背景:首先开发了靶向黑色素的基于苯甲酰胺的放射性配体用于黑色素瘤成像,然后用于靶向放射性核素治疗(TRT)的治疗目的。[131I]ICF01012为治疗提供了非常有利的体内药代动力学特征。已经在黑色素瘤的临床前模型中建立了肿瘤生长减少和存活增加。根据这些临床前结果,我们启动了一项首次人体试验,旨在确定[131I]ICF01012用于治疗色素性转移性黑色素瘤患者的推荐剂量.
方法:MELRIV-1试验是一个开放标签,多中心,剂量递增I期试验。这项研究分为两个步骤,选择部分,IV注射低活性的[131I]ICF01012(D0时为185MBq),以选择治疗部分可能受益于[131I]ICF01012TRT的患者,即患者表现出至少一个具有[131I]ICF01012摄取的肿瘤病变和对关键器官的可接受的个性化剂量测定(肝脏,肾,肺和视网膜)。根据持续重新评估方法(CRM)设计驱动的剂量递增方案,800MBq/m2,或1600MBq/m2,或2700MBq/m2或4000MBq/m2的[131I]ICF01012的单次治疗性注射将在D11(±4天)施用。主要终点是[131I]ICF01012的推荐治疗剂量,DLT定义为治疗剂量后6周内的任何3-4级NCI-CT毒性。安全,药代动力学,生物分布(使用平面全身和SPECT-CT采集),[131I]ICF01012的敏感性/特异性和治疗效果将作为次要目标进行评估。接受治疗性注射的患者将随访至TRT后3个月。由于治疗部分需要6至18名患者,选择部分将招募多达36名患者。
结论:这项研究是一项首次人体试验,评估[131I]ICF01012TRT在转移性恶性黑素瘤中的诊断剂量[131I]ICF01012,以选择可能受益于治疗剂量[131I]ICF01012的患者,至少一个肿瘤病变具有[131I]ICF01012健康的AD摄取。
背景:Clinicaltrials.gov:NCT03784625。2018年12月24日注册。法国国家药品和健康产品安全局(ANSM)的标识符:N°EudraCT2016-002444-17。
BACKGROUND: Benzamide-based radioligands targeting melanin were first developed for imaging melanoma and then for therapeutic purpose with targeted radionuclide therapy (TRT). [131I]ICF01012 presents a highly favorable pharmacokinetics profile in vivo for therapy. Tumour growth reduction and increase survival have been established in preclinical models of melanoma. According the these preclinical results, we initiate a first-in-human
study aimed to determine the recommended dose of [131I]ICF01012 to administer for the treatment of patients with pigmented metastatic melanoma.
METHODS: The MELRIV-1
trial is an open-label, multicentric, dose-escalation phase I
trial. The
study is divided in 2 steps, a selection part with an IV injection of low activity of [131I]ICF01012 (185 MBq at D0) to select patients who might benefit from [131I]ICF01012 TRT in therapeutic part, i.e. patient presenting at least one tumour lesion with [131I]ICF01012 uptake and an acceptable personalized dosimetry to critical organs (liver, kidney, lung and retina). According to dose escalation scheme driven by a Continual Reassessment Method (CRM) design, a single therapeutic injection of 800 MBq/m2, or 1600 MBq/m2, or 2700 MBq/m2 or 4000 MBq/m2 of [131I]ICF01012 will be administered at D11 (± 4 days). The primary endpoint is the recommended therapeutic dose of [131I]ICF01012, with DLT defined as any grade 3-4 NCI-CT toxicity during the 6 weeks following therapeutic dose. Safety, pharmacokinetic, biodistribution (using planar whole body and SPECT-CT acquisitions), sensitivity / specificity of [131I]ICF01012, and therapeutic efficacy will be assessed as secondary objectives. Patients who received therapeutic injection will be followed until 3 months after TRT. Since 6 to 18 patients are needed for the therapeutic part, up to 36 patients will be enrolled in the selection part.
CONCLUSIONS: This
study is a first-in-human
trial evaluating the [131I]ICF01012 TRT in metastatic malignant melanomas with a diagnostic dose of the [131I]ICF01012 to select the patients who may benefit from a therapeutic dose of [131I]ICF01012, with at least one tumor lesion with [131I]ICF01012 uptake and an acceptable AD to healthy organ.
BACKGROUND: Clinicaltrials.gov : NCT03784625 . Registered on December 24, 2018. Identifier in French National Agency for the Safety of Medicines and Health Products (ANSM): N°EudraCT 2016-002444-17.