{
    "info": {
        "nct_id": "NCT00770731",
        "official_title": "A Phase I Study of Temsirolimus, Topotecan, and Bortezomib in Patients With Advanced Malignancy",
        "inclusion_criteria": "1. Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that improves survival by at least three months\n2. Patients should be at least four weeks or 5 half lives from the last day of chemotherapy, and antibody or other biological therapy, whichever is shorter.\n3. Patients should be at least four weeks from the last day of therapeutic radiation.\n4. The Eastern Cooperative Oncology Group (ECOG) performance status </= 2 or Karnofsky >/= 60%.\n5. Patients must have allowable organ and marrow function defined as: Absolute neutrophil count >/= 1,000/mL, Platelets >/=75,000/mL, Serum creatinine </= 2 * Upper Limit of Normal (ULN), Total bilirubin </= 2 * ULN, aminotransferase (ALT or SGPT) </= 3 * ULN, Fasting total cholesterol <= 350 mg/dL and triglyceride level <= 400 mg/dL.\n6. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and will be advised to avoid pregnancy for 3 months after completion of therapy.\n7. Ability to understand and the willingness to sign a written informed consent document.\n8. Patients may not be receiving any other investigational agents and/or any other concurrent anticancer agents or therapies except for continuing on hormonal therapy in cases of prostate cancer.\n9. Treatment on this study may begin within 24 hours after Phase 0 dose of temsirolimus.\nHealthy volunteers allowed",
        "exclusion_criteria": "1. Patients with hemoptysis within 28 days prior to entering the study.\n2. Patients with clinically significant unexplained bleeding within 28 days prior to entering the study.\n3. Patients with clinically significant cardiovascular disease: • History of CVA within 6 months • Myocardial infarction or unstable angina within 6 months • Unstable angina pectoris\n4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on Day 1.\n5. Pregnant or lactating women.\n6. History of hypersensitivity to bortezomib or any component of the bortezomib formulation.\n7. History of hypersensitivity to topotecan or any component of the topotecan formulation.\n8. History of hypersensitivity to temsirolimus or its metabolites (including sirolimus), polysorbate 80, or to any component of the formulation.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that improves survival by at least three months",
            "criterions": [
                {
                    "exact_snippets": "advanced or metastatic cancer",
                    "criterion": "cancer stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "advanced",
                                "metastatic"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "refractory to standard therapy",
                    "criterion": "response to standard therapy",
                    "requirements": [
                        {
                            "requirement_type": "response",
                            "expected_value": "refractory"
                        }
                    ]
                },
                {
                    "exact_snippets": "relapsed after standard therapy",
                    "criterion": "response to standard therapy",
                    "requirements": [
                        {
                            "requirement_type": "response",
                            "expected_value": "relapsed"
                        }
                    ]
                },
                {
                    "exact_snippets": "no standard therapy that improves survival by at least three months",
                    "criterion": "availability of effective standard therapy",
                    "requirements": [
                        {
                            "requirement_type": "effectiveness",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Patients should be at least four weeks or 5 half lives from the last day of chemotherapy, and antibody or other biological therapy, whichever is shorter.",
            "criterions": [
                {
                    "exact_snippets": "Patients should be at least four weeks or 5 half lives from the last day of chemotherapy",
                    "criterion": "time since last chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 4,
                                        "unit": "weeks"
                                    },
                                    {
                                        "operator": ">=",
                                        "value": 5,
                                        "unit": "half lives"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients should be at least four weeks or 5 half lives from the last day of ... antibody or other biological therapy",
                    "criterion": "time since last antibody or biological therapy",
                    "requirements": [
                        {
                            "requirement_type": "time",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 4,
                                        "unit": "weeks"
                                    },
                                    {
                                        "operator": ">=",
                                        "value": 5,
                                        "unit": "half lives"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patients should be at least four weeks from the last day of therapeutic radiation.",
            "criterions": [
                {
                    "exact_snippets": "Patients should be at least four weeks from the last day of therapeutic radiation.",
                    "criterion": "time since last therapeutic radiation",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. The Eastern Cooperative Oncology Group (ECOG) performance status </= 2 or Karnofsky >/= 60%.",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status </= 2",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Karnofsky >/= 60%",
                    "criterion": "Karnofsky performance status",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 60,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Patients must have allowable organ and marrow function defined as: Absolute neutrophil count >/= 1,000/mL, Platelets >/=75,000/mL, Serum creatinine </= 2 * Upper Limit of Normal (ULN), Total bilirubin </= 2 * ULN, aminotransferase (ALT or SGPT) </= 3 * ULN, Fasting total cholesterol <= 350 mg/dL and triglyceride level <= 400 mg/dL.",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count >/= 1,000/mL",
                    "criterion": "absolute neutrophil count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1000,
                                "unit": "mL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Platelets >/=75,000/mL",
                    "criterion": "platelets",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 75000,
                                "unit": "mL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Serum creatinine </= 2 * Upper Limit of Normal (ULN)",
                    "criterion": "serum creatinine",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": "<= 2 * ULN"
                        }
                    ]
                },
                {
                    "exact_snippets": "Total bilirubin </= 2 * ULN",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": "<= 2 * ULN"
                        }
                    ]
                },
                {
                    "exact_snippets": "aminotransferase (ALT or SGPT) </= 3 * ULN",
                    "criterion": "aminotransferase (ALT or SGPT)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": "<= 3 * ULN"
                        }
                    ]
                },
                {
                    "exact_snippets": "Fasting total cholesterol <= 350 mg/dL",
                    "criterion": "fasting total cholesterol",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 350,
                                "unit": "mg/dL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "triglyceride level <= 400 mg/dL",
                    "criterion": "triglyceride level",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 400,
                                "unit": "mg/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and will be advised to avoid pregnancy for 3 months after completion of therapy.",
            "criterions": [
                {
                    "exact_snippets": "Women of child-bearing potential",
                    "criterion": "women of child-bearing potential",
                    "requirements": [
                        {
                            "requirement_type": "agreement to use contraception",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "men must agree to use adequate contraception",
                    "criterion": "men",
                    "requirements": [
                        {
                            "requirement_type": "agreement to use contraception",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence)",
                    "criterion": "contraception method",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "hormonal",
                                "barrier method of birth control",
                                "abstinence"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "must agree to use adequate contraception ... prior to study entry and for the duration of study participation",
                    "criterion": "contraception duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "prior to study entry and for the duration of study participation"
                        }
                    ]
                },
                {
                    "exact_snippets": "will be advised to avoid pregnancy for 3 months after completion of therapy",
                    "criterion": "pregnancy avoidance",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "3 months after completion of therapy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Ability to understand and the willingness to sign a written informed consent document.",
            "criterions": [
                {
                    "exact_snippets": "Ability to understand",
                    "criterion": "cognitive ability",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "willingness to sign a written informed consent document",
                    "criterion": "willingness to consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Patients may not be receiving any other investigational agents and/or any other concurrent anticancer agents or therapies except for continuing on hormonal therapy in cases of prostate cancer.",
            "criterions": [
                {
                    "exact_snippets": "Patients may not be receiving any other investigational agents",
                    "criterion": "investigational agents",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients may not be receiving ... any other concurrent anticancer agents or therapies",
                    "criterion": "concurrent anticancer agents or therapies",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "except for continuing on hormonal therapy in cases of prostate cancer",
                    "criterion": "hormonal therapy in cases of prostate cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Treatment on this study may begin within 24 hours after Phase 0 dose of temsirolimus.",
            "criterions": [
                {
                    "exact_snippets": "Treatment on this study may begin within 24 hours after Phase 0 dose of temsirolimus.",
                    "criterion": "treatment start time",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 24,
                                "unit": "hours"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. Patients with hemoptysis within 28 days prior to entering the study.",
            "criterions": [
                {
                    "exact_snippets": "hemoptysis within 28 days prior to entering the study",
                    "criterion": "hemoptysis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 28 days prior to entering the study"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Patients with clinically significant unexplained bleeding within 28 days prior to entering the study.",
            "criterions": [
                {
                    "exact_snippets": "clinically significant unexplained bleeding",
                    "criterion": "unexplained bleeding",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "clinically significant"
                        }
                    ]
                },
                {
                    "exact_snippets": "within 28 days prior to entering the study",
                    "criterion": "time since last unexplained bleeding",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patients with clinically significant cardiovascular disease: • History of CVA within 6 months • Myocardial infarction or unstable angina within 6 months • Unstable angina pectoris",
            "criterions": [
                {
                    "exact_snippets": "clinically significant cardiovascular disease",
                    "criterion": "cardiovascular disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "clinically significant"
                        }
                    ]
                },
                {
                    "exact_snippets": "History of CVA within 6 months",
                    "criterion": "cerebrovascular accident (CVA)",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Myocardial infarction or unstable angina within 6 months",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Myocardial infarction or unstable angina within 6 months",
                    "criterion": "unstable angina",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Unstable angina pectoris",
                    "criterion": "unstable angina pectoris",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on Day 1.",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled intercurrent illness",
                    "criterion": "intercurrent illness",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "ongoing or active infection",
                    "criterion": "infection",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "ongoing",
                                "active"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "requiring parenteral antibiotics on Day 1",
                    "criterion": "parenteral antibiotics",
                    "requirements": [
                        {
                            "requirement_type": "requirement",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "timing",
                            "expected_value": "Day 1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Pregnant or lactating women.",
            "criterions": [
                {
                    "exact_snippets": "Pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "lactating women",
                    "criterion": "lactation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. History of hypersensitivity to bortezomib or any component of the bortezomib formulation.",
            "criterions": [
                {
                    "exact_snippets": "History of hypersensitivity to bortezomib",
                    "criterion": "hypersensitivity to bortezomib",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "hypersensitivity to ... any component of the bortezomib formulation",
                    "criterion": "hypersensitivity to any component of the bortezomib formulation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. History of hypersensitivity to topotecan or any component of the topotecan formulation.",
            "criterions": [
                {
                    "exact_snippets": "History of hypersensitivity to topotecan",
                    "criterion": "hypersensitivity to topotecan",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "hypersensitivity to ... any component of the topotecan formulation",
                    "criterion": "hypersensitivity to any component of the topotecan formulation",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. History of hypersensitivity to temsirolimus or its metabolites (including sirolimus), polysorbate 80, or to any component of the formulation.",
            "criterions": [
                {
                    "exact_snippets": "History of hypersensitivity to temsirolimus or its metabolites (including sirolimus)",
                    "criterion": "hypersensitivity to temsirolimus or its metabolites",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "hypersensitivity to ... polysorbate 80",
                    "criterion": "hypersensitivity to polysorbate 80",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "hypersensitivity ... to any component of the formulation",
                    "criterion": "hypersensitivity to any component of the formulation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}