{
    "info": {
        "nct_id": "NCT02734160",
        "official_title": "A Phase 1b Dose-Escalation and Cohort-Expansion Study of the Safety, Tolerability, and Efficacy of a Novel Transforming Growth Factor-β Receptor I Kinase Inhibitor (Galunisertib) Administered in Combination With the Anti-PD-L1 Antibody Durvalumab (MEDI4736) in Recurrent or Refractory Metastatic Pancreatic Cancer",
        "inclusion_criteria": "* Must have histologic or cytologic confirmation of recurrent metastatic pancreatic adenocarcinoma based on standard diagnostic criteria. Recurrence must be documented by diagnostic biopsy.\n* Have measurable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.\n* Have had disease progression, been refractory or intolerant to no more than 2 prior systemic regimens for locally advanced or metastatic pancreatic cancer. Participants who have received prior neoadjuvant therapy and who now have metastatic disease must have received 1 of the following for their metastatic disease: FOLFIRINOX, nanoparticle albumin-bound paclitaxel/gemcitabine, TS-1 (tegafur gimeracil oteracil potassium), irinotecan liposome injection/5-fluorouracil (5FU)/Leucovorin or single-agent gemcitabine prior to enrolment in this study.\n* Dose Escalation: Able and willing to give valid written consent to undergo a new tumour biopsy (prior to study treatment) or to provide an available archival tumour sample if taken <3 years prior to enrolment if a new tumour biopsy is not feasible with an acceptable clinical risk.\n* Cohort Expansion: Able and willing to give valid written consent to undergo a new tumour biopsy (prior to study treatment). Able and willing to undergo a second tumour biopsy on treatment. Where possible, tumour lesions used for new biopsies should not be the same lesions used as RECIST target lesions, unless there are no other lesions suitable for biopsy. Archival samples may be required if there is inadequate tissue in the biopsy specimen.\n* Have adequate organ function.\n* Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale.\n* Use approved contraceptive methods.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Have moderate or severe cardiovascular disease:\n\n  * Have the presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension.\n  * Have documented major electrocardiogram (ECG) abnormalities (not responding to medical treatments; for example, atrial fibrillation, bundle branch blocks, or as approved by the sponsors).\n  * Have major abnormalities documented by ECHO with Doppler (for example, moderate or severe heart valve function defect including moderate or severe valve stenosis or regurgitation, left ventricular ejection fraction <50%, evaluation based on the institutional lower limit of normal, septal aneurysm or other heart aneurysm, any aneurysm of the major vessels or any condition that results in increased risk of aneurysm (eg, Marfan syndrome, patent foramen ovale [PFO]).\n  * Have predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, family history of aneurysms, Marfan syndrome, PFO, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by computerized tomography [CT] scan with contrast or magnetic resonance imaging [MRI]).\n* Have evidence of interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity or active, noninfectious pneumonitis.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Must have histologic or cytologic confirmation of recurrent metastatic pancreatic adenocarcinoma based on standard diagnostic criteria. Recurrence must be documented by diagnostic biopsy.",
            "criterions": [
                {
                    "exact_snippets": "Must have histologic or cytologic confirmation of recurrent metastatic pancreatic adenocarcinoma",
                    "criterion": "recurrent metastatic pancreatic adenocarcinoma",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": [
                                "histologic",
                                "cytologic"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Recurrence must be documented by diagnostic biopsy",
                    "criterion": "recurrence",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": "diagnostic biopsy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Have measurable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.",
            "criterions": [
                {
                    "exact_snippets": "Have measurable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.",
                    "criterion": "measurable disease",
                    "requirements": [
                        {
                            "requirement_type": "definition",
                            "expected_value": "Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Have had disease progression, been refractory or intolerant to no more than 2 prior systemic regimens for locally advanced or metastatic pancreatic cancer. Participants who have received prior neoadjuvant therapy and who now have metastatic disease must have received 1 of the following for their metastatic disease: FOLFIRINOX, nanoparticle albumin-bound paclitaxel/gemcitabine, TS-1 (tegafur gimeracil oteracil potassium), irinotecan liposome injection/5-fluorouracil (5FU)/Leucovorin or single-agent gemcitabine prior to enrolment in this study.",
            "criterions": [
                {
                    "exact_snippets": "Have had disease progression",
                    "criterion": "disease progression",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "been refractory or intolerant to no more than 2 prior systemic regimens",
                    "criterion": "refractory or intolerant to prior systemic regimens",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "regimens"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "locally advanced or metastatic pancreatic cancer",
                    "criterion": "pancreatic cancer stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "locally advanced",
                                "metastatic"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Participants who have received prior neoadjuvant therapy and who now have metastatic disease must have received 1 of the following for their metastatic disease: FOLFIRINOX, nanoparticle albumin-bound paclitaxel/gemcitabine, TS-1 (tegafur gimeracil oteracil potassium), irinotecan liposome injection/5-fluorouracil (5FU)/Leucovorin or single-agent gemcitabine",
                    "criterion": "prior treatment for metastatic disease",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": [
                                "FOLFIRINOX",
                                "nanoparticle albumin-bound paclitaxel/gemcitabine",
                                "TS-1 (tegafur gimeracil oteracil potassium)",
                                "irinotecan liposome injection/5-fluorouracil (5FU)/Leucovorin",
                                "single-agent gemcitabine"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Dose Escalation: Able and willing to give valid written consent to undergo a new tumour biopsy (prior to study treatment) or to provide an available archival tumour sample if taken <3 years prior to enrolment if a new tumour biopsy is not feasible with an acceptable clinical risk.",
            "criterions": [
                {
                    "exact_snippets": "Able and willing to give valid written consent",
                    "criterion": "written consent",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "undergo a new tumour biopsy (prior to study treatment)",
                    "criterion": "new tumour biopsy",
                    "requirements": [
                        {
                            "requirement_type": "feasibility",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "provide an available archival tumour sample if taken <3 years prior to enrolment",
                    "criterion": "archival tumour sample",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time since taken",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Cohort Expansion: Able and willing to give valid written consent to undergo a new tumour biopsy (prior to study treatment). Able and willing to undergo a second tumour biopsy on treatment. Where possible, tumour lesions used for new biopsies should not be the same lesions used as RECIST target lesions, unless there are no other lesions suitable for biopsy. Archival samples may be required if there is inadequate tissue in the biopsy specimen.",
            "criterions": [
                {
                    "exact_snippets": "Able and willing to give valid written consent",
                    "criterion": "written consent",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "undergo a new tumour biopsy (prior to study treatment)",
                    "criterion": "new tumour biopsy (prior to study treatment)",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "undergo a second tumour biopsy on treatment",
                    "criterion": "second tumour biopsy on treatment",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "tumour lesions used for new biopsies should not be the same lesions used as RECIST target lesions",
                    "criterion": "tumour lesions for new biopsies",
                    "requirements": [
                        {
                            "requirement_type": "distinct from RECIST target lesions",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Archival samples may be required if there is inadequate tissue in the biopsy specimen",
                    "criterion": "archival samples",
                    "requirements": [
                        {
                            "requirement_type": "requirement condition",
                            "expected_value": "if there is inadequate tissue in the biopsy specimen"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Have adequate organ function.",
            "criterions": [
                {
                    "exact_snippets": "adequate organ function",
                    "criterion": "organ function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale.",
            "criterions": [
                {
                    "exact_snippets": "performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale",
                    "criterion": "performance status",
                    "requirements": [
                        {
                            "requirement_type": "scale",
                            "expected_value": "Eastern Cooperative Oncology Group (ECOG)"
                        },
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "=",
                                        "value": 1,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Use approved contraceptive methods.",
            "criterions": [
                {
                    "exact_snippets": "Use approved contraceptive methods.",
                    "criterion": "contraceptive methods",
                    "requirements": [
                        {
                            "requirement_type": "use",
                            "expected_value": "approved"
                        }
                    ]
                }
            ]
        },
        {
            "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": "* Have moderate or severe cardiovascular disease:",
            "criterions": [
                {
                    "exact_snippets": "moderate or severe cardiovascular disease",
                    "criterion": "cardiovascular disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "moderate",
                                "severe"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Have the presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension.",
            "criterions": [
                {
                    "exact_snippets": "presence of cardiac disease",
                    "criterion": "cardiac disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "myocardial infarction within 6 months prior to study entry",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "unstable angina pectoris",
                    "criterion": "unstable angina pectoris",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "New York Heart Association Class III/IV congestive heart failure",
                    "criterion": "New York Heart Association Class III/IV congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled hypertension",
                    "criterion": "uncontrolled hypertension",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Have documented major electrocardiogram (ECG) abnormalities (not responding to medical treatments; for example, atrial fibrillation, bundle branch blocks, or as approved by the sponsors).",
            "criterions": [
                {
                    "exact_snippets": "documented major electrocardiogram (ECG) abnormalities",
                    "criterion": "major ECG abnormalities",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "not responding to medical treatments",
                    "criterion": "response to medical treatments",
                    "requirements": [
                        {
                            "requirement_type": "response",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "atrial fibrillation",
                    "criterion": "atrial fibrillation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "bundle branch blocks",
                    "criterion": "bundle branch blocks",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Have major abnormalities documented by ECHO with Doppler (for example, moderate or severe heart valve function defect including moderate or severe valve stenosis or regurgitation, left ventricular ejection fraction <50%, evaluation based on the institutional lower limit of normal, septal aneurysm or other heart aneurysm, any aneurysm of the major vessels or any condition that results in increased risk of aneurysm (eg, Marfan syndrome, patent foramen ovale [PFO]).",
            "criterions": [
                {
                    "exact_snippets": "major abnormalities documented by ECHO with Doppler",
                    "criterion": "major abnormalities",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": "ECHO with Doppler"
                        }
                    ]
                },
                {
                    "exact_snippets": "moderate or severe heart valve function defect",
                    "criterion": "heart valve function defect",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "moderate",
                                "severe"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "moderate or severe valve stenosis or regurgitation",
                    "criterion": "valve stenosis or regurgitation",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "moderate",
                                "severe"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "left ventricular ejection fraction <50%",
                    "criterion": "left ventricular ejection fraction",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "septal aneurysm or other heart aneurysm",
                    "criterion": "heart aneurysm",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "any aneurysm of the major vessels",
                    "criterion": "aneurysm of the major vessels",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "any condition that results in increased risk of aneurysm (eg, Marfan syndrome, patent foramen ovale [PFO])",
                    "criterion": "condition that results in increased risk of aneurysm",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Have predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, family history of aneurysms, Marfan syndrome, PFO, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by computerized tomography [CT] scan with contrast or magnetic resonance imaging [MRI]).",
            "criterions": [
                {
                    "exact_snippets": "predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress",
                    "criterion": "predisposing conditions for aneurysms of the ascending aorta or aortic stress",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "family history of aneurysms",
                    "criterion": "family history of aneurysms",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Marfan syndrome",
                    "criterion": "Marfan syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "PFO",
                    "criterion": "PFO",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "bicuspid aortic valve",
                    "criterion": "bicuspid aortic valve",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "evidence of damage to the large vessels of the heart documented by computerized tomography [CT] scan with contrast or magnetic resonance imaging [MRI]",
                    "criterion": "evidence of damage to the large vessels of the heart",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": [
                                "CT scan with contrast",
                                "MRI"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Have evidence of interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity or active, noninfectious pneumonitis.",
            "criterions": [
                {
                    "exact_snippets": "evidence of interstitial lung disease",
                    "criterion": "interstitial lung disease",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "interstitial lung disease that is symptomatic",
                    "criterion": "interstitial lung disease",
                    "requirements": [
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "interstitial lung disease ... may interfere with the detection or management of suspected drug-related pulmonary toxicity",
                    "criterion": "interstitial lung disease",
                    "requirements": [
                        {
                            "requirement_type": "interference with detection or management of drug-related pulmonary toxicity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "active, noninfectious pneumonitis",
                    "criterion": "pneumonitis",
                    "requirements": [
                        {
                            "requirement_type": "active",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "infectious",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}