{
    "info": {
        "nct_id": "NCT02308020",
        "official_title": "A Phase 2 Study of Abemaciclib in Patients With Brain Metastases Secondary to Hormone Receptor Positive Breast Cancer, Non-small Cell Lung Cancer, or Melanoma",
        "inclusion_criteria": "* Have brain metastases secondary to hormone receptor positive breast cancer, NSCLC, or melanoma.\n* Have either human epidermal growth factor receptor 2 positive (HER2+) (Study Part A) or negative HER2- (Study Part B) breast cancer.\n* Participants in Study Part C must have HR+ breast cancer, NSCLC, or melanoma with brain lesions clinically indicated for surgical resection as well as consent to provide tissue for drug concentration determination after 5 to 14 days of study drug dosing.\n* Participants in Part D must have NSCLC of any subtype.\n* Participants in Part E must have melanoma of any subtype.\n* Participants in Part F must have HR+ breast cancer, NSCLC, or melanoma with leptomeningeal metastases.\n* For Parts A, B, D, and E: Must have at least 1 measurable brain lesion ≥10 millimeters (mm) in the longest diameter (LD).\n* For Part C (surgical): Have metastatic brain lesion(s) for which surgical resection is clinically indicated.\n* Have completed local therapy (surgical resection, whole-breast radiotherapy (WBRT), or SRS) ≥14 days prior to initiating abemaciclib and recovered from all acute effects.\n* If receiving concomitant corticosteroids, must be on a stable or decreasing dose for at least 7 days prior to the baseline Gd-MRI.\n* Have a Karnofsky performance status of ≥70.\n* Have a life expectancy ≥12 weeks.\n* For HR+ breast cancer participants in part A, B, C, and F: If currently receiving endocrine therapy, a participant may continue to receive the same endocrine therapy provided that extracranial disease is stable for at least 3 months and central nervous system (CNS) disease progression has occurred while on this endocrine therapy. If these conditions are not met, participants must discontinue endocrine therapy prior to initiation of abemaciclib.\n* For HER2+ breast cancer participants in parts A, C, and F: participants may receive concurrent treatment (ongoing or initiated simultaneously with abemaciclib) with IV trastuzumab.\n* For NSCLC participants in parts C, D, and F: if currently receiving gemcitabine or pemetrexed (single-agent or in combination with another therapy), a participant may continue to receive 1 of these 2 therapies provided that extracranial disease is stable for at least 6 weeks and CNS disease progression has occurred while on this therapy.\n* Have adequate organ function.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Require immediate local therapy, including but not limited to WBRT, SRS, or surgical resection, for treatment of brain metastases.\n* Are taking concurrent enzyme-inducing antiepileptic drugs (EIAED).\n* Have evidence of significant (ie, symptomatic) intracranial hemorrhage.\n* For Parts A, B, C, D, E: Have evidence of leptomeningeal metastases. Note: discrete dural metastases are permitted.\n* Have experienced >2 seizures within 4 weeks prior to study entry.\n* For Parts A, B, D, E, and F: Have previously received treatment with any cyclin dependent kinase 6 (CDK6) inhibitor. For Part C participants may have received prior palbociclib or ribociclib, but not abemaciclib treatment.\n* Have known contraindication to Gd-MRI.\n* Have a preexisting chronic condition resulting in persistent diarrhea.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Have brain metastases secondary to hormone receptor positive breast cancer, NSCLC, or melanoma.",
            "criterions": [
                {
                    "exact_snippets": "brain metastases",
                    "criterion": "brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "hormone receptor positive breast cancer",
                    "criterion": "hormone receptor positive breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "NSCLC",
                    "criterion": "NSCLC",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "melanoma",
                    "criterion": "melanoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Have either human epidermal growth factor receptor 2 positive (HER2+) (Study Part A) or negative HER2- (Study Part B) breast cancer.",
            "criterions": [
                {
                    "exact_snippets": "human epidermal growth factor receptor 2 positive (HER2+) (Study Part A)",
                    "criterion": "HER2 status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "negative HER2- (Study Part B)",
                    "criterion": "HER2 status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "breast cancer",
                    "criterion": "breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants in Study Part C must have HR+ breast cancer, NSCLC, or melanoma with brain lesions clinically indicated for surgical resection as well as consent to provide tissue for drug concentration determination after 5 to 14 days of study drug dosing.",
            "criterions": [
                {
                    "exact_snippets": "HR+ breast cancer",
                    "criterion": "breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "hormone receptor status",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "NSCLC",
                    "criterion": "non-small cell lung cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "melanoma",
                    "criterion": "melanoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "brain lesions clinically indicated for surgical resection",
                    "criterion": "brain lesions",
                    "requirements": [
                        {
                            "requirement_type": "surgical indication",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "consent to provide tissue for drug concentration determination",
                    "criterion": "consent to provide tissue",
                    "requirements": [
                        {
                            "requirement_type": "consent",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "after 5 to 14 days of study drug dosing",
                    "criterion": "study drug dosing duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 5,
                                        "unit": "days"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 14,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants in Part D must have NSCLC of any subtype.",
            "criterions": [
                {
                    "exact_snippets": "Participants in Part D must have NSCLC",
                    "criterion": "NSCLC",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants in Part E must have melanoma of any subtype.",
            "criterions": [
                {
                    "exact_snippets": "melanoma of any subtype",
                    "criterion": "melanoma",
                    "requirements": [
                        {
                            "requirement_type": "subtype",
                            "expected_value": "any"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants in Part F must have HR+ breast cancer, NSCLC, or melanoma with leptomeningeal metastases.",
            "criterions": [
                {
                    "exact_snippets": "Participants in Part F must have HR+ breast cancer",
                    "criterion": "HR+ breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Participants in Part F must have ... NSCLC",
                    "criterion": "NSCLC",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Participants in Part F must have ... melanoma with leptomeningeal metastases",
                    "criterion": "melanoma with leptomeningeal metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* For Parts A, B, D, and E: Must have at least 1 measurable brain lesion ≥10 millimeters (mm) in the longest diameter (LD).",
            "criterions": [
                {
                    "exact_snippets": "at least 1 measurable brain lesion ≥10 millimeters (mm) in the longest diameter (LD)",
                    "criterion": "brain lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "lesion"
                            }
                        },
                        {
                            "requirement_type": "measurability",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "size",
                            "expected_value": {
                                "operator": ">=",
                                "value": 10,
                                "unit": "millimeters"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* For Part C (surgical): Have metastatic brain lesion(s) for which surgical resection is clinically indicated.",
            "criterions": [
                {
                    "exact_snippets": "metastatic brain lesion(s)",
                    "criterion": "metastatic brain lesions",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "surgical resection is clinically indicated",
                    "criterion": "surgical resection indication",
                    "requirements": [
                        {
                            "requirement_type": "indication",
                            "expected_value": "clinically indicated"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Have completed local therapy (surgical resection, whole-breast radiotherapy (WBRT), or SRS) ≥14 days prior to initiating abemaciclib and recovered from all acute effects.",
            "criterions": [
                {
                    "exact_snippets": "Have completed local therapy (surgical resection, whole-breast radiotherapy (WBRT), or SRS)",
                    "criterion": "local therapy",
                    "requirements": [
                        {
                            "requirement_type": "completion",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "≥14 days prior to initiating abemaciclib",
                    "criterion": "time since local therapy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "recovered from all acute effects",
                    "criterion": "recovery from acute effects",
                    "requirements": [
                        {
                            "requirement_type": "recovery",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* If receiving concomitant corticosteroids, must be on a stable or decreasing dose for at least 7 days prior to the baseline Gd-MRI.",
            "criterions": [
                {
                    "exact_snippets": "receiving concomitant corticosteroids",
                    "criterion": "concomitant corticosteroids",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "stable or decreasing dose for at least 7 days",
                    "criterion": "corticosteroid dose stability",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": "stable or decreasing"
                        },
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 7,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Have a Karnofsky performance status of ≥70.",
            "criterions": [
                {
                    "exact_snippets": "Karnofsky performance status of ≥70",
                    "criterion": "Karnofsky performance status",
                    "requirements": [
                        {
                            "requirement_type": "performance status",
                            "expected_value": {
                                "operator": ">=",
                                "value": 70,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Have a life expectancy ≥12 weeks.",
            "criterions": [
                {
                    "exact_snippets": "life expectancy ≥12 weeks",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "N/A",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* For HR+ breast cancer participants in part A, B, C, and F: If currently receiving endocrine therapy, a participant may continue to receive the same endocrine therapy provided that extracranial disease is stable for at least 3 months and central nervous system (CNS) disease progression has occurred while on this endocrine therapy. If these conditions are not met, participants must discontinue endocrine therapy prior to initiation of abemaciclib.",
            "criterions": [
                {
                    "exact_snippets": "HR+ breast cancer participants",
                    "criterion": "HR+ breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "currently receiving endocrine therapy",
                    "criterion": "current endocrine therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "extracranial disease is stable for at least 3 months",
                    "criterion": "extracranial disease stability",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "central nervous system (CNS) disease progression has occurred while on this endocrine therapy",
                    "criterion": "CNS disease progression",
                    "requirements": [
                        {
                            "requirement_type": "progression",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* For HER2+ breast cancer participants in parts A, C, and F: participants may receive concurrent treatment (ongoing or initiated simultaneously with abemaciclib) with IV trastuzumab.",
            "criterions": [
                {
                    "exact_snippets": "HER2+ breast cancer participants",
                    "criterion": "HER2+ breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "participants may receive concurrent treatment ... with IV trastuzumab",
                    "criterion": "concurrent treatment with IV trastuzumab",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* For NSCLC participants in parts C, D, and F: if currently receiving gemcitabine or pemetrexed (single-agent or in combination with another therapy), a participant may continue to receive 1 of these 2 therapies provided that extracranial disease is stable for at least 6 weeks and CNS disease progression has occurred while on this therapy.",
            "criterions": [
                {
                    "exact_snippets": "NSCLC participants",
                    "criterion": "NSCLC",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "currently receiving gemcitabine or pemetrexed",
                    "criterion": "gemcitabine or pemetrexed therapy",
                    "requirements": [
                        {
                            "requirement_type": "current treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "extracranial disease is stable for at least 6 weeks",
                    "criterion": "extracranial disease stability",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "CNS disease progression has occurred while on this therapy",
                    "criterion": "CNS disease progression",
                    "requirements": [
                        {
                            "requirement_type": "progression",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Have adequate organ function.",
            "criterions": [
                {
                    "exact_snippets": "adequate organ function",
                    "criterion": "organ function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "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 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": "* Require immediate local therapy, including but not limited to WBRT, SRS, or surgical resection, for treatment of brain metastases.",
            "criterions": [
                {
                    "exact_snippets": "Require immediate local therapy, including but not limited to WBRT, SRS, or surgical resection, for treatment of brain metastases.",
                    "criterion": "brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "treatment necessity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Are taking concurrent enzyme-inducing antiepileptic drugs (EIAED).",
            "criterions": [
                {
                    "exact_snippets": "Are taking concurrent enzyme-inducing antiepileptic drugs (EIAED)",
                    "criterion": "enzyme-inducing antiepileptic drugs (EIAED)",
                    "requirements": [
                        {
                            "requirement_type": "concurrent use",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Have evidence of significant (ie, symptomatic) intracranial hemorrhage.",
            "criterions": [
                {
                    "exact_snippets": "evidence of significant (ie, symptomatic) intracranial hemorrhage",
                    "criterion": "intracranial hemorrhage",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "severity",
                            "expected_value": "significant"
                        },
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* For Parts A, B, C, D, E: Have evidence of leptomeningeal metastases. Note: discrete dural metastases are permitted.",
            "criterions": [
                {
                    "exact_snippets": "evidence of leptomeningeal metastases",
                    "criterion": "leptomeningeal metastases",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Have experienced >2 seizures within 4 weeks prior to study entry.",
            "criterions": [
                {
                    "exact_snippets": "Have experienced >2 seizures within 4 weeks prior to study entry.",
                    "criterion": "seizures",
                    "requirements": [
                        {
                            "requirement_type": "frequency",
                            "expected_value": {
                                "operator": ">",
                                "value": 2,
                                "unit": "seizures"
                            }
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 4 weeks prior to study entry"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* For Parts A, B, D, E, and F: Have previously received treatment with any cyclin dependent kinase 6 (CDK6) inhibitor. For Part C participants may have received prior palbociclib or ribociclib, but not abemaciclib treatment.",
            "criterions": [
                {
                    "exact_snippets": "previously received treatment with any cyclin dependent kinase 6 (CDK6) inhibitor",
                    "criterion": "CDK6 inhibitor treatment",
                    "requirements": [
                        {
                            "requirement_type": "prior treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Part C participants may have received prior palbociclib or ribociclib, but not abemaciclib treatment",
                    "criterion": "palbociclib or ribociclib treatment",
                    "requirements": [
                        {
                            "requirement_type": "prior treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Part C participants may have received prior palbociclib or ribociclib, but not abemaciclib treatment",
                    "criterion": "abemaciclib treatment",
                    "requirements": [
                        {
                            "requirement_type": "prior treatment",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Have known contraindication to Gd-MRI.",
            "criterions": [
                {
                    "exact_snippets": "known contraindication to Gd-MRI",
                    "criterion": "Gd-MRI contraindication",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Have a preexisting chronic condition resulting in persistent diarrhea.",
            "criterions": [
                {
                    "exact_snippets": "preexisting chronic condition resulting in persistent diarrhea",
                    "criterion": "chronic condition",
                    "requirements": [
                        {
                            "requirement_type": "resulting in",
                            "expected_value": "persistent diarrhea"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}