{
    "info": {
        "nct_id": "NCT02446431",
        "official_title": "Metronomic Therapy for Pediatric Patients With Solid Tumors at High Risk of Recurrence: A Multi-Institutional Study",
        "inclusion_criteria": "1. The following solid tumors will be studied: rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, other soft tissue sarcomas\n2. Other solid tumors fulfilling the remainder of eligibility criteria and available historical data to determine time to tumor progression\n3. Expected time to progression of < 2 years, based on historical data\n4. All patients will have completed front-line therapy\n5. All patients will be in remission from their primary diagnosis\n6. All patients will start metronomic therapy within 6 weeks of completion of front-line treatment\n7. All patient will have recovered from previous toxicities\n8. All patients or their parents/legal guardian will have signed an informed consent document\n9. All institutional eligibility criteria will be meet\n10. Age: Patients must be ≥ 12 months and <31 years of age at the time of study entry\n11. Patients must have had histologic verification of malignancy at original diagnosis\n12. Patients must have a Lansky or Karnofsky performance status score of ≥ 50, corresponding to ECOG categories 0, 1 or 2.\n13. Adequate renal function defined as: Normal serum creatinine\n14. Normal liver tests (ALT/AST/total bilirubin/triglycerides/cholesterol)\n15. Recovered from all surgical procedures for at least 7 days (minor procedures) or 28 days (major procedures)\n16. Adequate cardiac function defined as: Shortening fraction of ≥ 27% by echocardiogram, or ejection fraction of ≥ 50% by radionuclide angiogram\n17. Platelet count 100,000K/uL (transfusion independent), hemoglobin 8.0 g/dL\n18. Adequate bone marrow function: Peripheral absolute neutrophil count (ANC) 1,000K/uL\n19. Signed Informed Consent document and/or Assent document\nHealthy volunteers allowed\nMust have minimum age of 12 Months\nMust have maximum age of 31 Years",
        "exclusion_criteria": "1. Female patients who are pregnant\n2. Lactating females are not eligible unless they have agreed to discontinue breastfeeding\n3. Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained\n4. Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of study participation\n5. Any primary central nervous system tumor\n6. Any patient who has experienced relapsed or refractory disease or a second malignancy.\n7. Any patient not in remission",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. The following solid tumors will be studied: rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, other soft tissue sarcomas",
            "criterions": [
                {
                    "exact_snippets": "solid tumors ... rhabdomyosarcoma",
                    "criterion": "solid tumor type",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": "rhabdomyosarcoma"
                        }
                    ]
                },
                {
                    "exact_snippets": "solid tumors ... osteosarcoma",
                    "criterion": "solid tumor type",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": "osteosarcoma"
                        }
                    ]
                },
                {
                    "exact_snippets": "solid tumors ... Ewing sarcoma",
                    "criterion": "solid tumor type",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": "Ewing sarcoma"
                        }
                    ]
                },
                {
                    "exact_snippets": "solid tumors ... other soft tissue sarcomas",
                    "criterion": "solid tumor type",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": "other soft tissue sarcomas"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Other solid tumors fulfilling the remainder of eligibility criteria and available historical data to determine time to tumor progression",
            "criterions": [
                {
                    "exact_snippets": "Other solid tumors",
                    "criterion": "solid tumors",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": "solid"
                        }
                    ]
                },
                {
                    "exact_snippets": "available historical data",
                    "criterion": "historical data",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "determine time to tumor progression",
                    "criterion": "time to tumor progression",
                    "requirements": [
                        {
                            "requirement_type": "determinability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Expected time to progression of < 2 years, based on historical data",
            "criterions": [
                {
                    "exact_snippets": "Expected time to progression of < 2 years",
                    "criterion": "time to progression",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<",
                                "value": 2,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. All patients will have completed front-line therapy",
            "criterions": [
                {
                    "exact_snippets": "completed front-line therapy",
                    "criterion": "front-line therapy",
                    "requirements": [
                        {
                            "requirement_type": "completion",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. All patients will be in remission from their primary diagnosis",
            "criterions": [
                {
                    "exact_snippets": "patients will be in remission from their primary diagnosis",
                    "criterion": "remission",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "remission"
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. All patients will start metronomic therapy within 6 weeks of completion of front-line treatment",
            "criterions": [
                {
                    "exact_snippets": "start metronomic therapy within 6 weeks of completion of front-line treatment",
                    "criterion": "metronomic therapy start time",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. All patient will have recovered from previous toxicities",
            "criterions": [
                {
                    "exact_snippets": "recovered from previous toxicities",
                    "criterion": "previous toxicities",
                    "requirements": [
                        {
                            "requirement_type": "recovery",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. All patients or their parents/legal guardian will have signed an informed consent document",
            "criterions": [
                {
                    "exact_snippets": "All patients or their parents/legal guardian will have signed an informed consent document",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "signed",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. All institutional eligibility criteria will be meet",
            "criterions": [
                {
                    "exact_snippets": "All institutional eligibility criteria",
                    "criterion": "institutional eligibility criteria",
                    "requirements": [
                        {
                            "requirement_type": "compliance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Age: Patients must be ≥ 12 months and <31 years of age at the time of study entry",
            "criterions": [
                {
                    "exact_snippets": "Age: Patients must be ≥ 12 months and <31 years of age",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 12,
                                        "unit": "months"
                                    },
                                    {
                                        "operator": "<",
                                        "value": 31,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Patients must have had histologic verification of malignancy at original diagnosis",
            "criterions": [
                {
                    "exact_snippets": "histologic verification of malignancy",
                    "criterion": "malignancy verification",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "histologic"
                        }
                    ]
                },
                {
                    "exact_snippets": "original diagnosis",
                    "criterion": "diagnosis timing",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "original"
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Patients must have a Lansky or Karnofsky performance status score of ≥ 50, corresponding to ECOG categories 0, 1 or 2.",
            "criterions": [
                {
                    "exact_snippets": "Lansky or Karnofsky performance status score of ≥ 50",
                    "criterion": "Lansky or Karnofsky performance status score",
                    "requirements": [
                        {
                            "requirement_type": "score",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "corresponding to ECOG categories 0, 1 or 2",
                    "criterion": "ECOG categories",
                    "requirements": [
                        {
                            "requirement_type": "category",
                            "expected_value": [
                                "0",
                                "1",
                                "2"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Adequate renal function defined as: Normal serum creatinine",
            "criterions": [
                {
                    "exact_snippets": "Adequate renal function defined as: Normal serum creatinine",
                    "criterion": "renal function",
                    "requirements": [
                        {
                            "requirement_type": "serum creatinine level",
                            "expected_value": "normal"
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Normal liver tests (ALT/AST/total bilirubin/triglycerides/cholesterol)",
            "criterions": [
                {
                    "exact_snippets": "Normal liver tests (ALT/AST/total bilirubin/triglycerides/cholesterol)",
                    "criterion": "liver tests",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "normal"
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Recovered from all surgical procedures for at least 7 days (minor procedures) or 28 days (major procedures)",
            "criterions": [
                {
                    "exact_snippets": "Recovered from all surgical procedures for at least 7 days (minor procedures)",
                    "criterion": "recovery from minor surgical procedures",
                    "requirements": [
                        {
                            "requirement_type": "time since procedure",
                            "expected_value": {
                                "operator": ">=",
                                "value": 7,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Recovered from all surgical procedures for at least ... 28 days (major procedures)",
                    "criterion": "recovery from major surgical procedures",
                    "requirements": [
                        {
                            "requirement_type": "time since procedure",
                            "expected_value": {
                                "operator": ">=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "16. Adequate cardiac function defined as: Shortening fraction of ≥ 27% by echocardiogram, or ejection fraction of ≥ 50% by radionuclide angiogram",
            "criterions": [
                {
                    "exact_snippets": "Adequate cardiac function defined as: Shortening fraction of ≥ 27% by echocardiogram",
                    "criterion": "cardiac function",
                    "requirements": [
                        {
                            "requirement_type": "shortening fraction",
                            "expected_value": {
                                "operator": ">=",
                                "value": 27,
                                "unit": "%"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate cardiac function defined as: ... ejection fraction of ≥ 50% by radionuclide angiogram",
                    "criterion": "cardiac function",
                    "requirements": [
                        {
                            "requirement_type": "ejection fraction",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "17. Platelet count 100,000K/uL (transfusion independent), hemoglobin 8.0 g/dL",
            "criterions": [
                {
                    "exact_snippets": "Platelet count 100,000K/uL",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100000,
                                "unit": "K/uL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "transfusion independent",
                    "criterion": "transfusion independence",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "hemoglobin 8.0 g/dL",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 8.0,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "18. Adequate bone marrow function: Peripheral absolute neutrophil count (ANC) 1,000K/uL",
            "criterions": [
                {
                    "exact_snippets": "Adequate bone marrow function: Peripheral absolute neutrophil count (ANC) 1,000K/uL",
                    "criterion": "peripheral absolute neutrophil count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1000,
                                "unit": "K/uL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "19. Signed Informed Consent document and/or Assent document",
            "criterions": [
                {
                    "exact_snippets": "Signed Informed Consent document",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "signed",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Assent document",
                    "criterion": "assent",
                    "requirements": [
                        {
                            "requirement_type": "signed",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 12 Months",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 12 Months",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "Months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have maximum age of 31 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 31 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 31,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. Female patients who are pregnant",
            "criterions": [
                {
                    "exact_snippets": "Female patients",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": "female"
                        }
                    ]
                },
                {
                    "exact_snippets": "who are pregnant",
                    "criterion": "pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Lactating females are not eligible unless they have agreed to discontinue breastfeeding",
            "criterions": [
                {
                    "exact_snippets": "Lactating females are not eligible",
                    "criterion": "lactating females",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "unless they have agreed to discontinue breastfeeding",
                    "criterion": "discontinuation of breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained",
            "criterions": [
                {
                    "exact_snippets": "Female patients of childbearing potential",
                    "criterion": "female patients of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "negative pregnancy test result has been obtained",
                    "criterion": "pregnancy test result",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of study participation",
            "criterions": [
                {
                    "exact_snippets": "Sexually active patients of reproductive potential",
                    "criterion": "sexual activity and reproductive potential",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "agreed to use an effective contraceptive method",
                    "criterion": "contraceptive use",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Any primary central nervous system tumor",
            "criterions": [
                {
                    "exact_snippets": "primary central nervous system tumor",
                    "criterion": "primary central nervous system tumor",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Any patient who has experienced relapsed or refractory disease or a second malignancy.",
            "criterions": [
                {
                    "exact_snippets": "relapsed or refractory disease",
                    "criterion": "disease status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "relapsed",
                                "refractory"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "second malignancy",
                    "criterion": "malignancy",
                    "requirements": [
                        {
                            "requirement_type": "occurrence",
                            "expected_value": "second"
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Any patient not in remission",
            "criterions": [
                {
                    "exact_snippets": "patient not in remission",
                    "criterion": "remission status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "not in remission"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}