We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Phase I study of [<sup>131</sup>I] ICF01012, a targeted radionuclide therapy, in metastatic melanoma: MELRIV-1 protocol.
- Authors
Thivat, Emilie; Rouanet, Jacques; Auzeloux, Philippe; Sas, Nicolas; Jouberton, Elodie; Levesque, Sophie; Billoux, Tommy; Mansard, Sandrine; Molnar, Ioana; Chanchou, Marion; Fois, Giovanna; Maigne, Lydia; Chezal, Jean-Michel; Miot-Noirault, Elisabeth; D'Incan, Michel; Durando, Xavier; Cachin, Florent
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Discussion: </bold>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.<bold>Trial Registration: </bold>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.
- Subjects
RADIOISOTOPES; INTRAVENOUS injections; METASTASIS; TREATMENT effectiveness; ANIMAL models in research; MELANOMA
- Publication
BMC Cancer, 2022, Vol 22, Issue 1, p1
- ISSN
1471-2407
- Publication type
journal article
- DOI
10.1186/s12885-022-09495-3