Targeted Radionuclide Therapy for Metastatic Melanoma [131I] ICF01012: Phase I Study
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Evaluation of the recommended therapeutic dose of [131I] ICF01012
研究概览
简要总结
This study is a phase I clinical trial aimed to determine the recommended dose of [131I]ICF01012 to administer for the treatment of patients with pigmented metastatic melanoma (binding [131I]ICF01012 ). The [131I]ICF01012 is a targeted radionuclide therapy with a high affinity for melanin.
详细描述
This study will include a maximum of 36 patients. This study will begin with a preselection part that consists of an injection of [131I]ICF01012 at a diagnostic dose (185 MBq) in order to preselect patients who will receive the therapeutic dose according to the dosimetry results : binding of [131I]ICF01012 on at least a tumoral lesion and an acceptable radiation absorbed dose to major organs.
The second phase will consist of a therapeutic part with a single administration of [131I]ICF01012 at a therapeutic dose. This part is a dose escalation model (4 levels of therapeutic dose were tested)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient with metastatic melanoma failure to recommended treatments by HAS.
- •Initial histological diagnosis of cutaneous melanoma pigmented or unknown status or choroidal melanoma.
- •Presence of at least one measurable lesion and / or evaluable in 18FDG-PET as PERCIST criteria.
- •Presence of at least one measurable lesion and / or evaluable as CT RECIST 1.1 criteria.
- •WHO performance index ≤ 2 .
- •Age> 18 years
- •Life expectancy> 3 months.
- •Creatinine ≤ 1,5 x ULN or creatinine clearance ≥ 60ml/min if creatinine > 1,5 x ULN , Neutrophil > 1,5.109L-1, Platellets > 100 x 109L-1, prothrombine time < 1,3 x control, Hemoglobin > 9 g/dL, facteur V > 80% (or AST, ALT ≤ 3 x LNS (≤ 5 x ULN if liver metastasis)).
- •Normal cardiac fonction (LVEF> 40%).
排除标准
- •Brain metastases symptomatic
- •Patient with a VI skin phototype
- •Previous treatment with chemotherapy, radiotherapy, immunotherapy and targeted therapy in the previous 4 weeks, the first injection of [131I] ICF01012
- •Pregnant woman, nursing or woman of childbearing age refusing to follow effective contraception during treatment and 12 months after the administration of therapeutic dose.
- •Men refusing to follow effective contraception during treatment and 12 months after the administration of therapeutic dose
- •Other evolutionary known cancer in the past five years
- •Earlier irradiation of more than 25% of the bone marrow
- •Suspicion of invasion of more than 25% of the bone marrow on imaging 18F-FDG PET-CT
- •External Radiotherapy on target organs or the maximum dose as recommended in force
- •Uncontrolled diabetes
- •Known history of allergy to the excipients of the solution of [131I]ICF01012
- •Any comorbidity or severe disease at the discretion of the investigator
研究组 & 干预措施
therapeutic dose activity (level 1)
[131]ICF01012 at a therapeutic dose of 800 MBq/m² , single dose at D11 (intravenous administration)
干预措施: [131I]ICF01012 (therapeutic dose level 1) (Drug)
therapeutic dose activity (level 2)
[131]ICF01012 at a therapeutic dose of 1600 MBq/m² , single dose at D11 (intravenous administration)
干预措施: [131I]ICF01012 (therapeutic dose level 2) (Drug)
therapeutic dose activity (level 3)
[131]ICF01012 at a therapeutic dose of 2700 MBq/m² , single dose at D11 (intravenous administration)
干预措施: [131I]ICF01012 (therapeutic dose level 3) (Drug)
therapeutic dose activity (level 4)
[131]ICF01012 at a therapeutic dose of 4000 MBq/m² , single dose at D11 (intravenous administration)
干预措施: [131I]ICF01012 (therapeutic dose level 4) (Drug)
结局指标
主要结局
Evaluation of the recommended therapeutic dose of [131I] ICF01012
时间窗: Only toxicities observed during the 6 weeks following administration of the therapeutic dose will be considered for the evaluation of DLT
defined as the highest dose at which the percentage of DLT (dose limiting toxicity) is less than 33%. The DLT is defined as: * all non hematologic toxicities NCI-CTC grade 3-4 except for alopecia, nausea, vomiting and fever that can be controlled by appropriate measures. * hematologic toxicities as thrombopenia and anemia of grade 4, neutropenia of grade 4 for more than 5 days, thrombopenia of grade 3 with bleeding and all other hematologic toxicities of grade 3 clinically significant of more than 3 weeks
次要结局
- Evaluation of the sensitivity and specificity by patients and by lesions of [131I]ICF01012 ICF01012 for the visualization of metastatic melanoma lesions from the examinations made during the selection phase(selection phase Day 0 - Day 7)
- Evaluation of the tolerance of [131I] ICF01012 (adverse events assessed by NCI-CTC Version 4.03)(from the the first dose to the end of study (3 months after diagnostic dose))
- Pharmacokinetics of [131I] ICF01012 including the study of biodistribution and excretion (radiation counting of serum, whole blood and urinary samples)(selection phase Day 0 (diagnostic dose), Day 1, and Day 4, Day 7)
- Evaluation of the therapeutic response of [131I] ICF01012.(at 3 months)
- Evaluation of personal dosimetry for the administration of [131I]ICF01012.(Selection phase : Day 0, Day 1, Day 4, and Day 7; therapeutic phase : Day 15, Day 18 and Day 25, Day 74)