{
    "info": {
        "nct_id": "NCT01877382",
        "official_title": "A Phase 1 Multiple Ascending Dose Study of Milademetan in Subjects With Advanced Solid Tumors or Lymphomas",
        "inclusion_criteria": "Dose Escalation Cohorts (Part 1)\n\n* Has a histologically or cytologically documented advanced solid tumor or lymphoma that has relapsed from or is refractory to standard treatment, or for which no standard treatment is available.\n\n  * Participants with melanoma who are ineligible to receive or have declined ipilimumab treatment or who are refractory or intolerant to ipilimumab may enroll.\n  * Participants with certain tumor types such as those with high prevalence of MDM2 amplification or overexpression (eg, well-differentiated [WD]/dedifferentiated [DD] liposarcoma) may be preferentially enrolled in Part 1.\n\nDose Expansion Cohort (Part 2)\n\n* Has a histologically or cytologically documented advanced melanoma or diffuse large B cell lymphoma (DLBCL), with measurable disease that is refractory to standard treatment or for which no standard treatment is available.\n\n  * Participants with melanoma who are ineligible to receive or have declined ipilimumab treatment or who are refractory or intolerant to ipilimumab may enroll.\n  * Participants with DLBCL who have failed, been deemed ineligible for, or refused autologous stem cell transplantation may enroll.\n* Man or woman ≥ 18 years old.\n* Has an Eastern Cooperative Oncology Group (ECOG) performance status 0-1.\n* Has adequate bone marrow function, defined as:\n\n  * Platelet count ≥ 100 x 10^9/L\n  * Hemoglobin ≥ 9.0 g/dL\n  * Absolute neutrophil count ≥ 1.5 x 10^9/L.\n* Has adequate renal function, defined as creatinine clearance ≥ 60 mL/min, as calculated using the modified Cockcroft Gault equation, ([{140 - age in years} × {actual weight in kg}] divided by [{72 × serum creatinine in mg/dL} multiply by 0.85 if female]), OR creatinine ≤ 1.5 x ULN.\n* Has adequate hepatic function, defined as:\n\n  * AST/ALT levels ≤ 3 x ULN (if liver metastases are present, ≤ 5 x ULN)\n  * Bilirubin ≤ 1.5 x ULN.\n* Has adequate blood clotting function, defined as International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN.\n* Participant should be able to provide written informed consent, comply with protocol visits and procedures, be able to take oral medication, and not have any active infection or comorbidity that would interfere with therapy.\n* Participant (male and female) of childbearing/reproductive potential must agree to use double-barrier contraceptive measures or avoid intercourse during the study and for 90 days after the last dose of study drug.\n* Participant must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign and date an IRB [Institutional Review Board]-approved Informed consent Form [ICF] (including Health Insurance Portability and Accountability Act authorization, if applicable) before performance of any study specific procedures or tests.\n* Is willing to provide and there is confirmed availability of pre-existing diagnostic or resected tumor samples, such as paraffin-embedded sections. Providing fresh tumor biopsy is optional for participants in Dose Escalation cohorts.\n* Is willing to undergo tumor genotyping for TP53 mutation, insertion, or deletion at screening. Confirmation of TP53 nonmutant status is encouraged, but not required prior to milademetan dosing.\n* Is willing to provide additional archived samples for comprehensive genomic and/or proteomic analyses if the participant has a partial response/complete response to milademetan treatment.\n* Is willing to undergo pre-treatment tumor biopsies (Part 2 only)\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Has a tumor that contains an inactivating mutation, insertion, or deletion in the TP53 gene determined previously or at screening.\n* Has a history of primary central nervous system malignancy.\n* Has gastrointestinal conditions that could affect the absorption of milademetan in the opinion of the Investigator.\n* Has an uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals, known human immunodeficiency virus infection, or active hepatitis B or C infection.\n* Has received an allogeneic bone marrow or allogeneic stem cell transplant.\n* Has a concomitant medical condition that would increase the risk of toxicity, in the opinion of the Investigator or Sponsor.\n* Has clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with steroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 4 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment (2 weeks for stereotactic radiotherapy).\n* Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE v4, grade ≤ 1 or baseline. Participants with chronic grade 2 toxicities may be eligible per the discretion of the Investigator and Sponsor (eg, grade 2 chemotherapy-induced neuropathy).\n* Had an autologous transplant within 3 months of starting study drug treatment.\n* Is receiving concomitant treatment with a strong inducer of CYP3A.\n* Had systemic treatment with anticancer therapy, antibody-based therapy, retinoid therapy, or hormonal therapy within 3 weeks before study drug treatment; or treatment with nitrosoureas or mitomycin C within 6 weeks before study drug treatment; or treatment with small-molecule targeted agents within 2 weeks before study drug treatment. Previous and concurrent use of hormone replacement therapy, the use of gonadotropin releasing hormone modulators for prostate cancer, and the use of somatostatin analogs for neuroendocrine tumors are permitted if such therapy has not been changed within 8 weeks before study drug treatment.\n* Had therapeutic radiation therapy or major surgery within 4 weeks before study drug treatment or palliative radiation therapy within 2 weeks before study drug treatment.\n* Participated in a therapeutic clinical study within 3 weeks before study drug treatment, or current participation in other therapeutic investigational procedures.\n* Prolongation of corrected QT interval by Fridericia's method (QTcF) at rest, where the mean QTcF interval is > 450 milliseconds (ms) for males and > 470 ms for females based on triplicate ECG.\n* Pregnant or breastfeeding.\n* Substance abuse or medical, psychological, or social conditions that, in the opinion of the Investigator, may interfere with the participant's participation in the clinical study or evaluation of the clinical study results.\n* Prior treatment with an MDM2 inhibitor.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "Dose Escalation Cohorts (Part 1)",
            "criterions": [
                {
                    "exact_snippets": "Dose Escalation Cohorts",
                    "criterion": "dose escalation",
                    "requirements": [
                        {
                            "requirement_type": "phase",
                            "expected_value": "Part 1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has a histologically or cytologically documented advanced solid tumor or lymphoma that has relapsed from or is refractory to standard treatment, or for which no standard treatment is available.",
            "criterions": [
                {
                    "exact_snippets": "histologically or cytologically documented advanced solid tumor or lymphoma",
                    "criterion": "advanced solid tumor or lymphoma",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "relapsed from or is refractory to standard treatment",
                    "criterion": "response to standard treatment",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "relapsed",
                                "refractory"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "no standard treatment is available",
                    "criterion": "availability of standard treatment",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants with melanoma who are ineligible to receive or have declined ipilimumab treatment or who are refractory or intolerant to ipilimumab may enroll.",
            "criterions": [
                {
                    "exact_snippets": "Participants with melanoma",
                    "criterion": "melanoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ineligible to receive ... ipilimumab treatment",
                    "criterion": "ipilimumab treatment eligibility",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "have declined ipilimumab treatment",
                    "criterion": "ipilimumab treatment acceptance",
                    "requirements": [
                        {
                            "requirement_type": "acceptance",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "refractory ... to ipilimumab",
                    "criterion": "ipilimumab treatment response",
                    "requirements": [
                        {
                            "requirement_type": "response",
                            "expected_value": "refractory"
                        }
                    ]
                },
                {
                    "exact_snippets": "intolerant to ipilimumab",
                    "criterion": "ipilimumab treatment tolerance",
                    "requirements": [
                        {
                            "requirement_type": "tolerance",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants with certain tumor types such as those with high prevalence of MDM2 amplification or overexpression (eg, well-differentiated [WD]/dedifferentiated [DD] liposarcoma) may be preferentially enrolled in Part 1.",
            "criterions": [
                {
                    "exact_snippets": "tumor types such as those with high prevalence of MDM2 amplification or overexpression",
                    "criterion": "tumor type",
                    "requirements": [
                        {
                            "requirement_type": "prevalence of MDM2 amplification or overexpression",
                            "expected_value": "high"
                        }
                    ]
                },
                {
                    "exact_snippets": "well-differentiated [WD]/dedifferentiated [DD] liposarcoma",
                    "criterion": "tumor type",
                    "requirements": [
                        {
                            "requirement_type": "specific types",
                            "expected_value": [
                                "well-differentiated liposarcoma",
                                "dedifferentiated liposarcoma"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "Dose Expansion Cohort (Part 2)",
            "criterions": [
                {
                    "exact_snippets": "Dose Expansion Cohort (Part 2)",
                    "criterion": "cohort",
                    "requirements": [
                        {
                            "requirement_type": "name",
                            "expected_value": "Dose Expansion Cohort (Part 2)"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has a histologically or cytologically documented advanced melanoma or diffuse large B cell lymphoma (DLBCL), with measurable disease that is refractory to standard treatment or for which no standard treatment is available.",
            "criterions": [
                {
                    "exact_snippets": "histologically or cytologically documented advanced melanoma",
                    "criterion": "advanced melanoma",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "histologically or cytologically documented ... diffuse large B cell lymphoma (DLBCL)",
                    "criterion": "diffuse large B cell lymphoma (DLBCL)",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "measurable disease",
                    "criterion": "disease measurability",
                    "requirements": [
                        {
                            "requirement_type": "measurability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "refractory to standard treatment",
                    "criterion": "refractory to standard treatment",
                    "requirements": [
                        {
                            "requirement_type": "refractoriness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "no standard treatment is available",
                    "criterion": "availability of standard treatment",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants with melanoma who are ineligible to receive or have declined ipilimumab treatment or who are refractory or intolerant to ipilimumab may enroll.",
            "criterions": [
                {
                    "exact_snippets": "Participants with melanoma",
                    "criterion": "melanoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ineligible to receive ... ipilimumab treatment",
                    "criterion": "ipilimumab treatment eligibility",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "have declined ipilimumab treatment",
                    "criterion": "ipilimumab treatment acceptance",
                    "requirements": [
                        {
                            "requirement_type": "acceptance",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "refractory ... to ipilimumab",
                    "criterion": "ipilimumab treatment refractoriness",
                    "requirements": [
                        {
                            "requirement_type": "refractoriness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "intolerant to ipilimumab",
                    "criterion": "ipilimumab treatment tolerance",
                    "requirements": [
                        {
                            "requirement_type": "tolerance",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants with DLBCL who have failed, been deemed ineligible for, or refused autologous stem cell transplantation may enroll.",
            "criterions": [
                {
                    "exact_snippets": "Participants with DLBCL",
                    "criterion": "DLBCL",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "failed, been deemed ineligible for, or refused autologous stem cell transplantation",
                    "criterion": "autologous stem cell transplantation",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "failed",
                                "ineligible",
                                "refused"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Man or woman ≥ 18 years old.",
            "criterions": [
                {
                    "exact_snippets": "Man or woman",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "man",
                                "woman"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "≥ 18 years old",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has an Eastern Cooperative Oncology Group (ECOG) performance status 0-1.",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status 0-1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 1,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has adequate bone marrow function, defined as:",
            "criterions": [
                {
                    "exact_snippets": "adequate bone marrow function",
                    "criterion": "bone marrow function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelet count ≥ 100 x 10^9/L",
            "criterions": [
                {
                    "exact_snippets": "Platelet count ≥ 100 x 10^9/L",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100,
                                "unit": "x 10^9/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hemoglobin ≥ 9.0 g/dL",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin ≥ 9.0 g/dL",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9.0,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Absolute neutrophil count ≥ 1.5 x 10^9/L.",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count ≥ 1.5 x 10^9/L",
                    "criterion": "absolute neutrophil count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "x 10^9/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has adequate renal function, defined as creatinine clearance ≥ 60 mL/min, as calculated using the modified Cockcroft Gault equation, ([{140 - age in years} × {actual weight in kg}] divided by [{72 × serum creatinine in mg/dL} multiply by 0.85 if female]), OR creatinine ≤ 1.5 x ULN.",
            "criterions": [
                {
                    "exact_snippets": "adequate renal function, defined as creatinine clearance ≥ 60 mL/min, as calculated using the modified Cockcroft Gault equation",
                    "criterion": "renal function",
                    "requirements": [
                        {
                            "requirement_type": "creatinine clearance",
                            "expected_value": {
                                "operator": ">=",
                                "value": 60,
                                "unit": "mL/min"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "creatinine ≤ 1.5 x ULN",
                    "criterion": "creatinine level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has adequate hepatic function, defined as:",
            "criterions": [
                {
                    "exact_snippets": "adequate hepatic function",
                    "criterion": "hepatic function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* AST/ALT levels ≤ 3 x ULN (if liver metastases are present, ≤ 5 x ULN)",
            "criterions": [
                {
                    "exact_snippets": "AST/ALT levels ≤ 3 x ULN",
                    "criterion": "AST/ALT levels",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "if liver metastases are present, ≤ 5 x ULN",
                    "criterion": "AST/ALT levels with liver metastases",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Bilirubin ≤ 1.5 x ULN.",
            "criterions": [
                {
                    "exact_snippets": "Bilirubin ≤ 1.5 x ULN.",
                    "criterion": "bilirubin level",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has adequate blood clotting function, defined as International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN.",
            "criterions": [
                {
                    "exact_snippets": "adequate blood clotting function, defined as International normalized ratio (INR) ... ≤ 1.5 x ULN",
                    "criterion": "International normalized ratio (INR)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "adequate blood clotting function, defined as ... activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN",
                    "criterion": "activated partial thromboplastin time (aPTT)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participant should be able to provide written informed consent, comply with protocol visits and procedures, be able to take oral medication, and not have any active infection or comorbidity that would interfere with therapy.",
            "criterions": [
                {
                    "exact_snippets": "Participant should be able to provide written informed consent",
                    "criterion": "ability to provide written informed consent",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "comply with protocol visits and procedures",
                    "criterion": "compliance with protocol visits and procedures",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "be able to take oral medication",
                    "criterion": "ability to take oral medication",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "not have any active infection",
                    "criterion": "active infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "not have any ... comorbidity that would interfere with therapy",
                    "criterion": "comorbidity that would interfere with therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participant (male and female) of childbearing/reproductive potential must agree to use double-barrier contraceptive measures or avoid intercourse during the study and for 90 days after the last dose of study drug.",
            "criterions": [
                {
                    "exact_snippets": "Participant (male and female) of childbearing/reproductive potential",
                    "criterion": "childbearing/reproductive potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must agree to use double-barrier contraceptive measures or avoid intercourse during the study and for 90 days after the last dose of study drug",
                    "criterion": "contraceptive measures or intercourse avoidance",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participant must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign and date an IRB [Institutional Review Board]-approved Informed consent Form [ICF] (including Health Insurance Portability and Accountability Act authorization, if applicable) before performance of any study specific procedures or tests.",
            "criterions": [
                {
                    "exact_snippets": "Participant must be fully informed about their illness",
                    "criterion": "participant information about illness",
                    "requirements": [
                        {
                            "requirement_type": "informed",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "investigational nature of the study protocol (including foreseeable risks and possible side effects)",
                    "criterion": "participant information about study protocol",
                    "requirements": [
                        {
                            "requirement_type": "informed",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must sign and date an IRB [Institutional Review Board]-approved Informed consent Form [ICF]",
                    "criterion": "informed consent form",
                    "requirements": [
                        {
                            "requirement_type": "signed and dated",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Health Insurance Portability and Accountability Act authorization, if applicable",
                    "criterion": "HIPAA authorization",
                    "requirements": [
                        {
                            "requirement_type": "authorization",
                            "expected_value": "if applicable"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Is willing to provide and there is confirmed availability of pre-existing diagnostic or resected tumor samples, such as paraffin-embedded sections. Providing fresh tumor biopsy is optional for participants in Dose Escalation cohorts.",
            "criterions": [
                {
                    "exact_snippets": "willing to provide ... pre-existing diagnostic or resected tumor samples",
                    "criterion": "willingness to provide tumor samples",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "confirmed availability of pre-existing diagnostic or resected tumor samples",
                    "criterion": "availability of pre-existing tumor samples",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Providing fresh tumor biopsy is optional for participants in Dose Escalation cohorts",
                    "criterion": "fresh tumor biopsy",
                    "requirements": [
                        {
                            "requirement_type": "requirement",
                            "expected_value": "optional for participants in Dose Escalation cohorts"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Is willing to undergo tumor genotyping for TP53 mutation, insertion, or deletion at screening. Confirmation of TP53 nonmutant status is encouraged, but not required prior to milademetan dosing.",
            "criterions": [
                {
                    "exact_snippets": "willing to undergo tumor genotyping for TP53 mutation, insertion, or deletion",
                    "criterion": "willingness to undergo tumor genotyping",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "tumor genotyping for TP53 mutation, insertion, or deletion",
                    "criterion": "TP53 mutation, insertion, or deletion",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Confirmation of TP53 nonmutant status is encouraged, but not required",
                    "criterion": "TP53 nonmutant status",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "encouraged, but not required"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Is willing to provide additional archived samples for comprehensive genomic and/or proteomic analyses if the participant has a partial response/complete response to milademetan treatment.",
            "criterions": [
                {
                    "exact_snippets": "willing to provide additional archived samples",
                    "criterion": "willingness to provide samples",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "comprehensive genomic and/or proteomic analyses",
                    "criterion": "analyses type",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "genomic",
                                "proteomic"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "partial response/complete response to milademetan treatment",
                    "criterion": "response to milademetan treatment",
                    "requirements": [
                        {
                            "requirement_type": "response",
                            "expected_value": [
                                "partial response",
                                "complete response"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Is willing to undergo pre-treatment tumor biopsies (Part 2 only)",
            "criterions": [
                {
                    "exact_snippets": "willing to undergo pre-treatment tumor biopsies",
                    "criterion": "willingness to undergo pre-treatment tumor biopsies",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "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": "* Has a tumor that contains an inactivating mutation, insertion, or deletion in the TP53 gene determined previously or at screening.",
            "criterions": [
                {
                    "exact_snippets": "tumor that contains an inactivating mutation, insertion, or deletion in the TP53 gene",
                    "criterion": "TP53 gene mutation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "inactivating mutation",
                                "insertion",
                                "deletion"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has a history of primary central nervous system malignancy.",
            "criterions": [
                {
                    "exact_snippets": "history of primary central nervous system malignancy",
                    "criterion": "primary central nervous system malignancy",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has gastrointestinal conditions that could affect the absorption of milademetan in the opinion of the Investigator.",
            "criterions": [
                {
                    "exact_snippets": "Has gastrointestinal conditions that could affect the absorption of milademetan",
                    "criterion": "gastrointestinal conditions",
                    "requirements": [
                        {
                            "requirement_type": "impact on absorption",
                            "expected_value": "could affect absorption of milademetan"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has an uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals, known human immunodeficiency virus infection, or active hepatitis B or C infection.",
            "criterions": [
                {
                    "exact_snippets": "uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals",
                    "criterion": "uncontrolled infection",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": [
                                "intravenous antibiotics",
                                "antivirals",
                                "antifungals"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "known human immunodeficiency virus infection",
                    "criterion": "human immunodeficiency virus infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "active hepatitis B or C infection",
                    "criterion": "hepatitis B or C infection",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has received an allogeneic bone marrow or allogeneic stem cell transplant.",
            "criterions": [
                {
                    "exact_snippets": "Has received an allogeneic bone marrow ... transplant.",
                    "criterion": "allogeneic bone marrow transplant",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Has received an ... allogeneic stem cell transplant.",
                    "criterion": "allogeneic stem cell transplant",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has a concomitant medical condition that would increase the risk of toxicity, in the opinion of the Investigator or Sponsor.",
            "criterions": [
                {
                    "exact_snippets": "Has a concomitant medical condition",
                    "criterion": "concomitant medical condition",
                    "requirements": [
                        {
                            "requirement_type": "risk of toxicity",
                            "expected_value": "increase"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with steroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 4 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment (2 weeks for stereotactic radiotherapy).",
            "criterions": [
                {
                    "exact_snippets": "clinically active brain metastases, defined as untreated and symptomatic",
                    "criterion": "clinically active brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "untreated"
                        },
                        {
                            "requirement_type": "symptom status",
                            "expected_value": "symptomatic"
                        }
                    ]
                },
                {
                    "exact_snippets": "requiring therapy with steroids or anticonvulsants to control associated symptoms",
                    "criterion": "therapy requirement for brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "therapy type",
                            "expected_value": [
                                "steroids",
                                "anticonvulsants"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Participants with treated brain metastases that are no longer symptomatic and who require no treatment with steroids",
                    "criterion": "treated brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "symptom status",
                            "expected_value": "no longer symptomatic"
                        },
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": "no treatment with steroids"
                        }
                    ]
                },
                {
                    "exact_snippets": "recovered from the acute toxic effect of radiotherapy",
                    "criterion": "recovery from radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "recovery status",
                            "expected_value": "recovered from acute toxic effect"
                        }
                    ]
                },
                {
                    "exact_snippets": "A minimum of 4 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment",
                    "criterion": "time since whole brain radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "elapsed time",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "2 weeks for stereotactic radiotherapy",
                    "criterion": "time since stereotactic radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "elapsed time",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE v4, grade ≤ 1 or baseline. Participants with chronic grade 2 toxicities may be eligible per the discretion of the Investigator and Sponsor (eg, grade 2 chemotherapy-induced neuropathy).",
            "criterions": [
                {
                    "exact_snippets": "unresolved toxicities from previous anticancer therapy",
                    "criterion": "unresolved toxicities from previous anticancer therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "toxicities (other than alopecia) not yet resolved to NCI-CTCAE v4, grade ≤ 1 or baseline",
                    "criterion": "toxicities",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 1,
                                        "unit": "grade"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Participants with chronic grade 2 toxicities may be eligible per the discretion of the Investigator and Sponsor",
                    "criterion": "chronic grade 2 toxicities",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": "discretion of the Investigator and Sponsor"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Had an autologous transplant within 3 months of starting study drug treatment.",
            "criterions": [
                {
                    "exact_snippets": "Had an autologous transplant within 3 months",
                    "criterion": "autologous transplant",
                    "requirements": [
                        {
                            "requirement_type": "time since procedure",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Is receiving concomitant treatment with a strong inducer of CYP3A.",
            "criterions": [
                {
                    "exact_snippets": "receiving concomitant treatment with a strong inducer of CYP3A",
                    "criterion": "concomitant treatment with a strong inducer of CYP3A",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Had therapeutic radiation therapy or major surgery within 4 weeks before study drug treatment or palliative radiation therapy within 2 weeks before study drug treatment.",
            "criterions": [
                {
                    "exact_snippets": "therapeutic radiation therapy ... within 4 weeks before study drug treatment",
                    "criterion": "therapeutic radiation therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "major surgery within 4 weeks before study drug treatment",
                    "criterion": "major surgery",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "palliative radiation therapy within 2 weeks before study drug treatment",
                    "criterion": "palliative radiation therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participated in a therapeutic clinical study within 3 weeks before study drug treatment, or current participation in other therapeutic investigational procedures.",
            "criterions": [
                {
                    "exact_snippets": "Participated in a therapeutic clinical study within 3 weeks before study drug treatment",
                    "criterion": "participation in therapeutic clinical study",
                    "requirements": [
                        {
                            "requirement_type": "time since participation",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "current participation in other therapeutic investigational procedures",
                    "criterion": "current participation in therapeutic investigational procedures",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prolongation of corrected QT interval by Fridericia's method (QTcF) at rest, where the mean QTcF interval is > 450 milliseconds (ms) for males and > 470 ms for females based on triplicate ECG.",
            "criterions": [
                {
                    "exact_snippets": "Prolongation of corrected QT interval by Fridericia's method (QTcF) at rest, where the mean QTcF interval is > 450 milliseconds (ms) for males",
                    "criterion": "corrected QT interval (QTcF) for males",
                    "requirements": [
                        {
                            "requirement_type": "mean interval",
                            "expected_value": {
                                "operator": ">",
                                "value": 450,
                                "unit": "milliseconds"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Prolongation of corrected QT interval by Fridericia's method (QTcF) at rest, ... > 470 ms for females",
                    "criterion": "corrected QT interval (QTcF) for females",
                    "requirements": [
                        {
                            "requirement_type": "mean interval",
                            "expected_value": {
                                "operator": ">",
                                "value": 470,
                                "unit": "milliseconds"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant or breastfeeding.",
            "criterions": [
                {
                    "exact_snippets": "Pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "breastfeeding",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Substance abuse or medical, psychological, or social conditions that, in the opinion of the Investigator, may interfere with the participant's participation in the clinical study or evaluation of the clinical study results.",
            "criterions": [
                {
                    "exact_snippets": "Substance abuse",
                    "criterion": "substance abuse",
                    "requirements": [
                        {
                            "requirement_type": "interference with participation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "medical, psychological, or social conditions",
                    "criterion": "medical, psychological, or social conditions",
                    "requirements": [
                        {
                            "requirement_type": "interference with participation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior treatment with an MDM2 inhibitor.",
            "criterions": [
                {
                    "exact_snippets": "Prior treatment with an MDM2 inhibitor",
                    "criterion": "MDM2 inhibitor treatment",
                    "requirements": [
                        {
                            "requirement_type": "prior treatment",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [
        {
            "line": "* Had systemic treatment with anticancer therapy, antibody-based therapy, retinoid therapy, or hormonal therapy within 3 weeks before study drug treatment; or treatment with nitrosoureas or mitomycin C within 6 weeks before study drug treatment; or treatment with small-molecule targeted agents within 2 weeks before study drug treatment. Previous and concurrent use of hormone replacement therapy, the use of gonadotropin releasing hormone modulators for prostate cancer, and the use of somatostatin analogs for neuroendocrine tumors are permitted if such therapy has not been changed within 8 weeks before study drug treatment.",
            "criterions": [
                {
                    "exact_snippets": "Had systemic treatment with anticancer therapy ... within 3 weeks before study drug treatment",
                    "criterion": "systemic anticancer therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "antibody-based therapy ... within 3 weeks before study drug treatment",
                    "criterion": "antibody-based therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "retinoid therapy ... within 3 weeks before study drug treatment",
                    "criterion": "retinoid therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "hormonal therapy within 3 weeks before study drug treatment",
                    "criterion": "hormonal therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "treatment with nitrosoureas ... within 6 weeks before study drug treatment",
                    "criterion": "nitrosoureas treatment",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "treatment with mitomycin C within 6 weeks before study drug treatment",
                    "criterion": "mitomycin C treatment",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "treatment with small-molecule targeted agents within 2 weeks before study drug treatment",
                    "criterion": "small-molecule targeted agents",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Previous and concurrent use of hormone replacement therapy ... are permitted if such therapy has not been changed within 8 weeks before study drug treatment",
                    "criterion": "hormone replacement therapy",
                    "requirements": [
                        {
                            "requirement_type": "therapy change",
                            "expected_value": {
                                "operator": ">=",
                                "value": 8,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "the use of gonadotropin releasing hormone modulators for prostate cancer ... are permitted if such therapy has not been changed within 8 weeks before study drug treatment",
                    "criterion": "gonadotropin releasing hormone modulators for prostate cancer",
                    "requirements": [
                        {
                            "requirement_type": "therapy change",
                            "expected_value": {
                                "operator": ">=",
                                "value": 8,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "the use of somatostatin analogs for neuroendocrine tumors ... are permitted if such therapy has not been changed within 8 weeks before study drug treatment",
                    "criterion": "somatostatin analogs for neuroendocrine tumors",
                    "requirements": [
                        {
                            "requirement_type": "therapy change",
                            "expected_value": {
                                "operator": ">=",
                                "value": 8,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "failed_miscellaneous": []
}