Targeted Alpha Particle Radiotherapy for Metastatic Uveal Melanoma

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Brief Title

Targeted Alpha Particle Radiotherapy for Metastatic Uveal Melanoma

Official Title

First in Human Phase I Study of 225Actinium-MTI-201 (225Ac-MTI-201) in Metastatic Uveal Melanoma

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.
    

Detailed Description

      This study will enroll patients with metastatic uveal melanoma that have failed at least one
      form of therapy from a single academic medical center in the United States. All participants
      will be informed about the study and potential risks and required to provide written informed
      consent prior to undergoing study-related procedures. A continual reassessment method (CRM)
      design will be used for this clinical trial. The study proposes single patient cohorts with
      dose escalation starting at 4.7 microCi of 225Ac-MTI-201 after each cohort in the absence of
      safety concerns (2-fold increases for doses and lower dose increases between higher doses).
      Dose Limiting Toxicities will be assessed using the CTCAE version 5.0 criteria.

      The participants who meet the eligibility requirements will be administered a single
      intravenous dose of 225Ac-MTI-201. After study treatment, the study participants will stay
      overnight at the study center, undergo study procedures (i.e. vital signs, physical exam,
      multiple blood and urine sample collections) and will be scheduled to return to the clinic at
      48 hours and for additional appointments weekly clinic visits the first month and on Week 9
      for health status assessments, including physical exams, complete blood chemistry, and EKG.
      Tumor measurements every 8 weeks in first year post-injection; extended to 12 weeks in year
      2; every 16 weeks in year 3, and 24 weeks in years 4 and 5. The clinic visits will involve
      seeing a study doctor plus radiological tests (such as MRI and/or CT scans) to see how the
      metastatic uveal melanoma has responded to the study drug. The protocol and informed consent
      documents have been reviewed and approved by the hospital human subjects review board and the
      study will be performed in accordance with the Declaration of Helsinki.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Maximum Tolerated Dose (MTD) of 225Ac-MTI-201

Secondary Outcome

 Observed Rate of Renal Elimination of 225Ac-MTI-201

Condition

Uveal Melanoma

Intervention

4.7 microCi 225Ac-MTI-201

Study Arms / Comparison Groups

 225Ac-MTI-201 4.7 microCi
Description:  Cohort 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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

16

Start Date

July 21, 2022

Completion Date

February 25, 2029

Primary Completion Date

December 25, 2023

Eligibility Criteria

        Inclusion Criteria:

          -  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 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.

        Exclusion Criteria:

          -  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.

          -  Immunocompromised participants may be at increased risk of toxicity. Therefore,
             HIV-positive participants, participants with acquired or congenital immunodeficiency
             conditions, those on chronic systemic corticosteroids requiring >10 mg of prednisone
             or equivalent per day will be excluded from participation. (Participants with
             autoimmune disease who do not require corticosteroids or are maintained on ≤10 mg of
             prednisone or equivalent per day ARE eligible for participation; for participants with
             CNS metastases on steroids, exclusion criterion bullet point #2 above will apply).

          -  Prior external beam radiation therapy to more than 25 percent of the bone marrow.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Mark L McLaughlin, 813-786-0033, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT05496686

Organization ID

MCC 19868

Secondary IDs

MTI201-IA

Responsible Party

Sponsor

Study Sponsor

Modulation Therapeutics, Inc.

Collaborators

 H. Lee Moffitt Cancer Center and Research Institute

Study Sponsor

Mark L McLaughlin, Study Director, Modulation Therapeutics, Inc.


Verification Date

August 2022