{
    "info": {
        "nct_id": "NCT02108782",
        "official_title": "Phase II Study of Dovitinib (TKI-258) in Progressive, Well-Differentiated Pancreatic Neuroendocrine Tumors With and Without Prior VEGF-Inhibitor Therapy",
        "inclusion_criteria": "* Histologic diagnosis of a well- to moderately differentiated PNET (low-intermediate grade); NOTE: pathology report should state one of the following: low-grade, intermediate grade, moderately- or well-differentiated NET, pancreatic NET (or neuroendocrine carcinoma of the pancreas); patients who have tumors with a Ki67 of 20 % - 30 % are eligible if the pathologist determines the tumor has the appearance of a well- to moderately differentiated neuroendocrine tumor\n* Documented radiological evidence for disease progression (measurable or nonmeasurable) =< 12 months prior to enrollment; NOTE: if the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation; at least one measurable lesion as per Response Evaluation Criteria In Solid Tumors (RECIST)\n* Disease that is currently not amenable to surgery, radiation, or combined modality therapy with curative intent\n* COHORT 2 ONLY: Prior treatment with a VEGF inhibitor (e.g. sunitinib, bevacizumab, sorafenib or other dedicated VEGF inhibitor)\n* Recovered from adverse events (to grade 1 or less toxicity according to Common Terminology Criteria for Adverse Events [CTCAE] 4.0) due to agents administered previously; NOTE: chemotherapy-induced alopecia and grade 2 neuropathy are acceptable\n* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1\n* Absolute neutrophil count (ANC) >= 1.5 x 10^9/L\n* Platelets >= 100 x 10^9/L\n* Hemoglobin (Hgb) > 9 g/dL\n* Serum total bilirubin =< 1.5 x upper limit of normal (ULN)\n* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3.0 x ULN\n* Serum creatinine =< 1.5 x ULN\n* Provide informed written consent\n* Negative pregnancy test done =< 14 days prior to registration, for women of childbearing potential only\n* Willing to return to an Academic and Community Cancer Research United (ACCRU) enrolling institution for follow-up (i.e., active monitoring, which includes active treatment and observation)\n* Willing to provide mandatory blood samples for correlative research purposes\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Clinical evidence for brain metastases (including carcinomatous meningitis) at baseline (may require imaging assessment, e.g. computed tomography [CT] or magnetic resonance imaging [MRI], for certain patient population), with the exception of those subjects who have previously-treated central nervous system (CNS) metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have had no requirement for steroids or enzyme- inducing anticonvulsants within 6 months prior to study entry\n* Participated in a prior anticancer investigational study =< 30 days prior to enrollment, or =< 5 half-lives of the anticancer investigational product, whichever is longer (treatment with somatostatin analogue [SSTa] while on dovitinib is allowed provided patient's tumor has progressed on therapy prior to initiating dovitinib treatment)\n* COHORT 1 ONLY: Prior treatment with a VEGF inhibitor (e.g. sunitinib, bevacizumab, sorafenib or other dedicated VEGF inhibitor)\n* Liver-directed therapy (hepatic artery chemoembolization [HACE], hepatic artery embolization [HAE], selective internal radiation therapy [SIRT]) or peptide receptor radionuclide therapy (PRRT) =< 56 days of first dose of study drug\n* Another primary malignancy =< 3 years prior to starting study treatment, with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer, or in-situ carcinoma of the uterine cervix\n* Received the last administration of an anticancer targeted small molecule therapy (e.g. sunitinib, sorafenib, pazopanib, axitinib, everolimus, temsirolimus, ridaforolimus) =< 14 days prior to study registration or have not recovered from the side effects of such therapy\n* Received the last administration of an anticancer monoclonal antibody, immunotherapy, hormonal therapy, or chemotherapy (except nitrosoureas and mitomycin-C) =< 28 days prior to study registration or who have not recovered from the side effects of such therapy\n* Received the last administration of nitrosourea or mitomycin-C =< 42 days prior to study registration, or who have not recovered from the side effects of such therapy\n* Radiotherapy (external beam or CyberKnife) =< 28 days prior to starting study drug, or =< 14 days prior to study registration in the case of localized radiotherapy (e.g. for analgesic purpose or for lytic lesions at risk of fracture), or who have not recovered from radiotherapy toxicities\n* Undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury =< 28 days prior to study registration, or had minor procedures, percutaneous biopsies or placement of vascular access device =< 7 days prior to study registration, or have not recovered from side effects of such procedure or injury\n* History of pulmonary embolism (PE), or untreated deep venous thrombosis (DVT) =< 180 days\n* Impaired cardiac function or clinically significant cardiac diseases, including any of the following:\n\n  * History or presence of serious uncontrolled ventricular arrhythmias\n  * Clinically significant resting bradycardia\n  * Ongoing cardiac dysrhythmias, atrial fibrillation, or prolongation of corrected QTc interval to > 480 msec\n\n    • * Left ventricular ejection fraction (LVEF) assessed by 2-dimensional (2-D) echocardiogram (ECHO) < 50% or lower limit of normal (whichever is the higher), or 2-D multiple gated acquisition scan (MUGA) < 45% or lower limit of normal (whichever is the higher)\n  * Any of the following =< 180 days prior to starting study drug: myocardial infarction (MI), severe/unstable angina, coronary artery bypass graft (CABG), congestive heart failure (CHF), cerebrovascular accident (CVA), transient ischemic attack (TIA)\n  * Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mm Hg and/or diastolic (D)BP >= 100 mm Hg, with or without anti-hypertensive medication(s); initiation or adjustment of antihypertensive medication(s) is allowed prior to study entry\n* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or gastric or small bowel resection)\n* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to registration\n* No clinically significant gastrointestinal abnormalities that may increase the risk of gastrointestinal bleeding within 28 days prior to registration including, but not limited to:\n\n  * Active peptic ulcer\n  * Known endoluminal metastatic lesion(s) with history of bleeding\n  * Active inflammatory bowel disease (e.g. ulcerative colitis, Crohn's Disease), or other gastrointestinal conditions with increased risk of perforation\n* No evidence of active bleeding, bleeding diathesis, or hemoptysis (>= ½ teaspoon of red blood) within 8 weeks of registration\n* Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy (HIV testing not required); NOTE: patients known to be HIV positive, but without clinical evidence of an immunocompromised state (cluster of differentiation [CD]4 > 200, viral load undetectable, on antiretroviral therapy), are eligible for this trial\n* Currently receiving antiplatelet therapy of prasugrel or clopidogrel, or full dose anticoagulation treatment with therapeutic doses of warfarin; Note: treatment with low doses of warfarin (e.g., =< 2 mg/day ) for line patency allowed; also, low molecular weight heparins, fondaparinux, antiaggregation agents (e.g., eptifibatide, epoprostenol, dipyridamole) or locally accepted low doses of acetylsalicylic acid (up to 100 mg daily) may be administered concomitantly with dovitinib with caution\n* Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol\n* Any of the following:\n\n  * Pregnant women\n  * Nursing women\n  * Men or women of childbearing potential who are unwilling to employ adequate contraception\n* Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test\n* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception (defined below); highly effective contraception must be used by both sexes (female patients and their male partners) during study treatment and for 30 days after the last dose of study medication; highly effective contraception methods include:\n\n  * Total abstinence (when this is in line with the preferred and usual lifestyle of the subject); periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\n  * Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment\n  * Combination of the following:\n\n    * Placement of an intrauterine device (IUD) or intrauterine system (IUS)\n    * Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository\n* Oral, implantable, or injectable hormone contraceptives are not considered effective for this study\n* Women of child-bearing potential (sexually mature women) who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test =< 14 days prior to starting study drug\n* Fertile males not willing to use contraception; fertile males must use condom with spermicide; highly effective contraception, as defined above, must be used by both sexes (male patients and their female partners) during study treatment and for 90 days after the last dose of study medication and should not father a child in this period; a condom is required to be used also by vasectomized men\n* Unwilling or unable to comply with the protocol\n* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens\n* Currently receiving any other investigational agent which would be considered as a treatment for the primary neoplasm",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Histologic diagnosis of a well- to moderately differentiated PNET (low-intermediate grade); NOTE: pathology report should state one of the following: low-grade, intermediate grade, moderately- or well-differentiated NET, pancreatic NET (or neuroendocrine carcinoma of the pancreas); patients who have tumors with a Ki67 of 20 % - 30 % are eligible if the pathologist determines the tumor has the appearance of a well- to moderately differentiated neuroendocrine tumor",
            "criterions": [
                {
                    "exact_snippets": "Histologic diagnosis of a well- to moderately differentiated PNET (low-intermediate grade)",
                    "criterion": "histologic diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": "well- to moderately differentiated PNET (low-intermediate grade)"
                        }
                    ]
                },
                {
                    "exact_snippets": "pathology report should state one of the following: low-grade, intermediate grade, moderately- or well-differentiated NET, pancreatic NET (or neuroendocrine carcinoma of the pancreas)",
                    "criterion": "pathology report",
                    "requirements": [
                        {
                            "requirement_type": "statement",
                            "expected_value": [
                                "low-grade",
                                "intermediate grade",
                                "moderately- or well-differentiated NET",
                                "pancreatic NET",
                                "neuroendocrine carcinoma of the pancreas"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "patients who have tumors with a Ki67 of 20 % - 30 % are eligible",
                    "criterion": "Ki67",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 20,
                                        "unit": "%"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 30,
                                        "unit": "%"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "if the pathologist determines the tumor has the appearance of a well- to moderately differentiated neuroendocrine tumor",
                    "criterion": "tumor appearance",
                    "requirements": [
                        {
                            "requirement_type": "determination",
                            "expected_value": "well- to moderately differentiated neuroendocrine tumor"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Documented radiological evidence for disease progression (measurable or nonmeasurable) =< 12 months prior to enrollment; NOTE: if the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation; at least one measurable lesion as per Response Evaluation Criteria In Solid Tumors (RECIST)",
            "criterions": [
                {
                    "exact_snippets": "Documented radiological evidence for disease progression (measurable or nonmeasurable) =< 12 months prior to enrollment",
                    "criterion": "disease progression",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 12,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "if the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation",
                    "criterion": "progression since radiation",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "at least one measurable lesion as per Response Evaluation Criteria In Solid Tumors (RECIST)",
                    "criterion": "measurable lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "lesion"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Disease that is currently not amenable to surgery, radiation, or combined modality therapy with curative intent",
            "criterions": [
                {
                    "exact_snippets": "Disease that is currently not amenable to surgery",
                    "criterion": "disease amenability to surgery",
                    "requirements": [
                        {
                            "requirement_type": "amenability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Disease that is currently not amenable to ... radiation",
                    "criterion": "disease amenability to radiation",
                    "requirements": [
                        {
                            "requirement_type": "amenability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Disease that is currently not amenable to ... combined modality therapy with curative intent",
                    "criterion": "disease amenability to combined modality therapy with curative intent",
                    "requirements": [
                        {
                            "requirement_type": "amenability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* COHORT 2 ONLY: Prior treatment with a VEGF inhibitor (e.g. sunitinib, bevacizumab, sorafenib or other dedicated VEGF inhibitor)",
            "criterions": [
                {
                    "exact_snippets": "Prior treatment with a VEGF inhibitor (e.g. sunitinib, bevacizumab, sorafenib or other dedicated VEGF inhibitor)",
                    "criterion": "prior treatment with a VEGF inhibitor",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Recovered from adverse events (to grade 1 or less toxicity according to Common Terminology Criteria for Adverse Events [CTCAE] 4.0) due to agents administered previously; NOTE: chemotherapy-induced alopecia and grade 2 neuropathy are acceptable",
            "criterions": [
                {
                    "exact_snippets": "Recovered from adverse events (to grade 1 or less toxicity according to Common Terminology Criteria for Adverse Events [CTCAE] 4.0)",
                    "criterion": "recovery from adverse events",
                    "requirements": [
                        {
                            "requirement_type": "toxicity level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "chemotherapy-induced alopecia",
                    "criterion": "chemotherapy-induced alopecia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "grade 2 neuropathy",
                    "criterion": "neuropathy",
                    "requirements": [
                        {
                            "requirement_type": "toxicity level",
                            "expected_value": {
                                "operator": "=",
                                "value": 2,
                                "unit": "grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Absolute neutrophil count (ANC) >= 1.5 x 10^9/L",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count (ANC) >= 1.5 x 10^9/L",
                    "criterion": "absolute neutrophil count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "x 10^9/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelets >= 100 x 10^9/L",
            "criterions": [
                {
                    "exact_snippets": "Platelets >= 100 x 10^9/L",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100,
                                "unit": "x 10^9/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hemoglobin (Hgb) > 9 g/dL",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin (Hgb) > 9 g/dL",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 9,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Serum total bilirubin =< 1.5 x upper limit of normal (ULN)",
            "criterions": [
                {
                    "exact_snippets": "Serum total bilirubin =< 1.5 x upper limit of normal (ULN)",
                    "criterion": "serum total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3.0 x ULN",
            "criterions": [
                {
                    "exact_snippets": "Alanine aminotransferase (ALT) ... =< 3.0 x ULN",
                    "criterion": "Alanine aminotransferase (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3.0,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "aspartate aminotransferase (AST) =< 3.0 x ULN",
                    "criterion": "aspartate aminotransferase (AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3.0,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Serum creatinine =< 1.5 x ULN",
            "criterions": [
                {
                    "exact_snippets": "Serum creatinine =< 1.5 x ULN",
                    "criterion": "serum creatinine",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Provide informed written consent",
            "criterions": [
                {
                    "exact_snippets": "Provide informed written consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Negative pregnancy test done =< 14 days prior to registration, for women of childbearing potential only",
            "criterions": [
                {
                    "exact_snippets": "Negative pregnancy test ... for women of childbearing potential only",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        },
                        {
                            "requirement_type": "applicability",
                            "expected_value": "women of childbearing potential"
                        }
                    ]
                },
                {
                    "exact_snippets": "Negative pregnancy test done =< 14 days prior to registration",
                    "criterion": "pregnancy test timing",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 14,
                                "unit": "days prior to registration"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Willing to return to an Academic and Community Cancer Research United (ACCRU) enrolling institution for follow-up (i.e., active monitoring, which includes active treatment and observation)",
            "criterions": [
                {
                    "exact_snippets": "Willing to return to an Academic and Community Cancer Research United (ACCRU) enrolling institution for follow-up",
                    "criterion": "willingness to return for follow-up",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "active monitoring, which includes active treatment and observation",
                    "criterion": "active monitoring",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Willing to provide mandatory blood samples for correlative research purposes",
            "criterions": [
                {
                    "exact_snippets": "Willing to provide mandatory blood samples",
                    "criterion": "blood samples",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "mandatory",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 18 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "* Clinical evidence for brain metastases (including carcinomatous meningitis) at baseline (may require imaging assessment, e.g. computed tomography [CT] or magnetic resonance imaging [MRI], for certain patient population), with the exception of those subjects who have previously-treated central nervous system (CNS) metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have had no requirement for steroids or enzyme- inducing anticonvulsants within 6 months prior to study entry",
            "criterions": [
                {
                    "exact_snippets": "Clinical evidence for brain metastases (including carcinomatous meningitis) at baseline",
                    "criterion": "brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "imaging assessment, e.g. computed tomography [CT] or magnetic resonance imaging [MRI]",
                    "criterion": "imaging assessment",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "computed tomography",
                                "magnetic resonance imaging"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "previously-treated central nervous system (CNS) metastases (surgery ± radiotherapy, radiosurgery, or gamma knife)",
                    "criterion": "previously-treated CNS metastases",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": [
                                "surgery",
                                "radiotherapy",
                                "radiosurgery",
                                "gamma knife"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "asymptomatic",
                    "criterion": "symptoms",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "no requirement for steroids or enzyme- inducing anticonvulsants within 6 months prior to study entry",
                    "criterion": "steroid or enzyme-inducing anticonvulsant requirement",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participated in a prior anticancer investigational study =< 30 days prior to enrollment, or =< 5 half-lives of the anticancer investigational product, whichever is longer (treatment with somatostatin analogue [SSTa] while on dovitinib is allowed provided patient's tumor has progressed on therapy prior to initiating dovitinib treatment)",
            "criterions": [
                {
                    "exact_snippets": "Participated in a prior anticancer investigational study =< 30 days prior to enrollment",
                    "criterion": "prior anticancer investigational study participation",
                    "requirements": [
                        {
                            "requirement_type": "time since participation",
                            "expected_value": {
                                "operator": "<=",
                                "value": 30,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "=< 5 half-lives of the anticancer investigational product",
                    "criterion": "half-lives of anticancer investigational product",
                    "requirements": [
                        {
                            "requirement_type": "time since participation",
                            "expected_value": {
                                "operator": "<=",
                                "value": 5,
                                "unit": "half-lives"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "treatment with somatostatin analogue [SSTa] while on dovitinib is allowed provided patient's tumor has progressed on therapy prior to initiating dovitinib treatment",
                    "criterion": "treatment with somatostatin analogue [SSTa] while on dovitinib",
                    "requirements": [
                        {
                            "requirement_type": "tumor progression on therapy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* COHORT 1 ONLY: Prior treatment with a VEGF inhibitor (e.g. sunitinib, bevacizumab, sorafenib or other dedicated VEGF inhibitor)",
            "criterions": [
                {
                    "exact_snippets": "Prior treatment with a VEGF inhibitor (e.g. sunitinib, bevacizumab, sorafenib or other dedicated VEGF inhibitor)",
                    "criterion": "prior treatment with a VEGF inhibitor",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Liver-directed therapy (hepatic artery chemoembolization [HACE], hepatic artery embolization [HAE], selective internal radiation therapy [SIRT]) or peptide receptor radionuclide therapy (PRRT) =< 56 days of first dose of study drug",
            "criterions": [
                {
                    "exact_snippets": "Liver-directed therapy (hepatic artery chemoembolization [HACE], hepatic artery embolization [HAE], selective internal radiation therapy [SIRT]) or peptide receptor radionuclide therapy (PRRT) =< 56 days of first dose of study drug",
                    "criterion": "liver-directed therapy or peptide receptor radionuclide therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 56,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Another primary malignancy =< 3 years prior to starting study treatment, with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer, or in-situ carcinoma of the uterine cervix",
            "criterions": [
                {
                    "exact_snippets": "Another primary malignancy =< 3 years prior to starting study treatment",
                    "criterion": "primary malignancy",
                    "requirements": [
                        {
                            "requirement_type": "time since diagnosis",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer",
                    "criterion": "skin cancer",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "adequately treated"
                        }
                    ]
                },
                {
                    "exact_snippets": "in-situ carcinoma of the uterine cervix",
                    "criterion": "in-situ carcinoma of the uterine cervix",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Received the last administration of an anticancer targeted small molecule therapy (e.g. sunitinib, sorafenib, pazopanib, axitinib, everolimus, temsirolimus, ridaforolimus) =< 14 days prior to study registration or have not recovered from the side effects of such therapy",
            "criterions": [
                {
                    "exact_snippets": "Received the last administration of an anticancer targeted small molecule therapy (e.g. sunitinib, sorafenib, pazopanib, axitinib, everolimus, temsirolimus, ridaforolimus) =< 14 days prior to study registration",
                    "criterion": "time since last anticancer targeted small molecule therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since administration",
                            "expected_value": {
                                "operator": "<=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "have not recovered from the side effects of such therapy",
                    "criterion": "recovery from side effects of anticancer targeted small molecule therapy",
                    "requirements": [
                        {
                            "requirement_type": "recovery",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Received the last administration of an anticancer monoclonal antibody, immunotherapy, hormonal therapy, or chemotherapy (except nitrosoureas and mitomycin-C) =< 28 days prior to study registration or who have not recovered from the side effects of such therapy",
            "criterions": [
                {
                    "exact_snippets": "Received the last administration of an anticancer monoclonal antibody, immunotherapy, hormonal therapy, or chemotherapy (except nitrosoureas and mitomycin-C) =< 28 days prior to study registration",
                    "criterion": "time since last administration of specific therapies",
                    "requirements": [
                        {
                            "requirement_type": "time since administration",
                            "expected_value": {
                                "operator": "<=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "who have not recovered from the side effects of such therapy",
                    "criterion": "recovery from side effects of therapy",
                    "requirements": [
                        {
                            "requirement_type": "recovery status",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Received the last administration of nitrosourea or mitomycin-C =< 42 days prior to study registration, or who have not recovered from the side effects of such therapy",
            "criterions": [
                {
                    "exact_snippets": "Received the last administration of nitrosourea or mitomycin-C =< 42 days prior to study registration",
                    "criterion": "time since last administration of nitrosourea or mitomycin-C",
                    "requirements": [
                        {
                            "requirement_type": "time since administration",
                            "expected_value": {
                                "operator": "<=",
                                "value": 42,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "who have not recovered from the side effects of such therapy",
                    "criterion": "recovery from side effects of nitrosourea or mitomycin-C",
                    "requirements": [
                        {
                            "requirement_type": "recovery",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Radiotherapy (external beam or CyberKnife) =< 28 days prior to starting study drug, or =< 14 days prior to study registration in the case of localized radiotherapy (e.g. for analgesic purpose or for lytic lesions at risk of fracture), or who have not recovered from radiotherapy toxicities",
            "criterions": [
                {
                    "exact_snippets": "Radiotherapy (external beam or CyberKnife) =< 28 days prior to starting study drug",
                    "criterion": "radiotherapy timing before study drug",
                    "requirements": [
                        {
                            "requirement_type": "time since radiotherapy",
                            "expected_value": {
                                "operator": "<=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "localized radiotherapy ... =< 14 days prior to study registration",
                    "criterion": "localized radiotherapy timing before study registration",
                    "requirements": [
                        {
                            "requirement_type": "time since radiotherapy",
                            "expected_value": {
                                "operator": "<=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "who have not recovered from radiotherapy toxicities",
                    "criterion": "recovery from radiotherapy toxicities",
                    "requirements": [
                        {
                            "requirement_type": "recovery",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury =< 28 days prior to study registration, or had minor procedures, percutaneous biopsies or placement of vascular access device =< 7 days prior to study registration, or have not recovered from side effects of such procedure or injury",
            "criterions": [
                {
                    "exact_snippets": "Undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury =< 28 days prior to study registration",
                    "criterion": "major surgery, open biopsy, or significant traumatic injury",
                    "requirements": [
                        {
                            "requirement_type": "time since procedure",
                            "expected_value": {
                                "operator": "<=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "had minor procedures, percutaneous biopsies or placement of vascular access device =< 7 days prior to study registration",
                    "criterion": "minor procedures, percutaneous biopsies, or placement of vascular access device",
                    "requirements": [
                        {
                            "requirement_type": "time since procedure",
                            "expected_value": {
                                "operator": "<=",
                                "value": 7,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "have not recovered from side effects of such procedure or injury",
                    "criterion": "recovery from side effects of procedure or injury",
                    "requirements": [
                        {
                            "requirement_type": "recovery status",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of pulmonary embolism (PE), or untreated deep venous thrombosis (DVT) =< 180 days",
            "criterions": [
                {
                    "exact_snippets": "History of pulmonary embolism (PE)",
                    "criterion": "pulmonary embolism (PE)",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "untreated deep venous thrombosis (DVT) =< 180 days",
                    "criterion": "deep venous thrombosis (DVT)",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "untreated"
                        },
                        {
                            "requirement_type": "time since diagnosis",
                            "expected_value": {
                                "operator": "<=",
                                "value": 180,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Impaired cardiac function or clinically significant cardiac diseases, including any of the following:",
            "criterions": [
                {
                    "exact_snippets": "Impaired cardiac function",
                    "criterion": "cardiac function",
                    "requirements": [
                        {
                            "requirement_type": "impairment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "clinically significant cardiac diseases",
                    "criterion": "cardiac diseases",
                    "requirements": [
                        {
                            "requirement_type": "clinical significance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History or presence of serious uncontrolled ventricular arrhythmias",
            "criterions": [
                {
                    "exact_snippets": "History or presence of serious uncontrolled ventricular arrhythmias",
                    "criterion": "ventricular arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "severity",
                            "expected_value": "serious"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Clinically significant resting bradycardia",
            "criterions": [
                {
                    "exact_snippets": "Clinically significant resting bradycardia",
                    "criterion": "resting bradycardia",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "clinically significant"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Ongoing cardiac dysrhythmias, atrial fibrillation, or prolongation of corrected QTc interval to > 480 msec",
            "criterions": [
                {
                    "exact_snippets": "Ongoing cardiac dysrhythmias",
                    "criterion": "cardiac dysrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "atrial fibrillation",
                    "criterion": "atrial fibrillation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "prolongation of corrected QTc interval to > 480 msec",
                    "criterion": "corrected QTc interval",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 480,
                                "unit": "msec"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "• * Left ventricular ejection fraction (LVEF) assessed by 2-dimensional (2-D) echocardiogram (ECHO) < 50% or lower limit of normal (whichever is the higher), or 2-D multiple gated acquisition scan (MUGA) < 45% or lower limit of normal (whichever is the higher)",
            "criterions": [
                {
                    "exact_snippets": "Left ventricular ejection fraction (LVEF) assessed by 2-dimensional (2-D) echocardiogram (ECHO) < 50% or lower limit of normal (whichever is the higher)",
                    "criterion": "left ventricular ejection fraction (LVEF) by 2-D echocardiogram (ECHO)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 50,
                                        "unit": "%"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 0,
                                        "unit": "lower limit of normal"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "2-D multiple gated acquisition scan (MUGA) < 45% or lower limit of normal (whichever is the higher)",
                    "criterion": "left ventricular ejection fraction (LVEF) by 2-D multiple gated acquisition scan (MUGA)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 45,
                                        "unit": "%"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 0,
                                        "unit": "lower limit of normal"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any of the following =< 180 days prior to starting study drug: myocardial infarction (MI), severe/unstable angina, coronary artery bypass graft (CABG), congestive heart failure (CHF), cerebrovascular accident (CVA), transient ischemic attack (TIA)",
            "criterions": [
                {
                    "exact_snippets": "myocardial infarction (MI) ... =< 180 days prior to starting study drug",
                    "criterion": "myocardial infarction (MI)",
                    "requirements": [
                        {
                            "requirement_type": "occurrence",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 180,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "severe/unstable angina ... =< 180 days prior to starting study drug",
                    "criterion": "severe/unstable angina",
                    "requirements": [
                        {
                            "requirement_type": "occurrence",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 180,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "coronary artery bypass graft (CABG) ... =< 180 days prior to starting study drug",
                    "criterion": "coronary artery bypass graft (CABG)",
                    "requirements": [
                        {
                            "requirement_type": "occurrence",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 180,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "congestive heart failure (CHF) ... =< 180 days prior to starting study drug",
                    "criterion": "congestive heart failure (CHF)",
                    "requirements": [
                        {
                            "requirement_type": "occurrence",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 180,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "cerebrovascular accident (CVA) ... =< 180 days prior to starting study drug",
                    "criterion": "cerebrovascular accident (CVA)",
                    "requirements": [
                        {
                            "requirement_type": "occurrence",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 180,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "transient ischemic attack (TIA) ... =< 180 days prior to starting study drug",
                    "criterion": "transient ischemic attack (TIA)",
                    "requirements": [
                        {
                            "requirement_type": "occurrence",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 180,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mm Hg and/or diastolic (D)BP >= 100 mm Hg, with or without anti-hypertensive medication(s); initiation or adjustment of antihypertensive medication(s) is allowed prior to study entry",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mm Hg",
                    "criterion": "systolic blood pressure",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 160,
                                "unit": "mm Hg"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled hypertension defined by ... diastolic (D)BP >= 100 mm Hg",
                    "criterion": "diastolic blood pressure",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100,
                                "unit": "mm Hg"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or gastric or small bowel resection)",
            "criterions": [
                {
                    "exact_snippets": "Impairment of gastrointestinal (GI) function or GI disease",
                    "criterion": "gastrointestinal (GI) function or GI disease",
                    "requirements": [
                        {
                            "requirement_type": "impairment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ulcerative diseases",
                    "criterion": "ulcerative diseases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled nausea",
                    "criterion": "nausea",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "vomiting",
                    "criterion": "vomiting",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "diarrhea",
                    "criterion": "diarrhea",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "malabsorption syndrome",
                    "criterion": "malabsorption syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "gastric or small bowel resection",
                    "criterion": "gastric or small bowel resection",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to registration",
            "criterions": [
                {
                    "exact_snippets": "History of abdominal fistula",
                    "criterion": "abdominal fistula",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "History of ... gastrointestinal perforation",
                    "criterion": "gastrointestinal perforation",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "History of ... intra-abdominal abscess",
                    "criterion": "intra-abdominal abscess",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No clinically significant gastrointestinal abnormalities that may increase the risk of gastrointestinal bleeding within 28 days prior to registration including, but not limited to:",
            "criterions": [
                {
                    "exact_snippets": "clinically significant gastrointestinal abnormalities",
                    "criterion": "gastrointestinal abnormalities",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "not clinically significant"
                        }
                    ]
                },
                {
                    "exact_snippets": "increase the risk of gastrointestinal bleeding",
                    "criterion": "risk of gastrointestinal bleeding",
                    "requirements": [
                        {
                            "requirement_type": "risk",
                            "expected_value": "not increased"
                        }
                    ]
                },
                {
                    "exact_snippets": "within 28 days prior to registration",
                    "criterion": "time frame for gastrointestinal bleeding risk",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "28 days prior to registration"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active peptic ulcer",
            "criterions": [
                {
                    "exact_snippets": "Active peptic ulcer",
                    "criterion": "peptic ulcer",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "active"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known endoluminal metastatic lesion(s) with history of bleeding",
            "criterions": [
                {
                    "exact_snippets": "Known endoluminal metastatic lesion(s)",
                    "criterion": "endoluminal metastatic lesion",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of bleeding",
                    "criterion": "history of bleeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active inflammatory bowel disease (e.g. ulcerative colitis, Crohn's Disease), or other gastrointestinal conditions with increased risk of perforation",
            "criterions": [
                {
                    "exact_snippets": "Active inflammatory bowel disease (e.g. ulcerative colitis, Crohn's Disease)",
                    "criterion": "inflammatory bowel disease",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                },
                {
                    "exact_snippets": "other gastrointestinal conditions with increased risk of perforation",
                    "criterion": "gastrointestinal conditions",
                    "requirements": [
                        {
                            "requirement_type": "risk of perforation",
                            "expected_value": "increased"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No evidence of active bleeding, bleeding diathesis, or hemoptysis (>= ½ teaspoon of red blood) within 8 weeks of registration",
            "criterions": [
                {
                    "exact_snippets": "No evidence of active bleeding",
                    "criterion": "active bleeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "No evidence of ... bleeding diathesis",
                    "criterion": "bleeding diathesis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "No evidence of ... hemoptysis (>= ½ teaspoon of red blood) within 8 weeks of registration",
                    "criterion": "hemoptysis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 0.5,
                                "unit": "teaspoon"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy (HIV testing not required); NOTE: patients known to be HIV positive, but without clinical evidence of an immunocompromised state (cluster of differentiation [CD]4 > 200, viral load undetectable, on antiretroviral therapy), are eligible for this trial",
            "criterions": [
                {
                    "exact_snippets": "Immunocompromised patients",
                    "criterion": "immunocompromised state",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "patients known to be human immunodeficiency virus (HIV) positive",
                    "criterion": "HIV status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "currently receiving antiretroviral therapy",
                    "criterion": "antiretroviral therapy",
                    "requirements": [
                        {
                            "requirement_type": "current treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "patients known to be HIV positive, but without clinical evidence of an immunocompromised state (cluster of differentiation [CD]4 > 200, viral load undetectable, on antiretroviral therapy)",
                    "criterion": "clinical evidence of an immunocompromised state",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "cluster of differentiation [CD]4 > 200",
                    "criterion": "CD4 count",
                    "requirements": [
                        {
                            "requirement_type": "count",
                            "expected_value": {
                                "operator": ">",
                                "value": 200,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "viral load undetectable",
                    "criterion": "viral load",
                    "requirements": [
                        {
                            "requirement_type": "detectability",
                            "expected_value": "undetectable"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Currently receiving antiplatelet therapy of prasugrel or clopidogrel, or full dose anticoagulation treatment with therapeutic doses of warfarin; Note: treatment with low doses of warfarin (e.g., =< 2 mg/day ) for line patency allowed; also, low molecular weight heparins, fondaparinux, antiaggregation agents (e.g., eptifibatide, epoprostenol, dipyridamole) or locally accepted low doses of acetylsalicylic acid (up to 100 mg daily) may be administered concomitantly with dovitinib with caution",
            "criterions": [
                {
                    "exact_snippets": "Currently receiving antiplatelet therapy of prasugrel or clopidogrel",
                    "criterion": "antiplatelet therapy",
                    "requirements": [
                        {
                            "requirement_type": "medication",
                            "expected_value": [
                                "prasugrel",
                                "clopidogrel"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "full dose anticoagulation treatment with therapeutic doses of warfarin",
                    "criterion": "anticoagulation treatment",
                    "requirements": [
                        {
                            "requirement_type": "medication",
                            "expected_value": "warfarin"
                        },
                        {
                            "requirement_type": "dose",
                            "expected_value": "therapeutic"
                        }
                    ]
                },
                {
                    "exact_snippets": "treatment with low doses of warfarin (e.g., =< 2 mg/day ) for line patency allowed",
                    "criterion": "warfarin dose",
                    "requirements": [
                        {
                            "requirement_type": "dose",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "mg/day"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "low molecular weight heparins, fondaparinux, antiaggregation agents (e.g., eptifibatide, epoprostenol, dipyridamole)",
                    "criterion": "concomitant medications",
                    "requirements": [
                        {
                            "requirement_type": "medication",
                            "expected_value": [
                                "low molecular weight heparins",
                                "fondaparinux",
                                "eptifibatide",
                                "epoprostenol",
                                "dipyridamole"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "locally accepted low doses of acetylsalicylic acid (up to 100 mg daily)",
                    "criterion": "acetylsalicylic acid dose",
                    "requirements": [
                        {
                            "requirement_type": "dose",
                            "expected_value": {
                                "operator": "<=",
                                "value": 100,
                                "unit": "mg daily"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol",
            "criterions": [
                {
                    "exact_snippets": "Other concurrent severe and/or uncontrolled concomitant medical conditions",
                    "criterion": "concomitant medical conditions",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        },
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        }
                    ]
                },
                {
                    "exact_snippets": "active or uncontrolled infection",
                    "criterion": "infection",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        },
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled diabetes",
                    "criterion": "diabetes",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant women",
            "criterions": [
                {
                    "exact_snippets": "Pregnant women",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Nursing women",
            "criterions": [
                {
                    "exact_snippets": "Nursing women",
                    "criterion": "nursing status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "nursing"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Men or women of childbearing potential who are unwilling to employ adequate contraception",
            "criterions": [
                {
                    "exact_snippets": "Men or women of childbearing potential",
                    "criterion": "childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "unwilling to employ adequate contraception",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test",
            "criterions": [
                {
                    "exact_snippets": "Pregnant ... confirmed by a positive human chorionic gonadotropin (hCG) laboratory test",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "positive human chorionic gonadotropin (hCG) laboratory test"
                        }
                    ]
                },
                {
                    "exact_snippets": "nursing (lactating) women",
                    "criterion": "nursing",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception (defined below); highly effective contraception must be used by both sexes (female patients and their male partners) during study treatment and for 30 days after the last dose of study medication; highly effective contraception methods include:",
            "criterions": [
                {
                    "exact_snippets": "Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant",
                    "criterion": "women of child-bearing potential",
                    "requirements": [
                        {
                            "requirement_type": "definition",
                            "expected_value": "all women physiologically capable of becoming pregnant"
                        }
                    ]
                },
                {
                    "exact_snippets": "unless they are using highly effective methods of contraception",
                    "criterion": "use of highly effective contraception",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "highly effective contraception must be used by both sexes (female patients and their male partners) during study treatment and for 30 days after the last dose of study medication",
                    "criterion": "duration of contraception use",
                    "requirements": [
                        {
                            "requirement_type": "time period",
                            "expected_value": "during study treatment and for 30 days after the last dose of study medication"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject); periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception",
            "criterions": [
                {
                    "exact_snippets": "Total abstinence (when this is in line with the preferred and usual lifestyle of the subject)",
                    "criterion": "total abstinence",
                    "requirements": [
                        {
                            "requirement_type": "lifestyle alignment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods)",
                    "criterion": "periodic abstinence",
                    "requirements": [
                        {
                            "requirement_type": "acceptability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "withdrawal are not acceptable methods of contraception",
                    "criterion": "withdrawal method",
                    "requirements": [
                        {
                            "requirement_type": "acceptability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment",
            "criterions": [
                {
                    "exact_snippets": "Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy)",
                    "criterion": "female sterilization",
                    "requirements": [
                        {
                            "requirement_type": "procedure",
                            "expected_value": [
                                "surgical bilateral oophorectomy",
                                "hysterectomy"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "tubal ligation at least six weeks before taking study treatment",
                    "criterion": "tubal ligation",
                    "requirements": [
                        {
                            "requirement_type": "time since procedure",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment",
                    "criterion": "reproductive status confirmation",
                    "requirements": [
                        {
                            "requirement_type": "procedure",
                            "expected_value": "oophorectomy alone"
                        },
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": "follow up hormone level assessment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Placement of an intrauterine device (IUD) or intrauterine system (IUS)",
            "criterions": [
                {
                    "exact_snippets": "Placement of an intrauterine device (IUD) or intrauterine system (IUS)",
                    "criterion": "intrauterine device (IUD) or intrauterine system (IUS)",
                    "requirements": [
                        {
                            "requirement_type": "placement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository",
            "criterions": [
                {
                    "exact_snippets": "Barrier methods of contraception: condom",
                    "criterion": "contraception method",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": "condom"
                        }
                    ]
                },
                {
                    "exact_snippets": "Barrier methods of contraception: ... occlusive cap (diaphragm or cervical/vault caps)",
                    "criterion": "contraception method",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "diaphragm",
                                "cervical cap",
                                "vault cap"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Barrier methods of contraception: ... with spermicidal foam/gel/film/cream/vaginal suppository",
                    "criterion": "contraception method",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "spermicidal foam",
                                "spermicidal gel",
                                "spermicidal film",
                                "spermicidal cream",
                                "spermicidal vaginal suppository"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Oral, implantable, or injectable hormone contraceptives are not considered effective for this study",
            "criterions": [
                {
                    "exact_snippets": "Oral, implantable, or injectable hormone contraceptives are not considered effective",
                    "criterion": "hormone contraceptives",
                    "requirements": [
                        {
                            "requirement_type": "effectiveness",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women of child-bearing potential (sexually mature women) who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test =< 14 days prior to starting study drug",
            "criterions": [
                {
                    "exact_snippets": "Women of child-bearing potential (sexually mature women)",
                    "criterion": "sex",
                    "requirements": [
                        {
                            "requirement_type": "expected sex",
                            "expected_value": "female"
                        }
                    ]
                },
                {
                    "exact_snippets": "Women of child-bearing potential (sexually mature women)",
                    "criterion": "child-bearing potential",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "who have not undergone a hysterectomy",
                    "criterion": "hysterectomy",
                    "requirements": [
                        {
                            "requirement_type": "procedure undergone",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "who have not been naturally postmenopausal for at least 12 consecutive months",
                    "criterion": "menopausal status",
                    "requirements": [
                        {
                            "requirement_type": "postmenopausal duration",
                            "expected_value": {
                                "operator": "<",
                                "value": 12,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "must have a negative serum pregnancy test =< 14 days prior to starting study drug",
                    "criterion": "serum pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        },
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Fertile males not willing to use contraception; fertile males must use condom with spermicide; highly effective contraception, as defined above, must be used by both sexes (male patients and their female partners) during study treatment and for 90 days after the last dose of study medication and should not father a child in this period; a condom is required to be used also by vasectomized men",
            "criterions": [
                {
                    "exact_snippets": "Fertile males not willing to use contraception",
                    "criterion": "fertile males",
                    "requirements": [
                        {
                            "requirement_type": "willingness to use contraception",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "fertile males must use condom with spermicide",
                    "criterion": "fertile males",
                    "requirements": [
                        {
                            "requirement_type": "contraception method",
                            "expected_value": "condom with spermicide"
                        }
                    ]
                },
                {
                    "exact_snippets": "highly effective contraception, as defined above, must be used by both sexes (male patients and their female partners) during study treatment and for 90 days after the last dose of study medication",
                    "criterion": "contraception",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "during study treatment and for 90 days after the last dose of study medication"
                        }
                    ]
                },
                {
                    "exact_snippets": "should not father a child in this period",
                    "criterion": "fertile males",
                    "requirements": [
                        {
                            "requirement_type": "fathering a child",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "a condom is required to be used also by vasectomized men",
                    "criterion": "vasectomized men",
                    "requirements": [
                        {
                            "requirement_type": "contraception method",
                            "expected_value": "condom"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Unwilling or unable to comply with the protocol",
            "criterions": [
                {
                    "exact_snippets": "Unwilling or unable to comply with the protocol",
                    "criterion": "compliance with the protocol",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens",
            "criterions": [
                {
                    "exact_snippets": "Co-morbid systemic illnesses",
                    "criterion": "co-morbid systemic illnesses",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "other severe concurrent disease",
                    "criterion": "severe concurrent disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Currently receiving any other investigational agent which would be considered as a treatment for the primary neoplasm",
            "criterions": [
                {
                    "exact_snippets": "Currently receiving any other investigational agent which would be considered as a treatment for the primary neoplasm",
                    "criterion": "receiving investigational agent",
                    "requirements": [
                        {
                            "requirement_type": "purpose",
                            "expected_value": "treatment for the primary neoplasm"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [
        {
            "line": "* Any of the following:",
            "criterions": []
        },
        {
            "line": "* Combination of the following:",
            "criterions": []
        }
    ],
    "failed_miscellaneous": []
}