{
    "info": {
        "nct_id": "NCT05808582",
        "official_title": "Multicenter, Single-arm, Open Clinical Study of Chidamide in Combination With Fulvestrant in HR+/HER2-advanced Breast Cancer That Has Failed Prior CDK4/6 Inhibitor Combined With Aromatase Inhibitor Therapy",
        "inclusion_criteria": "1. Age ≥ 18 years, female.\n2. Both postmenopausal and premenopausal for hormone receptor positive patients, but premenopausal patients need to be given concomitant ovarian function suppression (OFS) therapy (criteria for menopause: \"Judgment Criteria for Menopause after Adjuvant Therapy and Consensus on Clinical Application of Aromatase Inhibitors for Premenopausal Female Breast Cancer Patients in China\").\n3. Patients with HR-positive (ER-positive, PR-positive or negative) and HER2-negative breast cancer confirmed by histopathology, defined as follows.\n4. Pre-enrollment disease status of non-surgically resectable locally advanced or metastatic breast cancer.\n5. At least one extracranial measurable lesion as defined by RECIST V1.1 criteria or bone metastases alone.\n6. Progress after previous treatment with CDK4/6 inhibitor combined with any aromatase inhibitor (after previous treatment with CDK4/6 inhibitor combined with aromatase inhibitor, you can enter the study directly or re-enter the group after chemotherapy); ; The total number of previous rescue treatments is ≤3; Previously received rescue chemotherapy ≤1 line; Time interval from the last treatment: (a) If the last treatment is endocrine therapy, it needs ≥2 weeks; (b) If the last treatment is chemotherapy, it needs ≥4 weeks;\n7. ECOG PS score: 0-1.\n8. Organ function meets the requirement.\n9. expected survival ≥ 3 months.\n10. Subjects of childbearing potential need to have a negative pregnancy test within 7 days prior to initiation of treatment and must use an appropriate method of contraception during treatment and for three months after completion of treatment.\n11. Patients are fully informed and voluntarily sign an informed consent form.\nHealthy volunteers allowed\nMust be FEMALE\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Prior treatment with any HDAC inhibitor or fulvestrant.\n2. known hypersensitivity to the drug components of this trial.\n3. have inflammatory breast cancer at the time of screening\n4. clinical evidence or history of central nervous system metastases (CS) and/or carcinomatous meningitis, soft meningeal disease\n5. inability or unwillingness to swallow medications or receive intramuscular injections\n6. have gastrointestinal insufficiency or gastrointestinal disease that can significantly interfere with the absorption of study drug (e.g., uncontrolled ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)\n7. History of immunodeficiency, including testing positive for HIV, or having other acquired or congenital immunodeficiency disorders, or a history of organ transplantation.\n8. other malignancies (except cured basal cell carcinoma of the skin, cervical carcinoma in situ and thyroid cancer) within the previous 5 years or concurrently\n9. having undergone a major surgical operation or significant trauma within 4 weeks prior to initiation of treatment, or where the patient is expected to undergo major surgical treatment\n10. Inability to understand or follow study guidelines and requirements.\n11. Those who are judged by the investigator to be unsuitable for participation in this study.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Age ≥ 18 years, female.",
            "criterions": [
                {
                    "exact_snippets": "Age ≥ 18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "female",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "gender",
                            "expected_value": "female"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Both postmenopausal and premenopausal for hormone receptor positive patients, but premenopausal patients need to be given concomitant ovarian function suppression (OFS) therapy (criteria for menopause: \"Judgment Criteria for Menopause after Adjuvant Therapy and Consensus on Clinical Application of Aromatase Inhibitors for Premenopausal Female Breast Cancer Patients in China\").",
            "criterions": [
                {
                    "exact_snippets": "postmenopausal",
                    "criterion": "menopausal status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "postmenopausal"
                        }
                    ]
                },
                {
                    "exact_snippets": "premenopausal",
                    "criterion": "menopausal status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "premenopausal"
                        }
                    ]
                },
                {
                    "exact_snippets": "hormone receptor positive",
                    "criterion": "hormone receptor status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "premenopausal patients need to be given concomitant ovarian function suppression (OFS) therapy",
                    "criterion": "ovarian function suppression therapy",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patients with HR-positive (ER-positive, PR-positive or negative) and HER2-negative breast cancer confirmed by histopathology, defined as follows.",
            "criterions": [
                {
                    "exact_snippets": "HR-positive (ER-positive, PR-positive or negative)",
                    "criterion": "hormone receptor status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "ER-positive",
                                "PR-positive",
                                "PR-negative"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "HER2-negative breast cancer",
                    "criterion": "HER2 status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "confirmed by histopathology",
                    "criterion": "confirmation method",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "histopathology"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Pre-enrollment disease status of non-surgically resectable locally advanced or metastatic breast cancer.",
            "criterions": [
                {
                    "exact_snippets": "non-surgically resectable",
                    "criterion": "disease resectability",
                    "requirements": [
                        {
                            "requirement_type": "resectability",
                            "expected_value": "non-surgically resectable"
                        }
                    ]
                },
                {
                    "exact_snippets": "locally advanced",
                    "criterion": "disease stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "locally advanced"
                        }
                    ]
                },
                {
                    "exact_snippets": "metastatic breast cancer",
                    "criterion": "disease type",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": "metastatic breast cancer"
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. At least one extracranial measurable lesion as defined by RECIST V1.1 criteria or bone metastases alone.",
            "criterions": [
                {
                    "exact_snippets": "At least one extracranial measurable lesion as defined by RECIST V1.1 criteria",
                    "criterion": "extracranial measurable lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "N/A"
                            }
                        },
                        {
                            "requirement_type": "definition",
                            "expected_value": "RECIST V1.1 criteria"
                        }
                    ]
                },
                {
                    "exact_snippets": "bone metastases alone",
                    "criterion": "bone metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Progress after previous treatment with CDK4/6 inhibitor combined with any aromatase inhibitor (after previous treatment with CDK4/6 inhibitor combined with aromatase inhibitor, you can enter the study directly or re-enter the group after chemotherapy); ; The total number of previous rescue treatments is ≤3; Previously received rescue chemotherapy ≤1 line; Time interval from the last treatment: (a) If the last treatment is endocrine therapy, it needs ≥2 weeks; (b) If the last treatment is chemotherapy, it needs ≥4 weeks;",
            "criterions": [
                {
                    "exact_snippets": "Progress after previous treatment with CDK4/6 inhibitor combined with any aromatase inhibitor",
                    "criterion": "progress after CDK4/6 inhibitor and aromatase inhibitor treatment",
                    "requirements": [
                        {
                            "requirement_type": "progress",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "The total number of previous rescue treatments is ≤3",
                    "criterion": "total number of previous rescue treatments",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Previously received rescue chemotherapy ≤1 line",
                    "criterion": "previous rescue chemotherapy lines",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "line"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Time interval from the last treatment: (a) If the last treatment is endocrine therapy, it needs ≥2 weeks",
                    "criterion": "time interval from last endocrine therapy",
                    "requirements": [
                        {
                            "requirement_type": "time interval",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Time interval from the last treatment: ... (b) If the last treatment is chemotherapy, it needs ≥4 weeks",
                    "criterion": "time interval from last chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time interval",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. ECOG PS score: 0-1.",
            "criterions": [
                {
                    "exact_snippets": "ECOG PS score: 0-1",
                    "criterion": "ECOG PS score",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 1,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Organ function meets the requirement.",
            "criterions": [
                {
                    "exact_snippets": "Organ function meets the requirement.",
                    "criterion": "organ function",
                    "requirements": [
                        {
                            "requirement_type": "meets requirement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. expected survival ≥ 3 months.",
            "criterions": [
                {
                    "exact_snippets": "expected survival ≥ 3 months",
                    "criterion": "expected survival",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Subjects of childbearing potential need to have a negative pregnancy test within 7 days prior to initiation of treatment and must use an appropriate method of contraception during treatment and for three months after completion of treatment.",
            "criterions": [
                {
                    "exact_snippets": "Subjects of childbearing potential",
                    "criterion": "childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "negative pregnancy test within 7 days prior to initiation of treatment",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        },
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 7 days prior to initiation of treatment"
                        }
                    ]
                },
                {
                    "exact_snippets": "must use an appropriate method of contraception during treatment and for three months after completion of treatment",
                    "criterion": "contraception",
                    "requirements": [
                        {
                            "requirement_type": "usage",
                            "expected_value": "during treatment and for three months after completion of treatment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Patients are fully informed and voluntarily sign an informed consent form.",
            "criterions": [
                {
                    "exact_snippets": "Patients are fully informed",
                    "criterion": "patient information status",
                    "requirements": [
                        {
                            "requirement_type": "information status",
                            "expected_value": "fully informed"
                        }
                    ]
                },
                {
                    "exact_snippets": "voluntarily sign an informed consent form",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "signed",
                            "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 FEMALE",
            "criterions": [
                {
                    "exact_snippets": "Must be FEMALE",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": "female"
                        }
                    ]
                }
            ]
        },
        {
            "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. Prior treatment with any HDAC inhibitor or fulvestrant.",
            "criterions": [
                {
                    "exact_snippets": "Prior treatment with any HDAC inhibitor",
                    "criterion": "HDAC inhibitor treatment",
                    "requirements": [
                        {
                            "requirement_type": "prior treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior treatment with ... fulvestrant",
                    "criterion": "fulvestrant treatment",
                    "requirements": [
                        {
                            "requirement_type": "prior treatment",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. known hypersensitivity to the drug components of this trial.",
            "criterions": [
                {
                    "exact_snippets": "known hypersensitivity to the drug components",
                    "criterion": "hypersensitivity to drug components",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. have inflammatory breast cancer at the time of screening",
            "criterions": [
                {
                    "exact_snippets": "inflammatory breast cancer at the time of screening",
                    "criterion": "inflammatory breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. clinical evidence or history of central nervous system metastases (CS) and/or carcinomatous meningitis, soft meningeal disease",
            "criterions": [
                {
                    "exact_snippets": "clinical evidence or history of central nervous system metastases",
                    "criterion": "central nervous system metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "clinical evidence or history of ... carcinomatous meningitis",
                    "criterion": "carcinomatous meningitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "clinical evidence or history of ... soft meningeal disease",
                    "criterion": "soft meningeal disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. inability or unwillingness to swallow medications or receive intramuscular injections",
            "criterions": [
                {
                    "exact_snippets": "inability or unwillingness to swallow medications",
                    "criterion": "ability to swallow medications",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "inability or unwillingness to ... receive intramuscular injections",
                    "criterion": "ability to receive intramuscular injections",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. History of immunodeficiency, including testing positive for HIV, or having other acquired or congenital immunodeficiency disorders, or a history of organ transplantation.",
            "criterions": [
                {
                    "exact_snippets": "History of immunodeficiency",
                    "criterion": "immunodeficiency",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "testing positive for HIV",
                    "criterion": "HIV status",
                    "requirements": [
                        {
                            "requirement_type": "positive",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "having other acquired or congenital immunodeficiency disorders",
                    "criterion": "acquired or congenital immunodeficiency disorders",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of organ transplantation",
                    "criterion": "organ transplantation",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. other malignancies (except cured basal cell carcinoma of the skin, cervical carcinoma in situ and thyroid cancer) within the previous 5 years or concurrently",
            "criterions": [
                {
                    "exact_snippets": "other malignancies ... within the previous 5 years",
                    "criterion": "other malignancies",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within the previous 5 years"
                        }
                    ]
                },
                {
                    "exact_snippets": "other malignancies ... concurrently",
                    "criterion": "other malignancies",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "except cured basal cell carcinoma of the skin",
                    "criterion": "cured basal cell carcinoma of the skin",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "except ... cervical carcinoma in situ",
                    "criterion": "cervical carcinoma in situ",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "except ... thyroid cancer",
                    "criterion": "thyroid cancer",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. having undergone a major surgical operation or significant trauma within 4 weeks prior to initiation of treatment, or where the patient is expected to undergo major surgical treatment",
            "criterions": [
                {
                    "exact_snippets": "having undergone a major surgical operation or significant trauma within 4 weeks prior to initiation of treatment",
                    "criterion": "major surgical operation or significant trauma",
                    "requirements": [
                        {
                            "requirement_type": "time since occurrence",
                            "expected_value": {
                                "operator": "<",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "where the patient is expected to undergo major surgical treatment",
                    "criterion": "expected to undergo major surgical treatment",
                    "requirements": [
                        {
                            "requirement_type": "expectation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Inability to understand or follow study guidelines and requirements.",
            "criterions": [
                {
                    "exact_snippets": "Inability to understand or follow study guidelines and requirements.",
                    "criterion": "ability to understand or follow study guidelines and requirements",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Those who are judged by the investigator to be unsuitable for participation in this study.",
            "criterions": [
                {
                    "exact_snippets": "judged by the investigator to be unsuitable for participation",
                    "criterion": "suitability for participation",
                    "requirements": [
                        {
                            "requirement_type": "judgment",
                            "expected_value": "suitable"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [
        {
            "line": "6. have gastrointestinal insufficiency or gastrointestinal disease that can significantly interfere with the absorption of study drug (e.g., uncontrolled ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)",
            "criterions": [
                {
                    "exact_snippets": "gastrointestinal insufficiency",
                    "criterion": "gastrointestinal insufficiency",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "gastrointestinal disease that can significantly interfere with the absorption of study drug",
                    "criterion": "gastrointestinal disease",
                    "requirements": [
                        {
                            "requirement_type": "interference with drug absorption",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled ulcerative disease",
                    "criterion": "ulcerative disease",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled nausea",
                    "criterion": "nausea",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled vomiting",
                    "criterion": "vomiting",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled ... diarrhea",
                    "criterion": "diarrhea",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "malabsorption syndrome",
                    "criterion": "malabsorption syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "small bowel resection",
                    "criterion": "small bowel resection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "failed_miscellaneous": []
}