Melanoma
Conditions
Keywords
metastatic melanoma, targeted radionuclide therapy
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)
Interventions
DRUG[131I]ICF01012 (therapeutic dose level 1)
* 1 diagnostic injection (D0) at a diagnostic dose of 185 MBq. This first dose permits to pre-select patients who will received a therapeutic dose according to the dosimetry results ( binding on at least a tumoral lesion, an acceptable radiation absorbed dose to major organs) * 1 therapeutic injection (D11) at a dose of 800 MBq/m²
DRUG[131I]ICF01012 (therapeutic dose level 2)
* 1 diagnostic injection (D0) at a diagnostic dose of 185 MBq. This first dose permits to pre-select patients who will received a therapeutic dose according to the dosimetry results ( binding on at least a tumoral lesion, an acceptable radiation absorbed dose to major organs) * 1 therapeutic injection (D11) at a dose of 1600 MBq/m²
DRUG[131I]ICF01012 (therapeutic dose level 3)
* 1 diagnostic injection (D0) at a diagnostic dose of 185 MBq. This first dose permits to pre-select patients who will received a therapeutic dose according to the dosimetry results ( binding on at least a tumoral lesion, and an acceptable radiation absorbed dose to major organs) * 1 therapeutic injection (D11) at a dose of 2700 MBq/m²
DRUG[131I]ICF01012 (therapeutic dose level 4)
* 1 diagnostic injection (D0) at a diagnostic dose of 185 MBq. This first dose permits to pre-select patients who will received a therapeutic dose according to the dosimetry results ( binding on at least a tumoral lesion, and an acceptable radiation absorbed dose to major organs) * 1 therapeutic injection (D11) at a dose of 4000 MBq/m²
Sponsors
Centre Jean Perrin
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
dose escalation model
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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> 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%).
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the recommended therapeutic dose of [131I] ICF01012 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | binding of \[131I\]ICF01012 compared to standard evaluation of metastatic lesion (standard imaging (CT Scan, TEP ...) or clinical evaluation) |
| 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) | adverse events assessed by NCI-CTC Version 4.03 |
| 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 | radiation counting of serum, whole blood and urinary samples |
| Evaluation of the therapeutic response of [131I] ICF01012. | at 3 months | Response will be categorized according to the criteria from RECIST 1.1 and PERCIST criteria: complete response, partial response, stable disease and progressive disease |
| 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 | assessed by whole-body planar studies and tomographic imaging with single-photon emission computed tomography (SPECT)/CT |
Countries
France
Outcome results
None listed