{
    "info": {
        "nct_id": "NCT00732420",
        "official_title": "A Phase I Open-label Study of the Safety, Tolerability, and Pharmacokinetics of Two Schedules of Oral Topotecan in Combination With Pazopanib in Subjects With Advanced Solid Tumors",
        "inclusion_criteria": "Healthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "",
        "miscellaneous_criteria": "Inclusion Criteria -\n\n* signed, written informed consent.\n* at least 18 years of age.\n* ECOG performance status 0 or 1.\n* Subjects must have histologically or cytologically confirmed diagnosis of advanced cancer and a solid tumor malignancy that has relapsed or is refractory to standard therapy or for which there is no established therapy.\n* able to swallow and retain oral medications.\n* females are eligible to enter and participate in this study providing adequate established contraception is being practiced.\n\nExclusion Criteria\n\n* had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C)\n* received an investigational drug within 30 days or 5 half-lives (whichever is longer).\n* received prior treatment with pazopanib/investigational anti-angiogenic compounds.\n* presence of uncontrolled infection.\n* pregnant or lactating.\n* poorly controlled hypertension (SBP of ? 140 mmHg, or DBP of ? 90 mmHg.\n* Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.-\n* arterial thrombi, myocardial infarction, admission for unstable angina, uncontrolled or symptomatic arrhythmia, cardiac angioplasty, or stenting within the last 6 months.\n* any unresolved bowel obstruction or diarrhea ? Grade 1.\n* received an allogeneic bone marrow transplant.\n* known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or topotecan.\n* any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance with the study.\n* psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.\n* clinical history, current alcohol or illicit drug use which, in the judgment of the investigator, would interfere with the subject's ability to comply with the dosing schedule and protocol-specified evaluations."
    },
    "inclusion_lines": [
        {
            "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": [],
    "miscellaneous_lines": [
        {
            "line": "* signed, written informed consent.",
            "criterions": [
                {
                    "exact_snippets": "signed, written informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "signed",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "written",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* at least 18 years of age.",
            "criterions": [
                {
                    "exact_snippets": "at least 18 years of age",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* ECOG performance status 0 or 1.",
            "criterions": [
                {
                    "exact_snippets": "ECOG performance status 0 or 1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Subjects must have histologically or cytologically confirmed diagnosis of advanced cancer and a solid tumor malignancy that has relapsed or is refractory to standard therapy or for which there is no established therapy.",
            "criterions": [
                {
                    "exact_snippets": "histologically or cytologically confirmed diagnosis of advanced cancer",
                    "criterion": "advanced cancer diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "solid tumor malignancy",
                    "criterion": "solid tumor malignancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "relapsed or is refractory to standard therapy",
                    "criterion": "response to standard therapy",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "relapsed",
                                "refractory"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "no established therapy",
                    "criterion": "availability of established therapy",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* able to swallow and retain oral medications.",
            "criterions": [
                {
                    "exact_snippets": "able to swallow",
                    "criterion": "ability to swallow",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "retain oral medications",
                    "criterion": "ability to retain oral medications",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* females are eligible to enter and participate in this study providing adequate established contraception is being practiced.",
            "criterions": [
                {
                    "exact_snippets": "females are eligible",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected value",
                            "expected_value": "female"
                        }
                    ]
                },
                {
                    "exact_snippets": "adequate established contraception is being practiced",
                    "criterion": "contraception",
                    "requirements": [
                        {
                            "requirement_type": "practice",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C)",
            "criterions": [
                {
                    "exact_snippets": "had chemotherapy or radiotherapy within 4 weeks",
                    "criterion": "chemotherapy or radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "6 weeks for nitrosoureas or mitomycin C",
                    "criterion": "nitrosoureas or mitomycin C",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 6,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* received an investigational drug within 30 days or 5 half-lives (whichever is longer).",
            "criterions": [
                {
                    "exact_snippets": "received an investigational drug within 30 days or 5 half-lives (whichever is longer)",
                    "criterion": "investigational drug",
                    "requirements": [
                        {
                            "requirement_type": "time since last dose",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 30,
                                        "unit": "days"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "time since last dose",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "half-lives"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* received prior treatment with pazopanib/investigational anti-angiogenic compounds.",
            "criterions": [
                {
                    "exact_snippets": "received prior treatment with pazopanib",
                    "criterion": "prior treatment with pazopanib",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "received prior treatment with ... investigational anti-angiogenic compounds",
                    "criterion": "prior treatment with investigational anti-angiogenic compounds",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* presence of uncontrolled infection.",
            "criterions": [
                {
                    "exact_snippets": "presence of uncontrolled infection",
                    "criterion": "infection",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* pregnant or lactating.",
            "criterions": [
                {
                    "exact_snippets": "pregnant",
                    "criterion": "pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "lactating",
                    "criterion": "lactation status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* poorly controlled hypertension (SBP of ? 140 mmHg, or DBP of ? 90 mmHg.",
            "criterions": [
                {
                    "exact_snippets": "poorly controlled hypertension (SBP of ? 140 mmHg",
                    "criterion": "systolic blood pressure (SBP)",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 140,
                                "unit": "mmHg"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "poorly controlled hypertension ... DBP of ? 90 mmHg",
                    "criterion": "diastolic blood pressure (DBP)",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 90,
                                "unit": "mmHg"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.-",
            "criterions": [
                {
                    "exact_snippets": "Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system",
                    "criterion": "heart failure",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "Class III",
                                "Class IV"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* arterial thrombi, myocardial infarction, admission for unstable angina, uncontrolled or symptomatic arrhythmia, cardiac angioplasty, or stenting within the last 6 months.",
            "criterions": [
                {
                    "exact_snippets": "arterial thrombi",
                    "criterion": "arterial thrombi",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "myocardial infarction",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "occurrence",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "admission for unstable angina",
                    "criterion": "admission for unstable angina",
                    "requirements": [
                        {
                            "requirement_type": "occurrence",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled or symptomatic arrhythmia",
                    "criterion": "uncontrolled or symptomatic arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "cardiac angioplasty",
                    "criterion": "cardiac angioplasty",
                    "requirements": [
                        {
                            "requirement_type": "occurrence",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "stenting within the last 6 months",
                    "criterion": "stenting",
                    "requirements": [
                        {
                            "requirement_type": "occurrence",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* any unresolved bowel obstruction or diarrhea ? Grade 1.",
            "criterions": [
                {
                    "exact_snippets": "unresolved bowel obstruction",
                    "criterion": "bowel obstruction",
                    "requirements": [
                        {
                            "requirement_type": "resolution",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "unresolved ... diarrhea",
                    "criterion": "diarrhea",
                    "requirements": [
                        {
                            "requirement_type": "resolution",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "diarrhea ? Grade 1",
                    "criterion": "diarrhea",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "Grade 1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* received an allogeneic bone marrow transplant.",
            "criterions": [
                {
                    "exact_snippets": "received an allogeneic bone marrow transplant",
                    "criterion": "allogeneic bone marrow transplant",
                    "requirements": [
                        {
                            "requirement_type": "received",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or topotecan.",
            "criterions": [
                {
                    "exact_snippets": "known immediate or delayed hypersensitivity reaction ... to drugs chemically related to pazopanib",
                    "criterion": "hypersensitivity reaction to drugs related to pazopanib",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "known immediate or delayed hypersensitivity reaction ... to drugs chemically related to ... topotecan",
                    "criterion": "hypersensitivity reaction to drugs related to topotecan",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance with the study.",
            "criterions": [
                {
                    "exact_snippets": "serious and/or unstable pre-existing medical ... conditions",
                    "criterion": "pre-existing medical conditions",
                    "requirements": [
                        {
                            "requirement_type": "severity/stability",
                            "expected_value": "serious and/or unstable"
                        }
                    ]
                },
                {
                    "exact_snippets": "serious and/or unstable pre-existing ... psychiatric ... conditions",
                    "criterion": "pre-existing psychiatric conditions",
                    "requirements": [
                        {
                            "requirement_type": "severity/stability",
                            "expected_value": "serious and/or unstable"
                        }
                    ]
                },
                {
                    "exact_snippets": "serious and/or unstable pre-existing ... other conditions",
                    "criterion": "pre-existing other conditions",
                    "requirements": [
                        {
                            "requirement_type": "severity/stability",
                            "expected_value": "serious and/or unstable"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.",
            "criterions": [
                {
                    "exact_snippets": "psychological ... conditions that do not permit compliance with the protocol",
                    "criterion": "psychological conditions",
                    "requirements": [
                        {
                            "requirement_type": "compliance",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "familial ... conditions that do not permit compliance with the protocol",
                    "criterion": "familial conditions",
                    "requirements": [
                        {
                            "requirement_type": "compliance",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "sociological ... conditions that do not permit compliance with the protocol",
                    "criterion": "sociological conditions",
                    "requirements": [
                        {
                            "requirement_type": "compliance",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "geographical conditions that do not permit compliance with the protocol",
                    "criterion": "geographical conditions",
                    "requirements": [
                        {
                            "requirement_type": "compliance",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* clinical history, current alcohol or illicit drug use which, in the judgment of the investigator, would interfere with the subject's ability to comply with the dosing schedule and protocol-specified evaluations.",
            "criterions": [
                {
                    "exact_snippets": "clinical history",
                    "criterion": "clinical history",
                    "requirements": [
                        {
                            "requirement_type": "interference with compliance",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "current alcohol or illicit drug use",
                    "criterion": "current alcohol or illicit drug use",
                    "requirements": [
                        {
                            "requirement_type": "interference with compliance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": [
        {
            "line": "Inclusion Criteria -",
            "criterions": []
        },
        {
            "line": "Exclusion Criteria",
            "criterions": []
        }
    ]
}