Targeted Radionuclide Therapy for Metastatic Melanoma [131I] ICF01012 (MELRIV-1)

Targeted Radionuclide Therapy for Metastatic Melanoma [131I] ICF01012: Phase I Study

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.

Study Overview

• Status: Recruiting
• Conditions: Melanoma
• Intervention / Treatment: Drug: [131I]ICF01012 (therapeutic dose level 1); Drug: [131I]ICF01012 (therapeutic dose level 2); Drug: [131I]ICF01012 (therapeutic dose level 3); Drug: [131I]ICF01012 (therapeutic dose level 4)

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)

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France
    • Recruiting
    • CHU Clermont-Ferrand
  • Clermont-Ferrand, France
    • Recruiting
    • Centre Jean Perrin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: therapeutic dose activity (level 1); [131]ICF01012 at a therapeutic dose of 800 MBq/m² , single dose at D11 (intravenous administration)	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
EXPERIMENTAL: therapeutic dose activity (level 2); [131]ICF01012 at a therapeutic dose of 1600 MBq/m² , single dose at D11 (intravenous administration)	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
EXPERIMENTAL: therapeutic dose activity (level 3); [131]ICF01012 at a therapeutic dose of 2700 MBq/m² , single dose at D11 (intravenous administration)	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
EXPERIMENTAL: therapeutic dose activity (level 4); [131]ICF01012 at a therapeutic dose of 4000 MBq/m² , single dose at D11 (intravenous administration)	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the recommended therapeutic dose of [131I] ICF01012	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	Only toxicities observed during the 6 weeks following administration of the therapeutic dose will be considered for the evaluation of DLT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	binding of [131I]ICF01012 compared to standard evaluation of metastatic lesion (standard imaging (CT Scan, TEP ...) or clinical evaluation)	selection phase Day 0 - Day 7
Evaluation of the tolerance of [131I] ICF01012 (adverse events assessed by NCI-CTC Version 4.03)	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)	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.	Response will be categorized according to the criteria from RECIST 1.1 and PERCIST criteria: complete response, partial response, stable disease and progressive disease	at 3 months
Evaluation of personal dosimetry for the administration of [131I]ICF01012.	assessed by whole-body planar studies and tomographic imaging with single-photon emission computed tomography (SPECT)/CT	Selection phase : Day 0, Day 1, Day 4, and Day 7; therapeutic phase : Day 15, Day 18 and Day 25, Day 74

Collaborators and Investigators

• Sponsor: Centre Jean Perrin

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 18, 2019
• Primary Completion (ANTICIPATED): October 1, 2024
• Study Completion (ANTICIPATED): November 1, 2024

Study Registration Dates

• First Submitted: December 18, 2018
• First Submitted That Met QC Criteria: December 21, 2018
• First Posted (ACTUAL): December 24, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 3, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: metastatic melanoma; targeted radionuclide therapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: 2016-002444-17; TRANSLA12-143 (OTHER_GRANT: Ministry of Health, National Cancer Institute, France)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No