Targeted Alpha Particle Radiotherapy for Metastatic Uveal Melanoma
First in Human Phase I Study of 225Actinium-MTI-201 (225Ac-MTI-201) in Metastatic Uveal Melanoma
2 other identifiers
interventional
16
1 country
1
Brief Summary
The primary aim of the study is to establish the maximum-tolerated dose (MTD) of 225Ac-MTI-201 in participants with metastatic uveal melanoma. The secondary aims are to describe the pharmacokinetics of 225Ac-MTI-201 and the toxic effects of 225Ac-MTI-201 in participants with metastatic uveal melanoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jul 2022
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 21, 2022
CompletedFirst Submitted
Initial submission to the registry
August 9, 2022
CompletedFirst Posted
Study publicly available on registry
August 11, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
February 25, 2029
ExpectedOctober 30, 2025
October 1, 2025
3.7 years
August 9, 2022
October 28, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Maximum Tolerated Dose (MTD) of 225Ac-MTI-201
MTD will be determined by testing increasing doses up to 1327 microCi of 225Ac-MTI-201, administered as a single dose via IV on dose escalation cohorts 1 to 12 with 1 to 6 participants each. The MTD is reached when 6 patients receive the same highest tolerated dose of 225Ac-MTI-201. If dose-limiting toxicity (DLT) consistently occurs at the next higher dose of 225Ac-MTI-201, then 5 additional doses at the previous dose of 225Ac-MTI-201 will mark the end of clinical trial.
Within 4 weeks after study drug administration
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
The following will constitute a DLT if the occurrence was within 4 weeks post-dose: 1. Any death not due to the underlying disease or extraneous cause 2. Absolute neutrophil count \< 0.5 X 10\^9/L or the development of febrile neutropenia. 3. Grade 3 thrombocytopenia with significant bleeding, or any Grade 4 thrombocytopenia. 4. Laboratory abnormalities that satisfy Hy's law i.e., ALT or AST elevation \> 3X ULN, total bilirubin elevation \> 2X ULN, absence of initial findings of cholestasis, and no other reason can be found to explain the combination of increased ALT/AST and total bilirubin 5. Any grade 3 or higher non-hematological toxicity possibly, probably, or definitely attributed to the study drug with the following exceptions: 1) Grade 3 nausea, vomiting or diarrhea (less than 72 hours with care). 2) Grade 3 fatigue (less than 1 week). 3) Grade \> 3 electrolyte abnormalities (less than 48 hours), not clinically complicated, and resolves with or without medical interventions
Within 4 weeks after study drug administration
The Number of Participants Who Experienced Serious or Non-Serious Adverse Events
Vital signs, physical examination, 12-lead EKG, and blood including toxicity on Days 8, 15, 22, and 29: Week 9, Follow-Up (Starting in Week 17) Adverse Event (AE), any new untoward medical occurrence or worsening of a preexisting medical condition in Participant administered study drug and that may or may not have a causal relationship with drug treatment. All AEs will be graded using the NCI CTCAE v5.0 criteria. Serious Adverse Event (SAE); an untoward medical occurrence at any dose that: Results in death; Is life-threatening; Requires inpatient hospitalization or causes prolongation of existing hospitalization; Results in persistent or significant disability/incapacity; Is a congenital anomaly/birth defect; Is an important medical event that may not be immediately life- threatening or result in death or hospitalization but, may jeopardize the participant or may require intervention to prevent one of the other serious outcomes; or, potential drug induced liver injury (DILI).
From time of signing the informed consent document until death, or lost to follow-up (approximately 3 years)
Secondary Outcomes (3)
Observed Rate of Renal Elimination of 225Ac-MTI-201
3 to 24 hours post-dose
Observed Rate of Elimination from Blood of 225Ac-MTI-201
Prior to the initial dose on day 1; 0.042, 0.083, 0.167, 0.333, 0.667, 1.333, 2.333, 24, and 48 hours; day 8; and day 15 post-dose
Number of Participants Who Experienced a Complete Response (CR), Partial Response (PR), Progressive Disease (PD), or Stable Disease (SD) According to Tumor Lesion Measurement
From time of signing the informed consent document until death, or lost to follow-up (approximately 3 years)
Study Arms (12)
225Ac-MTI-201 4.7 microCi
EXPERIMENTALCohort 1: Participants were administered a single dose of 4.7 microCi of 225Ac-MTI-201 via intravenous catheter, with up to 3 years of follow-up.
225Ac-MTI-201 9.5 microCi
EXPERIMENTALCohort 2: Participants were administered a single dose of 9.5 microCi of 225Ac-MTI-201 via intravenous catheter, with up to 3 years of follow-up.
225Ac-MTI-201 19 microCi
EXPERIMENTALCohort 3: Participants were administered a single dose of 19 microCi of 225Ac-MTI-201 via intravenous catheter, with up to 3 years of follow-up.
225Ac-MTI-201 38 microCi
EXPERIMENTALCohort 4: Participants were administered a single dose of 38 microCi of 225Ac-MTI-201 via intravenous catheter, with up to 3 years of follow-up.
225Ac-MTI-201 76 microCi
EXPERIMENTALCohort 5: Participants were administered a single dose of 76 microCi of 225Ac-MTI-201 via intravenous catheter, with up to 3 years of follow-up.
225Ac-MTI-201 152 microCi
EXPERIMENTALCohort 6: Participants were administered a single dose of 152 microCi of 225Ac-MTI-201 via intravenous catheter, with up to 3 years of follow-up.
225Ac-MTI-201 254 microCi
EXPERIMENTALCohort 7: Participants were administered a single dose of 254 microCi of 225Ac-MTI-201 via intravenous catheter, with up to 3 years of follow-up.
225Ac-MTI-201 424 microCi
EXPERIMENTALCohort 8: Participants were administered a single dose of 424 microCi of 225Ac-MTI-201 via intravenous catheter, with up to 3 years of follow-up.
225Ac-MTI-201 564 microCi
EXPERIMENTALCohort 9: Participants were administered a single dose of 564 microCi of 225Ac-MTI-201 via intravenous catheter, with up to 3 years of follow-up.
225Ac-MTI-201 750 microCi
EXPERIMENTALCohort 10: Participants were administered a single dose of 750 microCi of 225Ac-MTI-201 via intravenous catheter, with up to 3 years of follow-up.
225Ac-MTI-201 998 microCi
EXPERIMENTALCohort 11: Participants were administered a single dose of 998 microCi of 225Ac-MTI-201 via intravenous catheter, with up to 3 years of follow-up.
225Ac-MTI-201 1327 microCi
EXPERIMENTALCohort 12: Participants were administered a single dose of 1327 microCi of 225Ac-MTI-201 via intravenous catheter, with up to 3 years of follow-up.
Interventions
4.7 microCi intravenous solution
9.5 microCi intravenous solution
19 microCi intravenous solution
38 microCi intravenous solution
76 microCi intravenous solution
152 microCi intravenous solution
254 microCi intravenous solution
424 microCi intravenous solution
564 microCi intravenous solution
750 microCi intravenous solution
998 microCi intravenous solution
1327 microCi intravenous solution
Eligibility Criteria
You may qualify if:
- Histologically confirmed metastatic uveal melanoma.
- Progression after at least one prior line of therapy for metastatic uveal melanoma. Liver directed therapy (e.g., hepatic arterial embolization, isolated hepatic perfusion) will count as one line of therapy. Should any additional treatment(s) receive regulatory approval for metastatic uveal melanoma during the conduct of this trial, participants (if eligible for the newly approved treatment) would need to demonstrate disease progression on the additional treatment(s) before being eligible to participate in the current study. There is no limit to the number of previous treatments for metastatic disease.
- Participants must have measurable disease per RECIST 1.1.
- Adults, age 18 or over, with no upper age limit.
- ECOG (Eastern Cooperative Oncology Group) performance status of 0-1 (Karnofsky ≥ 70 percent).
- Acceptable organ and marrow function as defined below:
- Leucocytes ≥ 3,000/μL
- Absolute neutrophil count ≥ 1,500/μL
- Platelets ≥ 100,000/μL
- Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT) ≤ 2.5x institutional upper limit of normal (ULN)
- Bilirubin ≤ 1.5x institutional upper limit of normal (ULN)
- Creatinine clearance ≥ 60mL/min/1.73m\^2 (measured by Cockcroft-Gault equation using actual body weight in kilograms, and then adjusted for body surface area)
- Male participants who are sexually active, and female participants of childbearing potential must agree to use 2 forms of FDA approved contraceptive methods during treatment with 225Ac-MTI-201 and up to 3 months following treatment.
- Ability to understand and the willingness to sign a written informed consent document.
You may not qualify if:
- Prior alpha-particle therapy.
- Has known symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are stable without evidence of progression by imaging for at least four weeks after definitive intervention and using no more than the equivalent of dexamethasone 2 mg/d for the management of vasogenic edema, if necessary. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
- Participants with an active malignancy requiring anticancer treatment at the time of study entry that, in the judgment of the investigator could impact the results of treatment of metastatic uveal melanoma.
- Pregnant or nursing women. Women of childbearing potential (defined as having had a menstrual cycle within the past 12 months, and not having had a surgical procedure for sterilization) must have a negative pregnancy test (urine or serum) within 7 days of treatment with 225Ac-MTI-201.
- Participants with uncontrolled inter-current illness including, but not limited to, ongoing or active bacterial infection, active hepatitis B/C infection requiring antiviral therapy, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Prior external beam radiation therapy to more than 25 percent of the bone marrow.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612, United States
Related Publications (3)
Tafreshi NK, Doligalski ML, Tichacek CJ, Pandya DN, Budzevich MM, El-Haddad G, Khushalani NI, Moros EG, McLaughlin ML, Wadas TJ, Morse DL. Development of Targeted Alpha Particle Therapy for Solid Tumors. Molecules. 2019 Nov 26;24(23):4314. doi: 10.3390/molecules24234314.
PMID: 31779154BACKGROUNDTafreshi NK, Tichacek CJ, Pandya DN, Doligalski ML, Budzevich MM, Kil H, Bhatt NB, Kock ND, Messina JL, Ruiz EE, Delva NC, Weaver A, Gibbons WR, Boulware DC, Khushalani NI, El-Haddad G, Triozzi PL, Moros EG, McLaughlin ML, Wadas TJ, Morse DL. Melanocortin 1 Receptor-Targeted alpha-Particle Therapy for Metastatic Uveal Melanoma. J Nucl Med. 2019 Aug;60(8):1124-1133. doi: 10.2967/jnumed.118.217240. Epub 2019 Feb 7.
PMID: 30733316BACKGROUNDTafreshi NK, Kil H, Pandya DN, Tichacek CJ, Doligalski ML, Budzevich MM, Delva NC, Langsen ML, Vallas JA, Boulware DC, Engelman RW, Gage KL, Moros EG, Wadas TJ, McLaughlin ML, Morse DL. Lipophilicity Determines Routes of Uptake and Clearance, and Toxicity of an Alpha-Particle-Emitting Peptide Receptor Radiotherapy. ACS Pharmacol Transl Sci. 2021 Mar 12;4(2):953-965. doi: 10.1021/acsptsci.1c00035. eCollection 2021 Apr 9.
PMID: 33860213BACKGROUND
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Mark L McLaughlin
Modulation Therapeutics, Inc.
- PRINCIPAL INVESTIGATOR
Nikhil I Khushalani, MD
H. Lee Moffitt Cancer Center and Research Institute
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 9, 2022
First Posted
August 11, 2022
Study Start
July 21, 2022
Primary Completion
March 31, 2026
Study Completion (Estimated)
February 25, 2029
Last Updated
October 30, 2025
Record last verified: 2025-10
Data Sharing
- IPD Sharing
- Will not share