{
    "info": {
        "nct_id": "NCT00121680",
        "official_title": "A Phase I/Ib, Multicenter, Open-Label, Dose Escalation Study of E7080 in Patients With Solid Tumors and in Combination With Temozolomide in Patients With Advanced and/or Metastatic Melanoma",
        "inclusion_criteria": "Patients with a histologically and/or cytologically confirmed solid tumor or lymphoma who are resistant/refractory to approved therapies or for whom no curative therapies are available All previous treatment (including surgery and radiotherapy) must have been completed at least four weeks prior to study entry and any acute toxicities must have resolved Aged 18 years. Because of the potential additional risk to children suggested by preclinical models of dysplasia in growing epiphyseal growth plates, enrollment will be limited to adult patients ECOG performance status score of 0 or 1 Written informed consent prior to any study specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice Willing and able to comply with the protocol guidelines for the duration of the study For patients in the Schedule 2 Expanded Melanoma Cohort only: histologically and/or cytologically confirmed advanced and/or metastatic melanoma who are resistant/refractory to approved therapies or for whom no curative therapies are available. In addition, patients must have melanoma lesions amenable to tissue biopsy and must agree to undergo biopsies of malignant and adjacent non-malignant tissue pretreatment and at the end of Cycle 1 of treatment For patients in the Melanoma Combination Cohort only: histologically and/or cytologically confirmed melanoma that is advanced and/or metastatic\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "Untreated or unstable metastases to the central nervous system (CNS) tumors. Patients who have completed local therapy and have discontinued the use of steroids for this indication at least 4 weeks prior to commencing treatment and in whom stability has been proven by at least 2 CT or MRI scans obtained at least 4 weeks apart are permitted Any of the following laboratory parameters: hemoglobin < 9 g/dL (5.6 mmol/L); neutrophils <1.5 x 109/L; platelets <100 x 109/L; serum bilirubin >25 mol/L (1.5 mg/dL); liver function tests with values >3 x upper limit of normal (ULN); renal function with serum creatinine >1.5 ULN or creatinine clearance < 60 mL/min Positive history of HIV, active hepatitis B or active hepatitis C or severe/uncontrolled intercurrent illness or infection Patients with centrally located non-small cell lung cancers and squamous cell lung cancers Clinically significant cardiac impairment or unstable ischemic heart disease including a myocardial infarction within six months of study start Patients with marked Baseline prolongation of QT/QTc interval (QTc interval > 450 msec for males or > 470 msec for females) using the Fridericia method for QTc analysis Bleeding or thrombotic disorders, or using therapeutic dosages of anticoagulants, such as warfarin. Occasional use of NSAIDs and antiplatelet agents such as aspirin, clopidogrel, aggrenox and dipyridamole are not considered exclusionary if taken <7 days per 28 days. However, if the patient requires chronic use (>/=7 days out of 28 days) of full doses of aspirin or NSAIDs then the patient is excluded. Concomitant antiplatelet agents and NSAIDs should be used with caution Requirement for chronic use of full dose aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) Poorly controlled hypertension (defined as requiring changes in any hypertensive regimen within 1 week three months of study entry) or patients diagnosed with hypertension based on repeat blood pressure measurements of >160/90 mmHg at Screening >1+ proteinuria on urine dipstick testing or 30 mg/dL A history of gastrointestinal malabsorption or having undergone surgery requiring gastrointestinal anastomoses within four weeks of starting therapy or who have not recovered from major surgery within three weeks of starting therapy History of alcoholism, drug addiction, or any psychiatric or psychological condition which, in the opinion of the Investigator, would impair study compliance Any treatment with investigational drugs within 30 days before the start of the study Previous treatment with E7080 Known intolerance to temozolomide (or any of the excipients) Women who are pregnant or breast-feeding; women of childbearing potential with a positive pregnancy test at Screening or no pregnancy test. Women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception (including two forms of contraception, one of which must be a barrier method) in the opinion of the Investigator (revised per Amendment 04). Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential Fertile males with female partners who are not willing to use contraception or whose female partners are not using adequate contraceptive protection Legal incapacity",
        "miscellaneous_criteria": ""
    },
    "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": [
        {
            "line": "Untreated or unstable metastases to the central nervous system (CNS) tumors. Patients who have completed local therapy and have discontinued the use of steroids for this indication at least 4 weeks prior to commencing treatment and in whom stability has been proven by at least 2 CT or MRI scans obtained at least 4 weeks apart are permitted Any of the following laboratory parameters: hemoglobin < 9 g/dL (5.6 mmol/L); neutrophils <1.5 x 109/L; platelets <100 x 109/L; serum bilirubin >25 mol/L (1.5 mg/dL); liver function tests with values >3 x upper limit of normal (ULN); renal function with serum creatinine >1.5 ULN or creatinine clearance < 60 mL/min Positive history of HIV, active hepatitis B or active hepatitis C or severe/uncontrolled intercurrent illness or infection Patients with centrally located non-small cell lung cancers and squamous cell lung cancers Clinically significant cardiac impairment or unstable ischemic heart disease including a myocardial infarction within six months of study start Patients with marked Baseline prolongation of QT/QTc interval (QTc interval > 450 msec for males or > 470 msec for females) using the Fridericia method for QTc analysis Bleeding or thrombotic disorders, or using therapeutic dosages of anticoagulants, such as warfarin. Occasional use of NSAIDs and antiplatelet agents such as aspirin, clopidogrel, aggrenox and dipyridamole are not considered exclusionary if taken <7 days per 28 days. However, if the patient requires chronic use (>/=7 days out of 28 days) of full doses of aspirin or NSAIDs then the patient is excluded. Concomitant antiplatelet agents and NSAIDs should be used with caution Requirement for chronic use of full dose aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) Poorly controlled hypertension (defined as requiring changes in any hypertensive regimen within 1 week three months of study entry) or patients diagnosed with hypertension based on repeat blood pressure measurements of >160/90 mmHg at Screening >1+ proteinuria on urine dipstick testing or 30 mg/dL A history of gastrointestinal malabsorption or having undergone surgery requiring gastrointestinal anastomoses within four weeks of starting therapy or who have not recovered from major surgery within three weeks of starting therapy History of alcoholism, drug addiction, or any psychiatric or psychological condition which, in the opinion of the Investigator, would impair study compliance Any treatment with investigational drugs within 30 days before the start of the study Previous treatment with E7080 Known intolerance to temozolomide (or any of the excipients) Women who are pregnant or breast-feeding; women of childbearing potential with a positive pregnancy test at Screening or no pregnancy test. Women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception (including two forms of contraception, one of which must be a barrier method) in the opinion of the Investigator (revised per Amendment 04). Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential Fertile males with female partners who are not willing to use contraception or whose female partners are not using adequate contraceptive protection Legal incapacity",
            "criterions": [
                {
                    "exact_snippets": "Untreated or unstable metastases to the central nervous system (CNS) tumors",
                    "criterion": "metastases to the CNS",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "untreated or unstable"
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients who have completed local therapy and have discontinued the use of steroids for this indication at least 4 weeks prior to commencing treatment and in whom stability has been proven by at least 2 CT or MRI scans obtained at least 4 weeks apart are permitted",
                    "criterion": "CNS metastases stability",
                    "requirements": [
                        {
                            "requirement_type": "local therapy completion",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "steroid discontinuation",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        },
                        {
                            "requirement_type": "stability proven by CT or MRI",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "hemoglobin < 9 g/dL (5.6 mmol/L)",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 9,
                                "unit": "g/dL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "neutrophils <1.5 x 109/L",
                    "criterion": "neutrophil count",
                    "requirements": [
                        {
                            "requirement_type": "count",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "x 10^9/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "platelets <100 x 109/L",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "count",
                            "expected_value": {
                                "operator": "<",
                                "value": 100,
                                "unit": "x 10^9/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "serum bilirubin >25 mol/L (1.5 mg/dL)",
                    "criterion": "serum bilirubin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 25,
                                "unit": "mol/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "liver function tests with values >3 x upper limit of normal (ULN)",
                    "criterion": "liver function tests",
                    "requirements": [
                        {
                            "requirement_type": "values",
                            "expected_value": {
                                "operator": ">",
                                "value": 3,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "renal function with serum creatinine >1.5 ULN or creatinine clearance < 60 mL/min",
                    "criterion": "renal function",
                    "requirements": [
                        {
                            "requirement_type": "serum creatinine",
                            "expected_value": {
                                "operator": ">",
                                "value": 1.5,
                                "unit": "ULN"
                            }
                        },
                        {
                            "requirement_type": "creatinine clearance",
                            "expected_value": {
                                "operator": "<",
                                "value": 60,
                                "unit": "mL/min"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Positive history of HIV, active hepatitis B or active hepatitis C",
                    "criterion": "viral infections",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": [
                                "HIV",
                                "active hepatitis B",
                                "active hepatitis C"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "severe/uncontrolled intercurrent illness or infection",
                    "criterion": "intercurrent illness or infection",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe/uncontrolled"
                        }
                    ]
                },
                {
                    "exact_snippets": "centrally located non-small cell lung cancers and squamous cell lung cancers",
                    "criterion": "lung cancer type",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "centrally located non-small cell lung cancer",
                                "squamous cell lung cancer"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Clinically significant cardiac impairment or unstable ischemic heart disease including a myocardial infarction within six months of study start",
                    "criterion": "cardiac condition",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": [
                                "clinically significant cardiac impairment",
                                "unstable ischemic heart disease",
                                "myocardial infarction within six months"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "marked Baseline prolongation of QT/QTc interval (QTc interval > 450 msec for males or > 470 msec for females) using the Fridericia method for QTc analysis",
                    "criterion": "QT/QTc interval prolongation",
                    "requirements": [
                        {
                            "requirement_type": "QTc interval",
                            "expected_value": {
                                "operator": ">",
                                "value": 450,
                                "unit": "msec"
                            }
                        },
                        {
                            "requirement_type": "QTc interval",
                            "expected_value": {
                                "operator": ">",
                                "value": 470,
                                "unit": "msec"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Bleeding or thrombotic disorders, or using therapeutic dosages of anticoagulants, such as warfarin",
                    "criterion": "bleeding or thrombotic disorders",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Requirement for chronic use of full dose aspirin or non-steroidal anti-inflammatory drugs (NSAIDs)",
                    "criterion": "chronic use of aspirin or NSAIDs",
                    "requirements": [
                        {
                            "requirement_type": "use",
                            "expected_value": "chronic"
                        }
                    ]
                },
                {
                    "exact_snippets": "Poorly controlled hypertension (defined as requiring changes in any hypertensive regimen within 1 week three months of study entry) or patients diagnosed with hypertension based on repeat blood pressure measurements of >160/90 mmHg at Screening",
                    "criterion": "hypertension control",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "poorly controlled"
                        }
                    ]
                },
                {
                    "exact_snippets": ">1+ proteinuria on urine dipstick testing or 30 mg/dL",
                    "criterion": "proteinuria",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": ">1+ or 30 mg/dL"
                        }
                    ]
                },
                {
                    "exact_snippets": "history of gastrointestinal malabsorption or having undergone surgery requiring gastrointestinal anastomoses within four weeks of starting therapy or who have not recovered from major surgery within three weeks of starting therapy",
                    "criterion": "gastrointestinal condition",
                    "requirements": [
                        {
                            "requirement_type": "history or surgery",
                            "expected_value": [
                                "gastrointestinal malabsorption",
                                "gastrointestinal anastomoses within four weeks",
                                "not recovered from major surgery within three weeks"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "History of alcoholism, drug addiction, or any psychiatric or psychological condition which, in the opinion of the Investigator, would impair study compliance",
                    "criterion": "substance abuse or psychiatric condition",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": [
                                "alcoholism",
                                "drug addiction",
                                "psychiatric or psychological condition"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Any treatment with investigational drugs within 30 days before the start of the study",
                    "criterion": "investigational drug treatment",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "within 30 days"
                        }
                    ]
                },
                {
                    "exact_snippets": "Previous treatment with E7080",
                    "criterion": "previous treatment with E7080",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Known intolerance to temozolomide (or any of the excipients)",
                    "criterion": "intolerance to temozolomide",
                    "requirements": [
                        {
                            "requirement_type": "intolerance",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Women who are pregnant or breast-feeding; women of childbearing potential with a positive pregnancy test at Screening or no pregnancy test",
                    "criterion": "pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "pregnant",
                                "breast-feeding",
                                "positive pregnancy test",
                                "no pregnancy test"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception (including two forms of contraception, one of which must be a barrier method) in the opinion of the Investigator (revised per Amendment 04)",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "use",
                            "expected_value": "adequate measures of contraception"
                        }
                    ]
                },
                {
                    "exact_snippets": "Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential",
                    "criterion": "perimenopausal status",
                    "requirements": [
                        {
                            "requirement_type": "amenorrhea duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Fertile males with female partners who are not willing to use contraception or whose female partners are not using adequate contraceptive protection",
                    "criterion": "contraception use by male partners",
                    "requirements": [
                        {
                            "requirement_type": "use",
                            "expected_value": "adequate contraceptive protection"
                        }
                    ]
                },
                {
                    "exact_snippets": "Legal incapacity",
                    "criterion": "legal capacity",
                    "requirements": [
                        {
                            "requirement_type": "capacity",
                            "expected_value": "legal incapacity"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "Patients with a histologically and/or cytologically confirmed solid tumor or lymphoma who are resistant/refractory to approved therapies or for whom no curative therapies are available All previous treatment (including surgery and radiotherapy) must have been completed at least four weeks prior to study entry and any acute toxicities must have resolved Aged 18 years. Because of the potential additional risk to children suggested by preclinical models of dysplasia in growing epiphyseal growth plates, enrollment will be limited to adult patients ECOG performance status score of 0 or 1 Written informed consent prior to any study specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice Willing and able to comply with the protocol guidelines for the duration of the study For patients in the Schedule 2 Expanded Melanoma Cohort only: histologically and/or cytologically confirmed advanced and/or metastatic melanoma who are resistant/refractory to approved therapies or for whom no curative therapies are available. In addition, patients must have melanoma lesions amenable to tissue biopsy and must agree to undergo biopsies of malignant and adjacent non-malignant tissue pretreatment and at the end of Cycle 1 of treatment For patients in the Melanoma Combination Cohort only: histologically and/or cytologically confirmed melanoma that is advanced and/or metastatic",
            "criterions": [
                {
                    "exact_snippets": "histologically and/or cytologically confirmed solid tumor or lymphoma",
                    "criterion": "solid tumor or lymphoma",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "histologically and/or cytologically"
                        }
                    ]
                },
                {
                    "exact_snippets": "resistant/refractory to approved therapies or for whom no curative therapies are available",
                    "criterion": "resistance/refractoriness to approved therapies",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "resistant/refractory"
                        }
                    ]
                },
                {
                    "exact_snippets": "All previous treatment (including surgery and radiotherapy) must have been completed at least four weeks prior to study entry",
                    "criterion": "previous treatment completion",
                    "requirements": [
                        {
                            "requirement_type": "time since completion",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "any acute toxicities must have resolved",
                    "criterion": "acute toxicities",
                    "requirements": [
                        {
                            "requirement_type": "resolution",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Aged 18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "ECOG performance status score of 0 or 1",
                    "criterion": "ECOG performance status score",
                    "requirements": [
                        {
                            "requirement_type": "score",
                            "expected_value": [
                                "0",
                                "1"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Written informed consent prior to any study specific screening procedures",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Willing and able to comply with the protocol guidelines for the duration of the study",
                    "criterion": "compliance with protocol guidelines",
                    "requirements": [
                        {
                            "requirement_type": "willingness and ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Schedule 2 Expanded Melanoma Cohort only: histologically and/or cytologically confirmed advanced and/or metastatic melanoma",
                    "criterion": "advanced and/or metastatic melanoma",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "histologically and/or cytologically"
                        }
                    ]
                },
                {
                    "exact_snippets": "Schedule 2 Expanded Melanoma Cohort only: melanoma lesions amenable to tissue biopsy",
                    "criterion": "melanoma lesions amenable to tissue biopsy",
                    "requirements": [
                        {
                            "requirement_type": "amenability to biopsy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Schedule 2 Expanded Melanoma Cohort only: must agree to undergo biopsies of malignant and adjacent non-malignant tissue pretreatment and at the end of Cycle 1 of treatment",
                    "criterion": "agreement to undergo biopsies",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Melanoma Combination Cohort only: histologically and/or cytologically confirmed melanoma that is advanced and/or metastatic",
                    "criterion": "advanced and/or metastatic melanoma",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "histologically and/or cytologically"
                        }
                    ]
                }
            ]
        }
    ],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}