsy",
                    "criterion": "fresh core tumor biopsy",
                    "requirements": [
                        {
                            "requirement_type": "completion",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* As the last option, patients can perform a liquid biopsy for PTEN LOSS and PTEN/PIK3CA/AKT alteration tests by NGS of cfDNA if they have no archival tissue to provide, no tumor lesion for biopsy or a fresh biopsy is not feasible.",
            "criterions": [
                {
                    "exact_snippets": "liquid biopsy for PTEN LOSS",
                    "criterion": "PTEN LOSS",
                    "requirements": [
                        {
                            "requirement_type": "test",
                            "expected_value": "liquid biopsy"
                        }
                    ]
                },
                {
                    "exact_snippets": "PTEN/PIK3CA/AKT alteration tests by NGS of cfDNA",
                    "criterion": "PTEN/PIK3CA/AKT alteration",
                    "requirements": [
                        {
                            "requirement_type": "test",
                            "expected_value": "NGS of cfDNA"
                        }
                    ]
                },
                {
                    "exact_snippets": "if they have no archival tissue to provide",
                    "criterion": "archival tissue",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "no tumor lesion for biopsy",
                    "criterion": "tumor lesion for biopsy",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "a fresh biopsy is not feasible",
                    "criterion": "fresh biopsy",
                    "requirements": [
                        {
                            "requirement_type": "feasibility",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Patients must have progressive disease based on the PCWG3 criteria:",
            "criterions": [
                {
                    "exact_snippets": "progressive disease based on the PCWG3 criteria",
                    "criterion": "progressive disease",
                    "requirements": [
                        {
                            "requirement_type": "criteria",
                            "expected_value": "PCWG3"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who progressed based solely on total PSA rising, should have had a sequence of rising values on 3 consecutive occasions of at least 1-week intervals (if the third measurement is not greater than the second measurement, a fourth measurement at least a week apart must be taken and must be greater than the second measurement) and should have 2.0 ng/mL minimum level for entry. Note: Patient must have had a prior PSA response, followed by documented PSA progression on prior hormone treatment.",
            "criterions": [
                {
                    "exact_snippets": "progressed based solely on total PSA rising",
                    "criterion": "PSA progression",
                    "requirements": [
                        {
                            "requirement_type": "cause",
                            "expected_value": "total PSA rising"
                        }
                    ]
                },
                {
                    "exact_snippets": "sequence of rising values on 3 consecutive occasions of at least 1-week intervals",
                    "criterion": "PSA rising sequence",
                    "requirements": [
                        {
                            "requirement_type": "pattern",
                            "expected_value": "3 consecutive occasions of rising values"
                        },
                        {
                            "requirement_type": "interval",
                            "expected_value": "at least 1-week intervals"
                        }
                    ]
                },
                {
                    "exact_snippets": "if the third measurement is not greater than the second measurement, a fourth measurement at least a week apart must be taken and must be greater than the second measurement",
                    "criterion": "PSA measurement sequence",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "third measurement not greater than second"
                        },
                        {
                            "requirement_type": "additional measurement",
                            "expected_value": "fourth measurement at least a week apart and greater than second"
                        }
                    ]
                },
                {
                    "exact_snippets": "2.0 ng/mL minimum level for entry",
                    "criterion": "PSA level",
                    "requirements": [
                        {
                            "requirement_type": "minimum level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2.0,
                                "unit": "ng/mL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Patient must have had a prior PSA response",
                    "criterion": "prior PSA response",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "documented PSA progression on prior hormone treatment",
                    "criterion": "PSA progression on hormone treatment",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have documented disease progression per RECIST 1.1 are eligible independent of PSA.",
            "criterions": [
                {
                    "exact_snippets": "documented disease progression per RECIST 1.1",
                    "criterion": "disease progression",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "standard",
                            "expected_value": "RECIST 1.1"
                        }
                    ]
                },
                {
                    "exact_snippets": "independent of PSA",
                    "criterion": "PSA dependency",
                    "requirements": [
                        {
                            "requirement_type": "dependency",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with bone only progression according to PCWG3 (i.e., bone scan showing",
            "criterions": [
                {
                    "exact_snippets": "bone only progression according to PCWG3",
                    "criterion": "bone only progression",
                    "requirements": [
                        {
                            "requirement_type": "standard",
                            "expected_value": "PCWG3"
                        }
                    ]
                }
            ]
        },
        {
            "line": "appearance of ≥2 new lesions).",
            "criterions": [
                {
                    "exact_snippets": "appearance of ≥2 new lesions",
                    "criterion": "new lesions",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Patients must have castration levels of testosterone (<50 ng/dL or 1.7 nmol/L). Note: Patients must have undergone androgen deprivation therapy (ADT), such as orchiectomy, or have been on luteinizing hormone releasing hormone (LHRH) agonists or antagonists, for at least 3 months prior to study enrollment. Patients on LHRH agonists/antagonists must remain on these agents for the duration of the study.",
            "criterions": [
                {
                    "exact_snippets": "castration levels of testosterone (<50 ng/dL or 1.7 nmol/L)",
                    "criterion": "testosterone levels",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 50,
                                        "unit": "ng/dL"
                                    },
                                    {
                                        "operator": "<",
                                        "value": 1.7,
                                        "unit": "nmol/L"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "undergone androgen deprivation therapy (ADT), such as orchiectomy, or have been on luteinizing hormone releasing hormone (LHRH) agonists or antagonists, for at least 3 months prior to study enrollment",
                    "criterion": "androgen deprivation therapy (ADT)",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 3,
                                        "unit": "months"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients on LHRH agonists/antagonists must remain on these agents for the duration of the study",
                    "criterion": "LHRH agonists/antagonists",
                    "requirements": [
                        {
                            "requirement_type": "continuation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Patients must have adequate hematopoietic function by local laboratory within the 28 days before enrollment, as evidenced by:",
            "criterions": [
                {
                    "exact_snippets": "adequate hematopoietic function",
                    "criterion": "hematopoietic function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Absolute neutrophil count ≥1,500/μL",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count ≥1,500/μL",
                    "criterion": "absolute neutrophil count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1500,
                                "unit": "μL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelet count ≥75,000/μL",
            "criterions": [
                {
                    "exact_snippets": "Platelet count ≥75,000/μL",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 75000,
                                "unit": "μL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hemoglobin ≥9 g/dL",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin ≥9 g/dL",
                    "criterion": "hemoglobin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Note: Criteria must be met without growth factors or transfusion within 10 days prior to the screening lab tests. Total serum bilirubin ≤1.5 × ULN within the 28 days before enrollment (in patients with known Gilbert's syndrome, total bilirubin ≤3 × ULN with direct bilirubin ≤1.5 × ULN).",
            "criterions": [
                {
                    "exact_snippets": "Total serum bilirubin ≤1.5 × ULN within the 28 days before enrollment",
                    "criterion": "total serum bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "in patients with known Gilbert's syndrome, total bilirubin ≤3 × ULN",
                    "criterion": "total bilirubin in patients with known Gilbert's syndrome",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "in patients with known Gilbert's syndrome, ... direct bilirubin ≤1.5 × ULN",
                    "criterion": "direct bilirubin in patients with known Gilbert's syndrome",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Aspartate aminotransferase and alanine aminotransferase ≤2.5 × ULN except for patients with tumor involvement of the liver who must have AST and ALT ≤5 × ULN within the 28 days before enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Aspartate aminotransferase ... ≤2.5 × ULN",
                    "criterion": "aspartate aminotransferase",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "× ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alanine aminotransferase ≤2.5 × ULN",
                    "criterion": "alanine aminotransferase",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "× ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "patients with tumor involvement of the liver ... AST and ALT ≤5 × ULN",
                    "criterion": "aspartate aminotransferase",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 5,
                                "unit": "× ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "patients with tumor involvement of the liver ... AST and ALT ≤5 × ULN",
                    "criterion": "alanine aminotransferase",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 5,
                                "unit": "× ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "within the 28 days before enrollment",
                    "criterion": "timeframe before enrollment",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "28 days"
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Patients must have adequate renal function as evidenced by a serum creatinine of",
            "criterions": [
                {
                    "exact_snippets": "adequate renal function as evidenced by a serum creatinine",
                    "criterion": "renal function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": "evidenced by a serum creatinine"
                        }
                    ]
                }
            ]
        },
        {
            "line": "≤1.5 × ULN for the reference laboratory or creatinine clearance ≥30 mL/min within the 28 days before enrollment (calculated from Cockcroft-Gault formula or 24-hour urine collection).",
            "criterions": [
                {
                    "exact_snippets": "≤1.5 × ULN for the reference laboratory",
                    "criterion": "creatinine level",
                    "requirements": [
                        {
                            "requirement_type": "comparison",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "× ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "creatinine clearance ≥30 mL/min within the 28 days before enrollment",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "comparison",
                            "expected_value": {
                                "operator": ">=",
                                "value": 30,
                                "unit": "mL/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Serum potassium ≥3.5 mmol/L and < ULN within the 28 days before enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Serum potassium ≥3.5 mmol/L and < ULN within the 28 days before enrollment.",
                    "criterion": "serum potassium",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 3.5,
                                        "unit": "mmol/L"
                                    },
                                    {
                                        "operator": "<",
                                        "value": 1,
                                        "unit": "ULN"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Fasting plasma glucose (fasting is defined as no caloric intake for at least 8 hours):",
            "criterions": [
                {
                    "exact_snippets": "Fasting plasma glucose",
                    "criterion": "fasting plasma glucose",
                    "requirements": [
                        {
                            "requirement_type": "fasting duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 8,
                                "unit": "hours"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* ≤126 mg/dL for those patients without a pre-existing diagnosis of Type 1 or Type 2 diabetes mellitus",
            "criterions": [
                {
                    "exact_snippets": "≤126 mg/dL for those patients without a pre-existing diagnosis of Type 1 or Type 2 diabetes mellitus",
                    "criterion": "blood glucose level",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 126,
                                "unit": "mg/dL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "pre-existing diagnosis of Type 1 or Type 2 diabetes mellitus",
                    "criterion": "pre-existing diagnosis of diabetes mellitus",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* ≤167 mg/dL for those patients with a pre-existing diagnosis of Type 2 diabetes mellitus AND glycosylated haemoglobin (HbA1C) ≤8%",
            "criterions": [
                {
                    "exact_snippets": "pre-existing diagnosis of Type 2 diabetes mellitus",
                    "criterion": "Type 2 diabetes mellitus",
                    "requirements": [
                        {
                            "requirement_type": "pre-existing diagnosis",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "glycosylated haemoglobin (HbA1C) ≤8%",
                    "criterion": "glycosylated haemoglobin (HbA1C)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 8,
                                "unit": "%"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "≤167 mg/dL",
                    "criterion": "blood glucose level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 167,
                                "unit": "mg/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Phase I: Patients who have mCRPC progressed or are intolerant after receiving at least 1 prior treatments of any anti-androgen (such as abiraterone, enzalutamide, apalutamide, or any other AR antagonists that are approved later), and/or chemotherapy. Patients must have at least 3 weeks of treatment of any antiandrogen and/or completed at least 4 Cycles of docetaxel or cabazitaxel treatment before their screening visit.",
            "criterions": [
                {
                    "exact_snippets": "mCRPC progressed or are intolerant",
                    "criterion": "mCRPC progression or intolerance",
                    "requirements": [
                        {
                            "requirement_type": "progression or intolerance",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "at least 1 prior treatments of any anti-androgen",
                    "criterion": "prior anti-androgen treatment",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "treatment"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "at least 3 weeks of treatment of any antiandrogen",
                    "criterion": "duration of antiandrogen treatment",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "completed at least 4 Cycles of docetaxel or cabazitaxel treatment",
                    "criterion": "cycles of docetaxel or cabazitaxel treatment",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "cycles"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Phase II: Patients who have mCRPC progressed or are intolerant after receiving 1-3 prior standard treatments for mCSPC, or nmCRPC, or mCRPC, including at least one second-generation antiandrogen treatment (i.e., abiraterone, enzalutamide, apalutamide, or darolutamide), and no more than one chemotherapy. Patients must have at least 3 weeks of treatment of any antiandrogen and/or completed at least 3 Cycles of docetaxel or cabazitaxel treatment and/or at least 3 injections of R223 and/or at least 2 injections of sipuleucel-T to be counted as one prior therapy. Patient's current diagnosis at screening must be mCRPC.",
            "criterions": [
                {
                    "exact_snippets": "mCRPC progressed or are intolerant after receiving 1-3 prior standard treatments",
                    "criterion": "mCRPC progression or intolerance",
                    "requirements": [
                        {
                            "requirement_type": "progression or intolerance",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "1-3 prior standard treatments for mCSPC, or nmCRPC, or mCRPC",
                    "criterion": "prior standard treatments",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 1,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "including at least one second-generation antiandrogen treatment (i.e., abiraterone, enzalutamide, apalutamide, or darolutamide)",
                    "criterion": "second-generation antiandrogen treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "no more than one chemotherapy",
                    "criterion": "chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 1,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "at least 3 weeks of treatment of any antiandrogen",
                    "criterion": "antiandrogen treatment duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 3,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "completed at least 3 Cycles of docetaxel or cabazitaxel treatment",
                    "criterion": "docetaxel or cabazitaxel treatment cycles",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 3,
                                        "unit": "cycles"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "at least 3 injections of R223",
                    "criterion": "R223 injections",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 3,
                                        "unit": "injections"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "at least 2 injections of sipuleucel-T",
                    "criterion": "sipuleucel-T injections",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 2,
                                        "unit": "injections"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Patient's current diagnosis at screening must be mCRPC",
                    "criterion": "current diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis",
                            "expected_value": "mCRPC"
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Concomitant use of bisphosphonates and other bone supportive agents is allowed if the dose and renal function have been stable for at least 12 weeks before enrollment and no related ≥Grade 2 side effects are present for at least 4 weeks prior to study drug treatment. The minimum washout period is 4 weeks for prostate cancer therapy (cytotoxic, biologics, antiandrogens, etc.) before enrollment, starting from the day the therapies were stopped.",
            "criterions": [
                {
                    "exact_snippets": "Concomitant use of bisphosphonates and other bone supportive agents is allowed",
                    "criterion": "concomitant use of bisphosphonates and other bone supportive agents",
                    "requirements": [
                        {
                            "requirement_type": "allowance",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "dose and renal function have been stable for at least 12 weeks before enrollment",
                    "criterion": "dose stability",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "dose and renal function have been stable for at least 12 weeks before enrollment",
                    "criterion": "renal function stability",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "no related ≥Grade 2 side effects are present for at least 4 weeks prior to study drug treatment",
                    "criterion": "related side effects",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<",
                                "value": 2,
                                "unit": "Grade"
                            }
                        },
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "The minimum washout period is 4 weeks for prostate cancer therapy (cytotoxic, biologics, antiandrogens, etc.) before enrollment",
                    "criterion": "washout period for prostate cancer therapy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "16. Patients with a female partner of childbearing potential must agree to use condoms plus an additional contraceptive method to avoid conception until the end of relevant systemic exposure plus 90 days following the Clinical Trial Facilitation Group contraception guideline from September 2014.",
            "criterions": [
                {
                    "exact_snippets": "Patients with a female partner of childbearing potential",
                    "criterion": "female partner of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must agree to use condoms plus an additional contraceptive method",
                    "criterion": "contraceptive method",
                    "requirements": [
                        {
                            "requirement_type": "agreement to use",
                            "expected_value": [
                                "condoms",
                                "additional contraceptive method"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "until the end of relevant systemic exposure plus 90 days",
                    "criterion": "duration of contraceptive use",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "until the end of relevant systemic exposure plus 90 days"
                        }
                    ]
                }
            ]
        },
        {
            "line": "17. Patient should be suitable for oral medication and should not have any known gastrointestinal diseases that may interfere with drug absorption.",
            "criterions": [
                {
                    "exact_snippets": "suitable for oral medication",
                    "criterion": "suitability for oral medication",
                    "requirements": [
                        {
                            "requirement_type": "suitability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "should not have any known gastrointestinal diseases",
                    "criterion": "gastrointestinal diseases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "that may interfere with drug absorption",
                    "criterion": "interference with drug absorption",
                    "requirements": [
                        {
                            "requirement_type": "interference",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "18. Life expectancy of at least 6 months.",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy of at least 6 months.",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "healthy volunteers",
                    "requirements": [
                        {
                            "requirement_type": "participation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must be MALE",
            "criterions": [
                {
                    "exact_snippets": "Must be 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. Major surgery within 28 days before study treatment and/or have not adequately (Grade 1) recovered from the adverse effects of any major surgical procedures before study treatment.",
            "criterions": [
                {
                    "exact_snippets": "Major surgery within 28 days before study treatment",
                    "criterion": "major surgery",
                    "requirements": [
                        {
                            "requirement_type": "time since surgery",
                            "expected_value": {
                                "operator": "<",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "have not adequately (Grade 1) recovered from the adverse effects of any major surgical procedures before study treatment",
                    "criterion": "recovery from adverse effects of major surgery",
                    "requirements": [
                        {
                            "requirement_type": "recovery grade",
                            "expected_value": "Grade 1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Patients that received other second-line ADT (including but not limited to ketoconazole and amino glutethimide) within 6 weeks before enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Patients that received other second-line ADT (including but not limited to ketoconazole and amino glutethimide) within 6 weeks before enrollment.",
                    "criterion": "second-line ADT",
                    "requirements": [
                        {
                            "requirement_type": "receipt",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patients who have completed sipuleucel-T (Provenge®) treatment within 6 weeks of enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Patients who have completed sipuleucel-T (Provenge®) treatment within 6 weeks of enrollment.",
                    "criterion": "sipuleucel-T (Provenge®) treatment",
                    "requirements": [
                        {
                            "requirement_type": "completion",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time since completion",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Patients who have received antiandrogens such as flutamide (EULEXIN®), bicalutamide (CASODEX®), or nilutamide (NILANDRON®) for >3 months must be off treatment for 6 weeks prior to enrollment and should demonstrate a continued rise in PSA after withdrawal.",
            "criterions": [
                {
                    "exact_snippets": "Patients who have received antiandrogens such as flutamide (EULEXIN®), bicalutamide (CASODEX®), or nilutamide (NILANDRON®)",
                    "criterion": "antiandrogen treatment",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "must be off treatment for 6 weeks prior to enrollment",
                    "criterion": "off antiandrogen treatment",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "should demonstrate a continued rise in PSA after withdrawal",
                    "criterion": "PSA level",
                    "requirements": [
                        {
                            "requirement_type": "trend",
                            "expected_value": "continued rise after withdrawal"
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Patients who have received Radium Ra 223 dichloride (XOFIGO®) must be off therapy for 7 weeks prior to enrollment or Samarium Sm 153 lexidronam (QUADRAMET®) must be off therapy for at least 2 weeks prior to enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Patients who have received Radium Ra 223 dichloride (XOFIGO®) must be off therapy for 7 weeks prior to enrollment",
                    "criterion": "Radium Ra 223 dichloride (XOFIGO®) therapy",
                    "requirements": [
                        {
                            "requirement_type": "off therapy duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 7,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Samarium Sm 153 lexidronam (QUADRAMET®) must be off therapy for at least 2 weeks prior to enrollment",
                    "criterion": "Samarium Sm 153 lexidronam (QUADRAMET®) therapy",
                    "requirements": [
                        {
                            "requirement_type": "off therapy duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Patients that are currently receiving increasing or chronic treatment (>5 days) with corticosteroids or another immunosuppressive agent, other than the following: daily use of up to 10 mg prednisone (or equivalent) or low-dose steroid for the control of nausea and vomiting, topical steroid, or inhaled steroid use.",
            "criterions": [
                {
                    "exact_snippets": "Patients that are currently receiving increasing or chronic treatment (>5 days) with corticosteroids or another immunosuppressive agent",
                    "criterion": "corticosteroids or another immunosuppressive agent treatment",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 5,
                                "unit": "days"
                            }
                        },
                        {
                            "requirement_type": "status",
                            "expected_value": "increasing or chronic"
                        }
                    ]
                },
                {
                    "exact_snippets": "daily use of up to 10 mg prednisone (or equivalent)",
                    "criterion": "prednisone (or equivalent) use",
                    "requirements": [
                        {
                            "requirement_type": "dosage",
                            "expected_value": {
                                "operator": "<=",
                                "value": 10,
                                "unit": "mg"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "low-dose steroid for the control of nausea and vomiting",
                    "criterion": "low-dose steroid use for nausea and vomiting",
                    "requirements": [
                        {
                            "requirement_type": "purpose",
                            "expected_value": "control of nausea and vomiting"
                        }
                    ]
                },
                {
                    "exact_snippets": "topical steroid",
                    "criterion": "topical steroid use",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "inhaled steroid use",
                    "criterion": "inhaled steroid use",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Patients who require potassium-wasting diuretics.",
            "criterions": [
                {
                    "exact_snippets": "Patients who require potassium-wasting diuretics",
                    "criterion": "potassium-wasting diuretics",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Patients who have received any investigational agent beyond those indicated for the treatment of prostate cancer within 5 half-lives of the agent; if the half-life of the agent is not known, the patients must be off investigational therapy for 4 weeks prior to enrollment (whichever is shorter of the two should be preferred).",
            "criterions": [
                {
                    "exact_snippets": "Patients who have received any investigational agent beyond those indicated for the treatment of prostate cancer",
                    "criterion": "investigational agent use",
                    "requirements": [
                        {
                            "requirement_type": "indication",
                            "expected_value": "beyond those indicated for the treatment of prostate cancer"
                        }
                    ]
                },
                {
                    "exact_snippets": "within 5 half-lives of the agent",
                    "criterion": "time since last investigational agent",
                    "requirements": [
                        {
                            "requirement_type": "time since last dose",
                            "expected_value": {
                                "operator": "<=",
                                "value": 5,
                                "unit": "half-lives"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "if the half-life of the agent is not known, the patients must be off investigational therapy for 4 weeks prior to enrollment",
                    "criterion": "time since last investigational agent",
                    "requirements": [
                        {
                            "requirement_type": "time since last dose",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Patients who have received palliative and other radiotherapy for the target lesion within 4 weeks of study enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Patients who have received palliative and other radiotherapy",
                    "criterion": "radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "palliative",
                                "other"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "target lesion",
                    "criterion": "target lesion",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "radiotherapy"
                        }
                    ]
                },
                {
                    "exact_snippets": "within 4 weeks of study enrollment",
                    "criterion": "time since radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Patients with a history of hypothalamus, pituitary or adrenal insufficiency.",
            "criterions": [
                {
                    "exact_snippets": "history of hypothalamus ... insufficiency",
                    "criterion": "hypothalamus insufficiency",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of ... pituitary ... insufficiency",
                    "criterion": "pituitary insufficiency",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of ... adrenal insufficiency",
                    "criterion": "adrenal insufficiency",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Patients with >grade 2 neuropathy at study enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Patients with >grade 2 neuropathy",
                    "criterion": "neuropathy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">",
                                "value": 2,
                                "unit": "grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. History of another primary malignancy that is currently clinically significant or currently requires active intervention.",
            "criterions": [
                {
                    "exact_snippets": "History of another primary malignancy",
                    "criterion": "another primary malignancy",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "currently clinically significant",
                    "criterion": "clinical significance of another primary malignancy",
                    "requirements": [
                        {
                            "requirement_type": "clinical significance",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "currently requires active intervention",
                    "criterion": "active intervention for another primary malignancy",
                    "requirements": [
                        {
                            "requirement_type": "active intervention",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Inadequately controlled hypertension (eg, systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥95 mmHg) or hypotension (eg, systolic blood pressure ≤ 80 mmHg or diastolic blood pressure ≤50 mmHg) after up to 3 measurements with at least 5 minutes apart during 28 days before study enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Inadequately controlled hypertension (eg, systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥95 mmHg)",
                    "criterion": "hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "systolic blood pressure",
                            "expected_value": {
                                "operator": ">=",
                                "value": 160,
                                "unit": "mmHg"
                            }
                        },
                        {
                            "requirement_type": "diastolic blood pressure",
                            "expected_value": {
                                "operator": ">=",
                                "value": 95,
                                "unit": "mmHg"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "hypotension (eg, systolic blood pressure ≤ 80 mmHg or diastolic blood pressure ≤50 mmHg)",
                    "criterion": "hypotension",
                    "requirements": [
                        {
                            "requirement_type": "systolic blood pressure",
                            "expected_value": {
                                "operator": "<=",
                                "value": 80,
                                "unit": "mmHg"
                            }
                        },
                        {
                            "requirement_type": "diastolic blood pressure",
                            "expected_value": {
                                "operator": "<=",
                                "value": 50,
                                "unit": "mmHg"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "after up to 3 measurements with at least 5 minutes apart during 28 days before study enrollment",
                    "criterion": "blood pressure measurement protocol",
                    "requirements": [
                        {
                            "requirement_type": "number of measurements",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "measurements"
                            }
                        },
                        {
                            "requirement_type": "time between measurements",
                            "expected_value": {
                                "operator": ">=",
                                "value": 5,
                                "unit": "minutes"
                            }
                        },
                        {
                            "requirement_type": "time frame before enrollment",
                            "expected_value": {
                                "operator": "=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Patients with active cardiac disease or a history of cardiac dysfunction including any of the following:",
            "criterions": [
                {
                    "exact_snippets": "active cardiac disease",
                    "criterion": "cardiac disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of cardiac dysfunction",
                    "criterion": "cardiac dysfunction",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Severe or unstable angina pectoris or acute coronary syndrome or stroke within 6 months prior to study enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Severe or unstable angina pectoris",
                    "criterion": "angina pectoris",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "severe",
                                "unstable"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "acute coronary syndrome",
                    "criterion": "coronary syndrome",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "acute"
                        }
                    ]
                },
                {
                    "exact_snippets": "stroke within 6 months prior to study enrollment",
                    "criterion": "stroke",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Symptomatic pericarditis.",
            "criterions": [
                {
                    "exact_snippets": "Symptomatic pericarditis",
                    "criterion": "pericarditis",
                    "requirements": [
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Documented myocardial infarction or arterial thrombotic events within 6 months prior to study enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Documented myocardial infarction",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 6,
                                        "unit": "months"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "arterial thrombotic events within 6 months prior to study enrollment",
                    "criterion": "arterial thrombotic events",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 6,
                                        "unit": "months"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of documented congestive heart failure (New York Health Association functional classification III to IV).",
            "criterions": [
                {
                    "exact_snippets": "History of documented congestive heart failure",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "New York Health Association functional classification III to IV",
                    "criterion": "New York Health Association functional classification",
                    "requirements": [
                        {
                            "requirement_type": "classification",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 3,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Documented history of cardiomyopathy.",
            "criterions": [
                {
                    "exact_snippets": "Documented history of cardiomyopathy",
                    "criterion": "cardiomyopathy",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known left ventricular ejection fraction <50% as determined by multiple gated acquisition scan or echocardiogram within 28 days prior to enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Known left ventricular ejection fraction <50%",
                    "criterion": "left ventricular ejection fraction",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "as determined by multiple gated acquisition scan or echocardiogram",
                    "criterion": "method of determination for left ventricular ejection fraction",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "multiple gated acquisition scan",
                                "echocardiogram"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "within 28 days prior to enrollment",
                    "criterion": "timeframe for left ventricular ejection fraction determination",
                    "requirements": [
                        {
                            "requirement_type": "timeframe",
                            "expected_value": "within 28 days prior to enrollment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of clinically significant cardiac arrhythmias unsuitable to participate, as determined by the investigator.",
            "criterions": [
                {
                    "exact_snippets": "History of clinically significant cardiac arrhythmias",
                    "criterion": "cardiac arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "clinically significant"
                        },
                        {
                            "requirement_type": "suitability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "16. Patients with a Fridericia-corrected QT (QTcF) interval of >470 msec on the screening ECG (using the QTcF formula), has a short/long QT syndrome, or history of QT prolongation/Torsades de Pointes, unless prolonged QTc interval is due to (right or left) bundle branch block and/or pacemaker rhythm. If wide QRS complex is present, cardiology consultation is required to assess the risk for Torsade de Pointes.",
            "criterions": [
                {
                    "exact_snippets": "Fridericia-corrected QT (QTcF) interval of >470 msec",
                    "criterion": "QTcF interval",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 470,
                                "unit": "msec"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "short/long QT syndrome",
                    "criterion": "QT syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of QT prolongation",
                    "criterion": "QT prolongation",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of ... Torsades de Pointes",
                    "criterion": "Torsades de Pointes",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "wide QRS complex is present",
                    "criterion": "wide QRS complex",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "17. Patients with a history of an active infection (viral, bacterial, or fungal) requiring systemic therapy within 10 days before enrollment, including but not limited to tuberculosis.",
            "criterions": [
                {
                    "exact_snippets": "history of an active infection (viral, bacterial, or fungal)",
                    "criterion": "active infection history",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "requiring systemic therapy within 10 days before enrollment",
                    "criterion": "systemic therapy for infection",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 10,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "18. Patients who have active human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infections.",
            "criterions": [
                {
                    "exact_snippets": "active human immunodeficiency virus (HIV)",
                    "criterion": "HIV infection",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "active"
                        }
                    ]
                },
                {
                    "exact_snippets": "active ... hepatitis B",
                    "criterion": "hepatitis B infection",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "active"
                        }
                    ]
                },
                {
                    "exact_snippets": "active ... hepatitis C",
                    "criterion": "hepatitis C infection",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "active"
                        }
                    ]
                }
            ]
        },
        {
            "line": "19. Patients that are currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzyme CYP1A (including but not limited:",
            "criterions": [
                {
                    "exact_snippets": "currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzyme CYP1A",
                    "criterion": "treatment with drugs affecting CYP1A",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "α-Naphthoflavone, Furafylline, Omeprazole, Lansoprazole) and isoenzyme CYP3A (including but not limited: Itraconazole, Ketoconazole, Azamulin, Troleandomycin, Verapamil, Rifampicin). The patients must have discontinued moderate or strong inducers for at least 2 weeks prior to study enrollment and must have discontinued moderate or strong inhibitors for at least 1 week before study enrollment. Spironolactone Strong bile salt export pump (BSEP) inhibitors, grapefruit juice, herbal medicines such as St. John's wort, Kava, ephedra, gingko biloba, dehydroepiandrosterone, yohimbe, saw palmetto and ginseng should be discontinued.",
            "criterions": [
                {
                    "exact_snippets": "discontinued moderate or strong inducers for at least 2 weeks prior to study enrollment",
                    "criterion": "use of moderate or strong inducers",
                    "requirements": [
                        {
                            "requirement_type": "discontinuation period",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "discontinued moderate or strong inhibitors for at least 1 week before study enrollment",
                    "criterion": "use of moderate or strong inhibitors",
                    "requirements": [
                        {
                            "requirement_type": "discontinuation period",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "week"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Spironolactone Strong bile salt export pump (BSEP) inhibitors, grapefruit juice, herbal medicines such as St. John's wort, Kava, ephedra, gingko biloba, dehydroepiandrosterone, yohimbe, saw palmetto and ginseng should be discontinued",
                    "criterion": "use of specific substances",
                    "requirements": [
                        {
                            "requirement_type": "discontinuation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "20. Sexually active males not willing to use a condom during the whole course of the study and for 16 weeks after stopping treatment. Male patients must not father a child in this period. A condom is required to be used also by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the drug via seminal fluid.",
            "criterions": [
                {
                    "exact_snippets": "Sexually active males not willing to use a condom during the whole course of the study and for 16 weeks after stopping treatment.",
                    "criterion": "condom use",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Male patients must not father a child in this period.",
                    "criterion": "fathering a child",
                    "requirements": [
                        {
                            "requirement_type": "prohibition",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "A condom is required to be used also by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the drug via seminal fluid.",
                    "criterion": "condom use by vasectomized men",
                    "requirements": [
                        {
                            "requirement_type": "requirement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "A condom is required to be used also by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the drug via seminal fluid.",
                    "criterion": "condom use during intercourse with a male partner",
                    "requirements": [
                        {
                            "requirement_type": "requirement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "21. Patients with any other medical, psychiatric, or social condition, including substance abuse, which in the opinion of the investigator, would preclude participation in the study.",
            "criterions": [
                {
                    "exact_snippets": "any other medical ... condition",
                    "criterion": "medical condition",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "any other ... psychiatric ... condition",
                    "criterion": "psychiatric condition",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "any other ... social condition",
                    "criterion": "social condition",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "substance abuse",
                    "criterion": "substance abuse",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "22. Patients with a history of upper gastrointestinal bleeding or uncontrolled peptic disease in the previous 3 months which in Investigator's opinion may impact patient's participation in the study.",
            "criterions": [
                {
                    "exact_snippets": "history of upper gastrointestinal bleeding",
                    "criterion": "upper gastrointestinal bleeding",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled peptic disease",
                    "criterion": "peptic disease",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "in the previous 3 months",
                    "criterion": "time since last occurrence",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "months"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "23. Patients have previously received AKT or PI3 kinase pathway or mTOR inhibitors",
            "criterions": [
                {
                    "exact_snippets": "Patients have previously received AKT",
                    "criterion": "AKT inhibitors",
                    "requirements": [
                        {
                            "requirement_type": "previous treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients have previously received ... PI3 kinase pathway",
                    "criterion": "PI3 kinase pathway inhibitors",
                    "requirements": [
                        {
                            "requirement_type": "previous treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients have previously received ... mTOR inhibitors",
                    "criterion": "mTOR inhibitors",
                    "requirements": [
                        {
                            "requirement_type": "previous treatment",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [
        {
            "line": "10. Patients with symptomatic or known central nervous system metastases from prostate cancer or who are at high risk for spinal cord compression, per investigator's judgment.",
            "criterions": [
                {
                    "exact_snippets": "Patients with symptomatic or known central nervous system metastases from prostate cancer",
                    "criterion": "central nervous system metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "patients ... who are at high risk for spinal cord compression, per investigator's judgment",
                    "criterion": "risk for spinal cord compression",
                    "requirements": [
                        {
                            "requirement_type": "risk level",
                            "expected_value": "high"
                        }
                    ]
                }
            ]
        }
    ],
    "failed_miscellaneous": []
}