{
    "info": {
        "nct_id": "NCT06870994",
        "official_title": "Intra-tumoral Targeted Hyperthermic Therapy (THT) for Stage 3C/3D/4M1 Cutaneous Metastatic Melanoma in Patients With Targetable Cutaneous and/or Sub-cutaneous Tumors",
        "inclusion_criteria": "1. 16 years of age or older;\n2. Participants with histologically or cytologically confirmed stage 3C/3D/4M1 advanced or cutaneous metastatic melanoma, with measurable disease by iRECIST 1.1 criteria, including any number of cutaneous lesions;\n3. Present a visible and accessible primary tumor or metastatic deposit (any site) that has not been surgically removed;\n4. Present target tumors of ≤2.5 cm in diameter;\n5. Participants must have received and failed systemic and local intra-tumoral therapy at least one prior standard therapy, including immune checkpoint inhibitors (e.g., anti- PD1 or anti-CTLA-4), and failed local intra-tumoral IL-2 treatment. Failed response to treatment will be categorized according to iRECIST guidelines. Patients who have: a) Immune partial response (iPR): At least a 30% decrease in the sum of diameters of target lesions compared to baseline, no progression of non-target lesions, No new lesions; or b) Immune Stable Disease (iSD): Neither sufficient reduction to qualify for iPR nor sufficient increase to qualify for iCPD (immune confirmed progressive disease), no new lesions; or c) Immune Unconfirmed Progressive Disease (iUPD): At least a 20% increase in the sum of diameters of target lesions, taking the smallest sum on study as the reference, appearance of new lesions, iUPD needs confirmation after at least 4 weeks; if confirmed, it becomes iCPD; or d) Immune Confirmed Progressive Disease (iCPD): iUPD must be confirmed in a follow-up assessment (minimum of 4 weeks after initial iUPD), if progressive disease (increase in lesion size or additional new lesions) is still evident upon re-evaluation, iCPD is confirmed.\n6. Participants must agree to discontinue treatment with local intralesional immunotherapies during the study, with resumption after completion of the trial;\n7. ECOG Performance Status: ≤1;\n8. Life expectancy: ≥6 months;\n9. Participants able and willing to provide written informed consent and comply with the trial protocol.\n10. Either BRAF positive (BRAF+) or BRAF negative (BRAF-).\n\nExclusion criteria:\n\n1. Women who are pregnant, breastfeeding, or planning to become pregnant during the study. Women of childbearing potential must have a negative pregnancy test within 72 hours prior to enrollment and agree to use adequate contraception throughout the study;\n2. Any infection requiring systemic therapy or other concurrent medical conditions (e.g., hepatitis B, hepatitis C, HIV) that would interfere with the study;\n3. Myocardial infarction or stroke within the past 6 months, uncontrolled angina, or significant arrhythmia;\n4. Participants receiving blood thinners as part of therapeutic anticoagulation therapy;\n5. Any severe or uncontrolled comorbid condition that, in the investigator's opinion, would pose excessive risk to the participants (e.g., immunodeficiencies, severe hypertension, uncontrolled diabetes, liver failure);\n6. Participation in another clinical trial involving an investigational product/device within 30 days prior to screening;\n7. Any condition that would impede compliance with study procedures;\n8. Participants with a known allergy to gold of any kind;\n9. Participants who are unable to tolerate cutaneous injections for any reason will not be eligible;\n10. Participants with a known allergy to injectable local analgesics;\n11. Participants with ocular melanoma or melanoma involving periorbital skin.\nHealthy volunteers allowed\nMust have minimum age of 16 Years",
        "exclusion_criteria": "",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. 16 years of age or older;",
            "criterions": [
                {
                    "exact_snippets": "16 years of age or older",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "N/A",
                            "expected_value": {
                                "operator": ">=",
                                "value": 16,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Participants with histologically or cytologically confirmed stage 3C/3D/4M1 advanced or cutaneous metastatic melanoma, with measurable disease by iRECIST 1.1 criteria, including any number of cutaneous lesions;",
            "criterions": [
                {
                    "exact_snippets": "histologically or cytologically confirmed",
                    "criterion": "confirmation method",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "stage 3C/3D/4M1 advanced or cutaneous metastatic melanoma",
                    "criterion": "melanoma stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "3C",
                                "3D",
                                "4M1"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "measurable disease by iRECIST 1.1 criteria",
                    "criterion": "measurable disease",
                    "requirements": [
                        {
                            "requirement_type": "criteria",
                            "expected_value": "iRECIST 1.1"
                        }
                    ]
                },
                {
                    "exact_snippets": "including any number of cutaneous lesions",
                    "criterion": "cutaneous lesions",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": "any number"
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Present a visible and accessible primary tumor or metastatic deposit (any site) that has not been surgically removed;",
            "criterions": [
                {
                    "exact_snippets": "visible and accessible primary tumor or metastatic deposit",
                    "criterion": "primary tumor or metastatic deposit",
                    "requirements": [
                        {
                            "requirement_type": "visibility",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "accessibility",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "has not been surgically removed",
                    "criterion": "surgical removal",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "not removed"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Present target tumors of ≤2.5 cm in diameter;",
            "criterions": [
                {
                    "exact_snippets": "target tumors of ≤2.5 cm in diameter",
                    "criterion": "target tumor size",
                    "requirements": [
                        {
                            "requirement_type": "size",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "cm"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Participants must have received and failed systemic and local intra-tumoral therapy at least one prior standard therapy, including immune checkpoint inhibitors (e.g., anti- PD1 or anti-CTLA-4), and failed local intra-tumoral IL-2 treatment. Failed response to treatment will be categorized according to iRECIST guidelines. Patients who have: a) Immune partial response (iPR): At least a 30% decrease in the sum of diameters of target lesions compared to baseline, no progression of non-target lesions, No new lesions; or b) Immune Stable Disease (iSD): Neither sufficient reduction to qualify for iPR nor sufficient increase to qualify for iCPD (immune confirmed progressive disease), no new lesions; or c) Immune Unconfirmed Progressive Disease (iUPD): At least a 20% increase in the sum of diameters of target lesions, taking the smallest sum on study as the reference, appearance of new lesions, iUPD needs confirmation after at least 4 weeks; if confirmed, it becomes iCPD; or d) Immune Confirmed Progressive Disease (iCPD): iUPD must be confirmed in a follow-up assessment (minimum of 4 weeks after initial iUPD), if progressive disease (increase in lesion size or additional new lesions) is still evident upon re-evaluation, iCPD is confirmed.",
            "criterions": [
                {
                    "exact_snippets": "Participants must have received and failed systemic and local intra-tumoral therapy",
                    "criterion": "systemic and local intra-tumoral therapy",
                    "requirements": [
                        {
                            "requirement_type": "failure",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "at least one prior standard therapy, including immune checkpoint inhibitors (e.g., anti- PD1 or anti-CTLA-4)",
                    "criterion": "prior standard therapy",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "therapy"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "failed local intra-tumoral IL-2 treatment",
                    "criterion": "local intra-tumoral IL-2 treatment",
                    "requirements": [
                        {
                            "requirement_type": "failure",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Immune partial response (iPR): At least a 30% decrease in the sum of diameters of target lesions compared to baseline",
                    "criterion": "immune partial response (iPR)",
                    "requirements": [
                        {
                            "requirement_type": "decrease in target lesion size",
                            "expected_value": {
                                "operator": ">=",
                                "value": 30,
                                "unit": "%"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Immune Stable Disease (iSD): Neither sufficient reduction to qualify for iPR nor sufficient increase to qualify for iCPD (immune confirmed progressive disease)",
                    "criterion": "immune stable disease (iSD)",
                    "requirements": [
                        {
                            "requirement_type": "reduction in target lesion size",
                            "expected_value": "not sufficient for iPR"
                        },
                        {
                            "requirement_type": "increase in target lesion size",
                            "expected_value": "not sufficient for iCPD"
                        }
                    ]
                },
                {
                    "exact_snippets": "Immune Unconfirmed Progressive Disease (iUPD): At least a 20% increase in the sum of diameters of target lesions",
                    "criterion": "immune unconfirmed progressive disease (iUPD)",
                    "requirements": [
                        {
                            "requirement_type": "increase in target lesion size",
                            "expected_value": {
                                "operator": ">=",
                                "value": 20,
                                "unit": "%"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Immune Confirmed Progressive Disease (iCPD): iUPD must be confirmed in a follow-up assessment (minimum of 4 weeks after initial iUPD)",
                    "criterion": "immune confirmed progressive disease (iCPD)",
                    "requirements": [
                        {
                            "requirement_type": "confirmation of iUPD",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time after initial iUPD",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Participants must agree to discontinue treatment with local intralesional immunotherapies during the study, with resumption after completion of the trial;",
            "criterions": [
                {
                    "exact_snippets": "discontinue treatment with local intralesional immunotherapies during the study",
                    "criterion": "treatment with local intralesional immunotherapies",
                    "requirements": [
                        {
                            "requirement_type": "discontinuation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. ECOG Performance Status: ≤1;",
            "criterions": [
                {
                    "exact_snippets": "ECOG Performance Status: ≤1",
                    "criterion": "ECOG Performance Status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Life expectancy: ≥6 months;",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy: ≥6 months;",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Participants able and willing to provide written informed consent and comply with the trial protocol.",
            "criterions": [
                {
                    "exact_snippets": "able and willing to provide written informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "comply with the trial protocol",
                    "criterion": "compliance with trial protocol",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Either BRAF positive (BRAF+) or BRAF negative (BRAF-).",
            "criterions": [
                {
                    "exact_snippets": "BRAF positive (BRAF+)",
                    "criterion": "BRAF status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "BRAF negative (BRAF-)",
                    "criterion": "BRAF status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "negative"
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Women who are pregnant, breastfeeding, or planning to become pregnant during the study. Women of childbearing potential must have a negative pregnancy test within 72 hours prior to enrollment and agree to use adequate contraception throughout the study;",
            "criterions": [
                {
                    "exact_snippets": "Women who are pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "breastfeeding",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "planning to become pregnant during the study",
                    "criterion": "pregnancy planning",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Women of childbearing potential must have a negative pregnancy test within 72 hours prior to enrollment",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        },
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 72 hours prior to enrollment"
                        }
                    ]
                },
                {
                    "exact_snippets": "agree to use adequate contraception throughout the study",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Any infection requiring systemic therapy or other concurrent medical conditions (e.g., hepatitis B, hepatitis C, HIV) that would interfere with the study;",
            "criterions": [
                {
                    "exact_snippets": "Any infection requiring systemic therapy",
                    "criterion": "infection",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "systemic therapy"
                        }
                    ]
                },
                {
                    "exact_snippets": "other concurrent medical conditions (e.g., hepatitis B, hepatitis C, HIV)",
                    "criterion": "concurrent medical conditions",
                    "requirements": [
                        {
                            "requirement_type": "examples",
                            "expected_value": [
                                "hepatitis B",
                                "hepatitis C",
                                "HIV"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Myocardial infarction or stroke within the past 6 months, uncontrolled angina, or significant arrhythmia;",
            "criterions": [
                {
                    "exact_snippets": "Myocardial infarction ... within the past 6 months",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "stroke within the past 6 months",
                    "criterion": "stroke",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled angina",
                    "criterion": "angina",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "uncontrolled"
                        }
                    ]
                },
                {
                    "exact_snippets": "significant arrhythmia",
                    "criterion": "arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "significant"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Participants receiving blood thinners as part of therapeutic anticoagulation therapy;",
            "criterions": [
                {
                    "exact_snippets": "Participants receiving blood thinners as part of therapeutic anticoagulation therapy",
                    "criterion": "blood thinners",
                    "requirements": [
                        {
                            "requirement_type": "usage",
                            "expected_value": "therapeutic anticoagulation therapy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Any severe or uncontrolled comorbid condition that, in the investigator's opinion, would pose excessive risk to the participants (e.g., immunodeficiencies, severe hypertension, uncontrolled diabetes, liver failure);",
            "criterions": [
                {
                    "exact_snippets": "severe or uncontrolled comorbid condition ... immunodeficiencies",
                    "criterion": "immunodeficiencies",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        },
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "severe or uncontrolled comorbid condition ... severe hypertension",
                    "criterion": "hypertension",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        },
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "severe or uncontrolled comorbid condition ... uncontrolled diabetes",
                    "criterion": "diabetes",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "severe or uncontrolled comorbid condition ... liver failure",
                    "criterion": "liver failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Participation in another clinical trial involving an investigational product/device within 30 days prior to screening;",
            "criterions": [
                {
                    "exact_snippets": "Participation in another clinical trial",
                    "criterion": "participation in another clinical trial",
                    "requirements": [
                        {
                            "requirement_type": "time since last participation",
                            "expected_value": {
                                "operator": "<",
                                "value": 30,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Any condition that would impede compliance with study procedures;",
            "criterions": [
                {
                    "exact_snippets": "Any condition that would impede compliance with study procedures",
                    "criterion": "condition affecting compliance",
                    "requirements": [
                        {
                            "requirement_type": "impact",
                            "expected_value": "impede compliance with study procedures"
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Participants with a known allergy to gold of any kind;",
            "criterions": [
                {
                    "exact_snippets": "known allergy to gold",
                    "criterion": "allergy to gold",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Participants who are unable to tolerate cutaneous injections for any reason will not be eligible;",
            "criterions": [
                {
                    "exact_snippets": "unable to tolerate cutaneous injections",
                    "criterion": "cutaneous injection tolerance",
                    "requirements": [
                        {
                            "requirement_type": "tolerance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Participants with a known allergy to injectable local analgesics;",
            "criterions": [
                {
                    "exact_snippets": "known allergy to injectable local analgesics",
                    "criterion": "allergy to injectable local analgesics",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Participants with ocular melanoma or melanoma involving periorbital skin.",
            "criterions": [
                {
                    "exact_snippets": "ocular melanoma",
                    "criterion": "ocular melanoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "melanoma involving periorbital skin",
                    "criterion": "melanoma involving periorbital skin",
                    "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 16 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 16 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 16,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "Exclusion criteria:",
            "criterions": []
        }
    ],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}