{
    "info": {
        "nct_id": "NCT05241860",
        "official_title": "A Phase 2 Trial of ADT Interruption in Patients Responding Exceptionally to AR-Pathway Inhibitor in Metastatic Hormone-Sensitive Prostate Cancer (MHSPC): A-DREAM",
        "inclusion_criteria": "* Histologic or clinical diagnosis of metastatic prostate cancer\n* Must have had evidence of metastatic disease by bone scan, or nodal or visceral lesions on computed tomography (CT) or magnetic resonance imaging (MRI) prior to starting on intense antiandrogen therapy (ADT)\n\n  * Radiographic evidence of disease is not required at the time of enrollment\n  * No metastases to liver or to brain, as these represent aggressive variant disease biology for which intermittent treatment may not be favored\n* Must currently be receiving intense ADT for metastatic hormone sensitive prostate cancer (mHSPC)\n\n  * Testosterone suppression (TS) with luteinizing hormone releasing hormone (LHRH)-agonist or LHRH-antagonist AND\n  * An approved secondary androgen receptor pathway inhibitor (ARPI) abiraterone, enzalutamide, or apalutamide (or darolutamide if approved for this indication)\n* Must have remained on testosterone suppression for metastatic disease continuously (without treatment breaks) for 540-750 days (approximately 18 to 24 months) from time of first dose of LHRH agonist or antagonist by time of registration. A period of anti-androgen treatment prior to LHRH agonist or antagonist initiation is not included in the 540 - 750 days (approximately 18 to 24 months)\n* Must have received treatment with ARPI for at least 360 days in total by time of A032101 registration. Treatment breaks from ARPI of up to 28 days are permitted (for example peri-procedural or for management of a temporary adverse event) as long as PSA did not rise while holding therapy\n* Prior TS in the context of neoadjuvant/concurrent/adjuvant treatment with local therapy is permitted. Prior course(s) of intermittent TS for biochemical-only recurrence is permitted. However, if the patient previously received TS, metastatic progression for which intense ADT was initiated must have occurred during an off-treatment interval and with testosterone >= 150 ng/dL\n* Prior local therapy for prostate cancer (either before or after diagnosis of metastatic disease) is permitted. Prior treatment with docetaxel chemotherapy for up to 6 cycles is permitted. Prior radiation therapy to metastatic sites (either for symptom palliation or for ablation of oligometastatic disease) is permitted\nHealthy volunteers allowed\nMust be MALE\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* No history of surgical castration\n* No history of ARPI use prior to diagnosis of mHSPC for which the patient is currently receiving intense ADT (such as in the neoadjuvant setting with prior local therapy)\n* No current or prior treatment with experimental agents for metastatic hormone-sensitive prostate cancer\n* Eastern Cooperative Oncology Group (ECOG) performance status 0-2\n* Prior to initiating intense ADT\n\n  * Prostate specific antigen (PSA) >= 5 ng/ml\n  * Testosterone >= 150 ng/dl. Patients are permitted to enroll if testosterone was not measured prior to initiating intense ADT for mHSPC if they did not previously receive TS and were not known or suspected to be hypogonadal at the time\n* At time of enrollment to A032101\n\n  * PSA < 0.2 ng/ml\n\n    ** PSA values (measured in the same laboratory) must be stable or falling for 3 consecutive measurements - i.e. any PSA rise must be followed by a decrease in PSA that is further decreased or stable on a 3rd measurement. Any patient with 2 consecutive rises in PSA values since achieving castrate level of testosterone is not eligible\n  * Testosterone < 50 ng/dl\n* No current participation in a clinical study that does not allow for TS or ARPI interruption\n* No patients with a \"currently active\" second malignancy * Patients with non-melanomatous skin cancer, superficial bladder cancer, cancer not needing active therapy for at least 2 years, cancer for which the treating investigator deems the subject",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Histologic or clinical diagnosis of metastatic prostate cancer",
            "criterions": [
                {
                    "exact_snippets": "Histologic or clinical diagnosis of metastatic prostate cancer",
                    "criterion": "metastatic prostate cancer",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis",
                            "expected_value": [
                                "histologic",
                                "clinical"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Must have had evidence of metastatic disease by bone scan, or nodal or visceral lesions on computed tomography (CT) or magnetic resonance imaging (MRI) prior to starting on intense antiandrogen therapy (ADT)",
            "criterions": [
                {
                    "exact_snippets": "evidence of metastatic disease by bone scan",
                    "criterion": "metastatic disease",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "nodal or visceral lesions on computed tomography (CT) or magnetic resonance imaging (MRI)",
                    "criterion": "nodal or visceral lesions",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Radiographic evidence of disease is not required at the time of enrollment",
            "criterions": [
                {
                    "exact_snippets": "Radiographic evidence of disease is not required",
                    "criterion": "radiographic evidence of disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No metastases to liver or to brain, as these represent aggressive variant disease biology for which intermittent treatment may not be favored",
            "criterions": [
                {
                    "exact_snippets": "No metastases to liver",
                    "criterion": "metastases to liver",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "No metastases to ... brain",
                    "criterion": "metastases to brain",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Must currently be receiving intense ADT for metastatic hormone sensitive prostate cancer (mHSPC)",
            "criterions": [
                {
                    "exact_snippets": "Must currently be receiving intense ADT",
                    "criterion": "ADT treatment",
                    "requirements": [
                        {
                            "requirement_type": "intensity",
                            "expected_value": "intense"
                        },
                        {
                            "requirement_type": "current status",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "metastatic hormone sensitive prostate cancer (mHSPC)",
                    "criterion": "prostate cancer",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "metastatic"
                        },
                        {
                            "requirement_type": "hormone sensitivity",
                            "expected_value": "sensitive"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Testosterone suppression (TS) with luteinizing hormone releasing hormone (LHRH)-agonist or LHRH-antagonist AND",
            "criterions": [
                {
                    "exact_snippets": "Testosterone suppression (TS) with luteinizing hormone releasing hormone (LHRH)-agonist or LHRH-antagonist",
                    "criterion": "testosterone suppression",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "luteinizing hormone releasing hormone (LHRH)-agonist",
                                "LHRH-antagonist"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* An approved secondary androgen receptor pathway inhibitor (ARPI) abiraterone, enzalutamide, or apalutamide (or darolutamide if approved for this indication)",
            "criterions": [
                {
                    "exact_snippets": "An approved secondary androgen receptor pathway inhibitor (ARPI) abiraterone, enzalutamide, or apalutamide (or darolutamide if approved for this indication)",
                    "criterion": "secondary androgen receptor pathway inhibitor",
                    "requirements": [
                        {
                            "requirement_type": "approval",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "specific drugs",
                            "expected_value": [
                                "abiraterone",
                                "enzalutamide",
                                "apalutamide",
                                "darolutamide"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Must have remained on testosterone suppression for metastatic disease continuously (without treatment breaks) for 540-750 days (approximately 18 to 24 months) from time of first dose of LHRH agonist or antagonist by time of registration. A period of anti-androgen treatment prior to LHRH agonist or antagonist initiation is not included in the 540 - 750 days (approximately 18 to 24 months)",
            "criterions": [
                {
                    "exact_snippets": "Must have remained on testosterone suppression for metastatic disease continuously (without treatment breaks)",
                    "criterion": "testosterone suppression for metastatic disease",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 540,
                                        "unit": "days"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 750,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "A period of anti-androgen treatment prior to LHRH agonist or antagonist initiation is not included",
                    "criterion": "anti-androgen treatment prior to LHRH agonist or antagonist initiation",
                    "requirements": [
                        {
                            "requirement_type": "inclusion",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Must have received treatment with ARPI for at least 360 days in total by time of A032101 registration. Treatment breaks from ARPI of up to 28 days are permitted (for example peri-procedural or for management of a temporary adverse event) as long as PSA did not rise while holding therapy",
            "criterions": [
                {
                    "exact_snippets": "Must have received treatment with ARPI for at least 360 days in total",
                    "criterion": "ARPI treatment duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 360,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Treatment breaks from ARPI of up to 28 days are permitted",
                    "criterion": "ARPI treatment break duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "as long as PSA did not rise while holding therapy",
                    "criterion": "PSA level during ARPI treatment break",
                    "requirements": [
                        {
                            "requirement_type": "change",
                            "expected_value": "did not rise"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior TS in the context of neoadjuvant/concurrent/adjuvant treatment with local therapy is permitted. Prior course(s) of intermittent TS for biochemical-only recurrence is permitted. However, if the patient previously received TS, metastatic progression for which intense ADT was initiated must have occurred during an off-treatment interval and with testosterone >= 150 ng/dL",
            "criterions": [
                {
                    "exact_snippets": "Prior TS in the context of neoadjuvant/concurrent/adjuvant treatment with local therapy is permitted.",
                    "criterion": "prior TS in the context of neoadjuvant/concurrent/adjuvant treatment with local therapy",
                    "requirements": [
                        {
                            "requirement_type": "permitted",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior course(s) of intermittent TS for biochemical-only recurrence is permitted.",
                    "criterion": "prior course(s) of intermittent TS for biochemical-only recurrence",
                    "requirements": [
                        {
                            "requirement_type": "permitted",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "if the patient previously received TS, metastatic progression for which intense ADT was initiated must have occurred during an off-treatment interval",
                    "criterion": "metastatic progression during an off-treatment interval",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "must have occurred"
                        }
                    ]
                },
                {
                    "exact_snippets": "testosterone >= 150 ng/dL",
                    "criterion": "testosterone level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 150,
                                "unit": "ng/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior local therapy for prostate cancer (either before or after diagnosis of metastatic disease) is permitted. Prior treatment with docetaxel chemotherapy for up to 6 cycles is permitted. Prior radiation therapy to metastatic sites (either for symptom palliation or for ablation of oligometastatic disease) is permitted",
            "criterions": [
                {
                    "exact_snippets": "Prior local therapy for prostate cancer ... is permitted",
                    "criterion": "prior local therapy for prostate cancer",
                    "requirements": [
                        {
                            "requirement_type": "permitted",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior treatment with docetaxel chemotherapy for up to 6 cycles is permitted",
                    "criterion": "prior treatment with docetaxel chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "permitted",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "maximum cycles",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "cycles"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior radiation therapy to metastatic sites ... is permitted",
                    "criterion": "prior radiation therapy to metastatic sites",
                    "requirements": [
                        {
                            "requirement_type": "permitted",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must be MALE",
            "criterions": [
                {
                    "exact_snippets": "Must be MALE",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "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": "* No history of surgical castration",
            "criterions": [
                {
                    "exact_snippets": "No history of surgical castration",
                    "criterion": "surgical castration",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No history of ARPI use prior to diagnosis of mHSPC for which the patient is currently receiving intense ADT (such as in the neoadjuvant setting with prior local therapy)",
            "criterions": [
                {
                    "exact_snippets": "No history of ARPI use prior to diagnosis of mHSPC",
                    "criterion": "ARPI use history",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "patient is currently receiving intense ADT",
                    "criterion": "intense ADT",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No current or prior treatment with experimental agents for metastatic hormone-sensitive prostate cancer",
            "criterions": [
                {
                    "exact_snippets": "No current or prior treatment with experimental agents",
                    "criterion": "treatment with experimental agents",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "metastatic hormone-sensitive prostate cancer",
                    "criterion": "metastatic hormone-sensitive prostate cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Eastern Cooperative Oncology Group (ECOG) performance status 0-2",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status 0-2",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior to initiating intense ADT",
            "criterions": [
                {
                    "exact_snippets": "initiating intense ADT",
                    "criterion": "intense ADT",
                    "requirements": [
                        {
                            "requirement_type": "initiation",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prostate specific antigen (PSA) >= 5 ng/ml",
            "criterions": [
                {
                    "exact_snippets": "Prostate specific antigen (PSA) >= 5 ng/ml",
                    "criterion": "Prostate specific antigen (PSA)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 5,
                                "unit": "ng/ml"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Testosterone >= 150 ng/dl. Patients are permitted to enroll if testosterone was not measured prior to initiating intense ADT for mHSPC if they did not previously receive TS and were not known or suspected to be hypogonadal at the time",
            "criterions": [
                {
                    "exact_snippets": "Testosterone >= 150 ng/dl",
                    "criterion": "testosterone level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 150,
                                "unit": "ng/dl"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "testosterone was not measured prior to initiating intense ADT for mHSPC",
                    "criterion": "testosterone measurement",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "not measured prior to initiating intense ADT for mHSPC"
                        }
                    ]
                },
                {
                    "exact_snippets": "if they did not previously receive TS",
                    "criterion": "testosterone suppression (TS)",
                    "requirements": [
                        {
                            "requirement_type": "treatment history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "were not known or suspected to be hypogonadal at the time",
                    "criterion": "hypogonadism",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* At time of enrollment to A032101",
            "criterions": [
                {
                    "exact_snippets": "At time of enrollment to A032101",
                    "criterion": "enrollment to A032101",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* PSA < 0.2 ng/ml",
            "criterions": [
                {
                    "exact_snippets": "PSA < 0.2 ng/ml",
                    "criterion": "PSA level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 0.2,
                                "unit": "ng/ml"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "** PSA values (measured in the same laboratory) must be stable or falling for 3 consecutive measurements - i.e. any PSA rise must be followed by a decrease in PSA that is further decreased or stable on a 3rd measurement. Any patient with 2 consecutive rises in PSA values since achieving castrate level of testosterone is not eligible",
            "criterions": [
                {
                    "exact_snippets": "PSA values ... must be stable or falling for 3 consecutive measurements",
                    "criterion": "PSA values",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": "stable or falling for 3 consecutive measurements"
                        }
                    ]
                },
                {
                    "exact_snippets": "PSA rise must be followed by a decrease in PSA that is further decreased or stable on a 3rd measurement",
                    "criterion": "PSA rise",
                    "requirements": [
                        {
                            "requirement_type": "pattern",
                            "expected_value": "followed by a decrease and further decreased or stable on a 3rd measurement"
                        }
                    ]
                },
                {
                    "exact_snippets": "patient with 2 consecutive rises in PSA values since achieving castrate level of testosterone is not eligible",
                    "criterion": "PSA values",
                    "requirements": [
                        {
                            "requirement_type": "pattern",
                            "expected_value": "2 consecutive rises since achieving castrate level of testosterone"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Testosterone < 50 ng/dl",
            "criterions": [
                {
                    "exact_snippets": "Testosterone < 50 ng/dl",
                    "criterion": "testosterone level",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 50,
                                "unit": "ng/dl"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No current participation in a clinical study that does not allow for TS or ARPI interruption",
            "criterions": [
                {
                    "exact_snippets": "No current participation in a clinical study that does not allow for TS or ARPI interruption",
                    "criterion": "current participation in a clinical study",
                    "requirements": [
                        {
                            "requirement_type": "allowance for TS or ARPI interruption",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No patients with a \"currently active\" second malignancy * Patients with non-melanomatous skin cancer, superficial bladder cancer, cancer not needing active therapy for at least 2 years, cancer for which the treating investigator deems the subject",
            "criterions": [
                {
                    "exact_snippets": "No patients with a \"currently active\" second malignancy",
                    "criterion": "second malignancy",
                    "requirements": [
                        {
                            "requirement_type": "activity status",
                            "expected_value": "not currently active"
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients with non-melanomatous skin cancer",
                    "criterion": "non-melanomatous skin cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "superficial bladder cancer",
                    "criterion": "superficial bladder cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "cancer not needing active therapy for at least 2 years",
                    "criterion": "cancer",
                    "requirements": [
                        {
                            "requirement_type": "therapy requirement",
                            "expected_value": "not needing active therapy for at least 2 years"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}