Clinical trial NCT03784625: Targeted Radionuclide Therapy for Metastatic Melanoma [131I] ICF01012
Official title: Targeted Radionuclide Therapy for Metastatic Melanoma [131I] ICF01012: Phase I Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Melanoma
Keywords: metastatic melanoma
targeted radionuclide therapy
Lead sponsor: Centre Jean Perrin
Sponsor class: OTHER
First posted: 2018-12-24
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: dose escalation model
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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)

Eligibility criteria: Inclusion Criteria:

* 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\&gt; 18 years
* Life expectancy\&gt; 3 months.
* Creatinine ≤ 1,5 x ULN or creatinine clearance ≥ 60ml/min if creatinine \&gt; 1,5 x ULN , Neutrophil \&gt; 1,5.109L-1, Platellets \&gt; 100 x 109L-1, prothrombine time \&lt; 1,3 x control, Hemoglobin \&gt; 9 g/dL, facteur V \&gt; 80% (or AST, ALT ≤ 3 x LNS (≤ 5 x ULN if liver metastasis)).
* Normal cardiac fonction (LVEF\&gt; 40%).

Exclusion Criteria:

* 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

Primary outcomes:
measure: Evaluation of the recommended therapeutic dose of [131I] ICF01012
timeFrame: Only toxicities observed during the 6 weeks following administration of the therapeutic dose will be considered for the evaluation of DLT
Secondary outcomes:
measure: 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
timeFrame: selection phase Day 0 - Day 7
measure: Evaluation of the tolerance of [131I] ICF01012 (adverse events assessed by NCI-CTC Version 4.03)
timeFrame: from the the first dose to the end of study (3 months after diagnostic dose)
measure: Pharmacokinetics of [131I] ICF01012 including the study of biodistribution and excretion (radiation counting of serum, whole blood and urinary samples)
timeFrame: selection phase Day 0 (diagnostic dose), Day 1, and Day 4, Day 7
measure: Evaluation of the therapeutic response of [131I] ICF01012.
timeFrame: at 3 months
measure: Evaluation of personal dosimetry for the administration of [131I]ICF01012.
timeFrame: Selection phase : Day 0, Day 1, Day 4, and Day 7; therapeutic phase : Day 15, Day 18 and Day 25, Day 74
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
Study officials:
affiliation: Centre Jean Perrin
name: Florent CACHIN, Pr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Thivat E, Rouanet J, Auzeloux P, Sas N, Jouberton E, Levesque S, Billoux T, Mansard S, Molnar I, Chanchou M, Fois G, Maigne L, Chezal JM, Miot-Noirault E, D'Incan M, Durando X, Cachin F. Phase I study of [131I] ICF01012, a targeted radionuclide therapy, in metastatic melanoma: MELRIV-1 protocol. BMC Cancer. 2022 Apr 15;22(1):417. doi: 10.1186/s12885-022-09495-3.