{
    "info": {
        "nct_id": "NCT05803382",
        "official_title": "Phase I Trial of ZEN003694 (ZEN-3694) in Combination With Capecitabine in Patients With Solid Tumors",
        "inclusion_criteria": "* Dose Escalation additional criteria: Patients must have histologically confirmed cancer that is metastatic or unresectable and must have progressed on standard therapies which would have included fluorouracil (5-FU) or capecitabine\n* Dose Escalation additional criteria specifically for colorectal cancer (CRC) patients: Willingness and ability to undergo a pre-treatment biopsy\n* Dose Expansion additional criteria: Patients must have histologically confirmed CRC that is metastatic or unresectable and must have progressed on standard therapies which would have included 5-FU or capecitabine\n* Dose Expansion additional criteria: Willingness and ability to undergo pre- and on- treatment biopsies\n* Patients must have measurable disease\n* Age >= 18 years. Because no dosing or adverse event data are currently available on the use of ZEN003694 (ZEN-3694) in combination with capecitabine in patients < 18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Karnofsky >= 60%)\n* Availability of archival tumor tissue at the time of patient enrollment for molecular profiling studies\n* Prior to study dosing, previous systemic therapy must have been completed for at least five half-lives or 2 weeks, whichever is shorter\n* Absolute neutrophil count >= 1,000/mcL\n* Platelets >= 100,000/mcL\n* Total bilirubin =< 1.5 institutional upper limit of normal (ULN)\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN\n* Glomerular filtration rate (GFR) >= 50 mL/min/1.73 m^2\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Patients should be New York Heart Association Functional Classification of class 2B or better\n* The effects of ZEN003694 (ZEN-3694) and capecitabine on the developing human fetus are unknown. For this reason and because BET inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Women of child-bearing potential and men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of ZEN003694 (ZEN-3694) and capecitabine administration\n* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Previous treatment with BET inhibitors\n* History of inability to tolerate capecitabine at the projected treatment dose on this trial\n* Use of oral Factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban otamixaban, letaxaban, eribaxaban) and Factor IIa inhibitors (i.e., dabigatran). Low molecular weight heparin is allowed\n* Treatment for HIV, hepatitis B or hepatitis C only if this interferes with the current treatment (e.g. through drug-drug interactions)\n* Gastrointestinal pathology or history that adversely impacts the ability to take or absorb oral medication\n* Hepatic tumor burden > 30% or peritoneal carcinomatosis\n* Untreated/uncontrolled central nervous system (CNS) disease\n* Known dihydropyrimidine dehydrogenase (DPD) deficiency\n* Severe intercurrent illness or comorbidity\n* Inability to comply with the protocol and/or not willing or who will not be available for follow-up assessments\n* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia and neuropathy up to and including grade 2\n* Patients who are receiving any other investigational agents\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 (ZEN-3694) or other agents used in study\n* Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Strong inhibitors of CYP3A4 must be discontinued at least 7 days, and inducers 14 days prior to the first dose of ZEN003694 and capecitabine. Substrates of CYP1A2 with narrow therapeutic window must be avoided while taking ZEN003694\n* Pregnant women are excluded from this study because ZEN003694 (ZEN-3694) is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ZEN003694 (ZEN-3694), breastfeeding should be discontinued if the mother is treated with ZEN003694 (ZEN-3694). These potential risks may also apply to other agents used in this study",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Dose Escalation additional criteria: Patients must have histologically confirmed cancer that is metastatic or unresectable and must have progressed on standard therapies which would have included fluorouracil (5-FU) or capecitabine",
            "criterions": [
                {
                    "exact_snippets": "histologically confirmed cancer",
                    "criterion": "cancer diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "metastatic or unresectable",
                    "criterion": "cancer stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "metastatic",
                                "unresectable"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "progressed on standard therapies",
                    "criterion": "treatment progression",
                    "requirements": [
                        {
                            "requirement_type": "progression",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "standard therapies which would have included fluorouracil (5-FU) or capecitabine",
                    "criterion": "prior treatment",
                    "requirements": [
                        {
                            "requirement_type": "inclusion",
                            "expected_value": [
                                "fluorouracil (5-FU)",
                                "capecitabine"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Dose Escalation additional criteria specifically for colorectal cancer (CRC) patients: Willingness and ability to undergo a pre-treatment biopsy",
            "criterions": [
                {
                    "exact_snippets": "Willingness and ability to undergo a pre-treatment biopsy",
                    "criterion": "pre-treatment biopsy",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Dose Expansion additional criteria: Patients must have histologically confirmed CRC that is metastatic or unresectable and must have progressed on standard therapies which would have included 5-FU or capecitabine",
            "criterions": [
                {
                    "exact_snippets": "histologically confirmed CRC",
                    "criterion": "CRC (Colorectal Cancer)",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "histologically confirmed"
                        }
                    ]
                },
                {
                    "exact_snippets": "metastatic or unresectable",
                    "criterion": "CRC (Colorectal Cancer)",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "metastatic",
                                "unresectable"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "progressed on standard therapies",
                    "criterion": "progression on standard therapies",
                    "requirements": [
                        {
                            "requirement_type": "progression",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "standard therapies which would have included 5-FU or capecitabine",
                    "criterion": "standard therapies",
                    "requirements": [
                        {
                            "requirement_type": "inclusion",
                            "expected_value": [
                                "5-FU",
                                "capecitabine"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Dose Expansion additional criteria: Willingness and ability to undergo pre- and on- treatment biopsies",
            "criterions": [
                {
                    "exact_snippets": "Willingness and ability to undergo pre- and on- treatment biopsies",
                    "criterion": "biopsy",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have measurable disease",
            "criterions": [
                {
                    "exact_snippets": "measurable disease",
                    "criterion": "disease",
                    "requirements": [
                        {
                            "requirement_type": "measurability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Age >= 18 years. Because no dosing or adverse event data are currently available on the use of ZEN003694 (ZEN-3694) in combination with capecitabine in patients < 18 years of age, children are excluded from this study",
            "criterions": [
                {
                    "exact_snippets": "Age >= 18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Karnofsky >= 60%)",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status of 0-2",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Karnofsky >= 60%",
                    "criterion": "Karnofsky performance status",
                    "requirements": [
                        {
                            "requirement_type": "comparison",
                            "expected_value": {
                                "operator": ">=",
                                "value": 60,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Availability of archival tumor tissue at the time of patient enrollment for molecular profiling studies",
            "criterions": [
                {
                    "exact_snippets": "Availability of archival tumor tissue",
                    "criterion": "archival tumor tissue",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "at the time of patient enrollment",
                    "criterion": "time of availability",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "at the time of patient enrollment"
                        }
                    ]
                },
                {
                    "exact_snippets": "for molecular profiling studies",
                    "criterion": "purpose of tissue availability",
                    "requirements": [
                        {
                            "requirement_type": "purpose",
                            "expected_value": "molecular profiling studies"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior to study dosing, previous systemic therapy must have been completed for at least five half-lives or 2 weeks, whichever is shorter",
            "criterions": [
                {
                    "exact_snippets": "previous systemic therapy must have been completed for at least five half-lives or 2 weeks, whichever is shorter",
                    "criterion": "previous systemic therapy completion",
                    "requirements": [
                        {
                            "requirement_type": "time since completion",
                            "expected_value": "at least five half-lives or 2 weeks, whichever is shorter"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Absolute neutrophil count >= 1,000/mcL",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count >= 1,000/mcL",
                    "criterion": "absolute neutrophil count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1000,
                                "unit": "mcL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelets >= 100,000/mcL",
            "criterions": [
                {
                    "exact_snippets": "Platelets >= 100,000/mcL",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100000,
                                "unit": "mcL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Total bilirubin =< 1.5 institutional upper limit of normal (ULN)",
            "criterions": [
                {
                    "exact_snippets": "Total bilirubin =< 1.5 institutional upper limit of normal (ULN)",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "institutional upper limit of normal (ULN)"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN",
            "criterions": [
                {
                    "exact_snippets": "Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) ... =< 3 x institutional ULN",
                    "criterion": "aspartate aminotransferase (AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "x institutional ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ... =< 3 x institutional ULN",
                    "criterion": "alanine aminotransferase (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "x institutional ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Glomerular filtration rate (GFR) >= 50 mL/min/1.73 m^2",
            "criterions": [
                {
                    "exact_snippets": "Glomerular filtration rate (GFR) >= 50 mL/min/1.73 m^2",
                    "criterion": "glomerular filtration rate (GFR)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "mL/min/1.73 m^2"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial",
            "criterions": [
                {
                    "exact_snippets": "Human immunodeficiency virus (HIV)-infected patients",
                    "criterion": "HIV infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "on effective anti-retroviral therapy",
                    "criterion": "anti-retroviral therapy",
                    "requirements": [
                        {
                            "requirement_type": "effectiveness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "undetectable viral load within 6 months",
                    "criterion": "viral load",
                    "requirements": [
                        {
                            "requirement_type": "detectability",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 6 months"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated",
            "criterions": [
                {
                    "exact_snippets": "evidence of chronic hepatitis B virus (HBV) infection",
                    "criterion": "chronic hepatitis B virus (HBV) infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "HBV viral load must be undetectable",
                    "criterion": "HBV viral load",
                    "requirements": [
                        {
                            "requirement_type": "detectability",
                            "expected_value": "undetectable"
                        }
                    ]
                },
                {
                    "exact_snippets": "on suppressive therapy, if indicated",
                    "criterion": "suppressive therapy",
                    "requirements": [
                        {
                            "requirement_type": "indication",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load",
            "criterions": [
                {
                    "exact_snippets": "history of hepatitis C virus (HCV) infection",
                    "criterion": "history of hepatitis C virus (HCV) infection",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "treated and cured"
                        }
                    ]
                },
                {
                    "exact_snippets": "HCV infection who are currently on treatment ... undetectable HCV viral load",
                    "criterion": "current HCV infection",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "currently on treatment"
                        },
                        {
                            "requirement_type": "viral load",
                            "expected_value": "undetectable"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression",
            "criterions": [
                {
                    "exact_snippets": "Patients with treated brain metastases",
                    "criterion": "brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "follow-up brain imaging ... shows no evidence of progression",
                    "criterion": "brain metastases progression",
                    "requirements": [
                        {
                            "requirement_type": "progression",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial",
            "criterions": [
                {
                    "exact_snippets": "Patients with a prior or concurrent malignancy",
                    "criterion": "prior or concurrent malignancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen",
                    "criterion": "interference with safety or efficacy assessment",
                    "requirements": [
                        {
                            "requirement_type": "potential to interfere",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients should be New York Heart Association Functional Classification of class 2B or better",
            "criterions": [
                {
                    "exact_snippets": "New York Heart Association Functional Classification of class 2B or better",
                    "criterion": "New York Heart Association Functional Classification",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "class"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* The effects of ZEN003694 (ZEN-3694) and capecitabine on the developing human fetus are unknown. For this reason and because BET inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Women of child-bearing potential and men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of ZEN003694 (ZEN-3694) and capecitabine administration",
            "criterions": [
                {
                    "exact_snippets": "women of child-bearing potential",
                    "criterion": "women of child-bearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "men",
                    "criterion": "men",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence)",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "prior to study entry and for the duration of study participation",
                    "criterion": "contraception use duration",
                    "requirements": [
                        {
                            "requirement_type": "time period",
                            "expected_value": "prior to study entry and for the duration of study participation"
                        }
                    ]
                },
                {
                    "exact_snippets": "must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of ZEN003694 (ZEN-3694) and capecitabine administration",
                    "criterion": "contraception use duration",
                    "requirements": [
                        {
                            "requirement_type": "time period",
                            "expected_value": "prior to the study, for the duration of study participation, and 6 months after completion of ZEN003694 (ZEN-3694) and capecitabine administration"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants",
            "criterions": [
                {
                    "exact_snippets": "Ability to understand",
                    "criterion": "cognitive ability",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "willingness to sign a written informed consent document",
                    "criterion": "willingness to consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "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": "* Previous treatment with BET inhibitors",
            "criterions": [
                {
                    "exact_snippets": "Previous treatment with BET inhibitors",
                    "criterion": "BET inhibitors treatment",
                    "requirements": [
                        {
                            "requirement_type": "previous treatment",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of inability to tolerate capecitabine at the projected treatment dose on this trial",
            "criterions": [
                {
                    "exact_snippets": "History of inability to tolerate capecitabine",
                    "criterion": "capecitabine tolerance",
                    "requirements": [
                        {
                            "requirement_type": "tolerance",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Use of oral Factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban otamixaban, letaxaban, eribaxaban) and Factor IIa inhibitors (i.e., dabigatran). Low molecular weight heparin is allowed",
            "criterions": [
                {
                    "exact_snippets": "Use of oral Factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban otamixaban, letaxaban, eribaxaban)",
                    "criterion": "oral Factor Xa inhibitors",
                    "requirements": [
                        {
                            "requirement_type": "use",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Use of ... Factor IIa inhibitors (i.e., dabigatran)",
                    "criterion": "Factor IIa inhibitors",
                    "requirements": [
                        {
                            "requirement_type": "use",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Low molecular weight heparin is allowed",
                    "criterion": "low molecular weight heparin",
                    "requirements": [
                        {
                            "requirement_type": "use",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Treatment for HIV, hepatitis B or hepatitis C only if this interferes with the current treatment (e.g. through drug-drug interactions)",
            "criterions": [
                {
                    "exact_snippets": "Treatment for HIV ... only if this interferes with the current treatment",
                    "criterion": "HIV treatment",
                    "requirements": [
                        {
                            "requirement_type": "interference with current treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Treatment for ... hepatitis B ... only if this interferes with the current treatment",
                    "criterion": "hepatitis B treatment",
                    "requirements": [
                        {
                            "requirement_type": "interference with current treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Treatment for ... hepatitis C only if this interferes with the current treatment",
                    "criterion": "hepatitis C treatment",
                    "requirements": [
                        {
                            "requirement_type": "interference with current treatment",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Gastrointestinal pathology or history that adversely impacts the ability to take or absorb oral medication",
            "criterions": [
                {
                    "exact_snippets": "Gastrointestinal pathology or history that adversely impacts the ability to take or absorb oral medication",
                    "criterion": "gastrointestinal pathology",
                    "requirements": [
                        {
                            "requirement_type": "impact on medication absorption",
                            "expected_value": "adversely impacts"
                        }
                    ]
                },
                {
                    "exact_snippets": "Gastrointestinal pathology or history that adversely impacts the ability to take or absorb oral medication",
                    "criterion": "gastrointestinal history",
                    "requirements": [
                        {
                            "requirement_type": "impact on medication absorption",
                            "expected_value": "adversely impacts"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hepatic tumor burden > 30% or peritoneal carcinomatosis",
            "criterions": [
                {
                    "exact_snippets": "Hepatic tumor burden > 30%",
                    "criterion": "hepatic tumor burden",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">",
                                "value": 30,
                                "unit": "%"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "peritoneal carcinomatosis",
                    "criterion": "peritoneal carcinomatosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Untreated/uncontrolled central nervous system (CNS) disease",
            "criterions": [
                {
                    "exact_snippets": "Untreated/uncontrolled central nervous system (CNS) disease",
                    "criterion": "central nervous system (CNS) disease",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "untreated"
                        },
                        {
                            "requirement_type": "control status",
                            "expected_value": "uncontrolled"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known dihydropyrimidine dehydrogenase (DPD) deficiency",
            "criterions": [
                {
                    "exact_snippets": "Known dihydropyrimidine dehydrogenase (DPD) deficiency",
                    "criterion": "dihydropyrimidine dehydrogenase (DPD) deficiency",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Severe intercurrent illness or comorbidity",
            "criterions": [
                {
                    "exact_snippets": "Severe intercurrent illness",
                    "criterion": "intercurrent illness",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        }
                    ]
                },
                {
                    "exact_snippets": "Severe ... comorbidity",
                    "criterion": "comorbidity",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Inability to comply with the protocol and/or not willing or who will not be available for follow-up assessments",
            "criterions": [
                {
                    "exact_snippets": "Inability to comply with the protocol",
                    "criterion": "protocol compliance",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "not willing",
                    "criterion": "willingness for follow-up assessments",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "not ... available for follow-up assessments",
                    "criterion": "availability for follow-up assessments",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia and neuropathy up to and including grade 2",
            "criterions": [
                {
                    "exact_snippets": "Patients who have not recovered from adverse events due to prior anti-cancer therapy",
                    "criterion": "recovery from adverse events",
                    "requirements": [
                        {
                            "requirement_type": "recovery",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "residual toxicities > grade 1",
                    "criterion": "residual toxicities",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">",
                                "value": 1,
                                "unit": "grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alopecia",
                    "criterion": "alopecia",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "any"
                        }
                    ]
                },
                {
                    "exact_snippets": "neuropathy up to and including grade 2",
                    "criterion": "neuropathy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who are receiving any other investigational agents",
            "criterions": [
                {
                    "exact_snippets": "Patients who are receiving any other investigational agents",
                    "criterion": "investigational agents",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 (ZEN-3694) or other agents used in study",
            "criterions": [
                {
                    "exact_snippets": "History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 (ZEN-3694)",
                    "criterion": "allergic reactions to compounds similar to ZEN003694",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History of allergic reactions attributed to ... other agents used in study",
                    "criterion": "allergic reactions to other agents used in study",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Strong inhibitors of CYP3A4 must be discontinued at least 7 days, and inducers 14 days prior to the first dose of ZEN003694 and capecitabine. Substrates of CYP1A2 with narrow therapeutic window must be avoided while taking ZEN003694",
            "criterions": [
                {
                    "exact_snippets": "Patients receiving any medications or substances that are strong inhibitors ... of CYP3A4 are ineligible.",
                    "criterion": "CYP3A4 strong inhibitors",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients receiving any medications or substances that are strong ... inducers of CYP3A4 are ineligible.",
                    "criterion": "CYP3A4 strong inducers",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Strong inhibitors of CYP3A4 must be discontinued at least 7 days ... prior to the first dose of ZEN003694 and capecitabine.",
                    "criterion": "CYP3A4 strong inhibitors",
                    "requirements": [
                        {
                            "requirement_type": "discontinuation period",
                            "expected_value": {
                                "operator": ">=",
                                "value": 7,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "inducers 14 days prior to the first dose of ZEN003694 and capecitabine.",
                    "criterion": "CYP3A4 strong inducers",
                    "requirements": [
                        {
                            "requirement_type": "discontinuation period",
                            "expected_value": {
                                "operator": ">=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Substrates of CYP1A2 with narrow therapeutic window must be avoided while taking ZEN003694",
                    "criterion": "CYP1A2 substrates with narrow therapeutic window",
                    "requirements": [
                        {
                            "requirement_type": "avoidance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant women are excluded from this study because ZEN003694 (ZEN-3694) is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ZEN003694 (ZEN-3694), breastfeeding should be discontinued if the mother is treated with ZEN003694 (ZEN-3694). These potential risks may also apply to other agents used in this study",
            "criterions": [
                {
                    "exact_snippets": "Pregnant women are excluded",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "breastfeeding should be discontinued",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}