ClinicalTrials.Veeva

Menu

Targeted Alpha Particle Radiotherapy for Metastatic Uveal Melanoma

M

Modulation Therapeutics

Status and phase

Enrolling
Phase 1

Conditions

Metastatic
Uveal Melanoma

Treatments

Drug: 1327 microCi of 225Ac-MTI-201
Drug: 564 microCi of 225Ac-MTI-201
Drug: 9.5 microCi of 225Ac-MTI-201
Drug: 750 microCi of 225Ac-MTI-201
Drug: 254 microCi of 225Ac-MTI-201
Drug: 152 microCi of 225Ac-MTI-201
Drug: 998 microCi of 225Ac-MTI-201
Drug: 424 microCi of 225Ac-MTI-201
Drug: 38 microCi of 225Ac-MTI-201
Drug: 4.7 microCi 225Ac-MTI-201
Drug: 19 microCi of 225Ac-MTI-201
Drug: 76 microCi of 225Ac-MTI-201

Study type

Interventional

Funder types

Other
Industry

Identifiers

NCT05496686
MTI201-IA (Other Identifier)
MCC 19868

Details and patient eligibility

About

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.

Full 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.

Enrollment

16 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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 (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.

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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

16 participants in 12 patient groups

225Ac-MTI-201 4.7 microCi
Experimental group
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.
Treatment:
Drug: 4.7 microCi 225Ac-MTI-201
225Ac-MTI-201 9.5 microCi
Experimental group
Description:
Cohort 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.
Treatment:
Drug: 9.5 microCi of 225Ac-MTI-201
225Ac-MTI-201 19 microCi
Experimental group
Description:
Cohort 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.
Treatment:
Drug: 19 microCi of 225Ac-MTI-201
225Ac-MTI-201 38 microCi
Experimental group
Description:
Cohort 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.
Treatment:
Drug: 38 microCi of 225Ac-MTI-201
225Ac-MTI-201 76 microCi
Experimental group
Description:
Cohort 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.
Treatment:
Drug: 76 microCi of 225Ac-MTI-201
225Ac-MTI-201 152 microCi
Experimental group
Description:
Cohort 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.
Treatment:
Drug: 152 microCi of 225Ac-MTI-201
225Ac-MTI-201 254 microCi
Experimental group
Description:
Cohort 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.
Treatment:
Drug: 254 microCi of 225Ac-MTI-201
225Ac-MTI-201 424 microCi
Experimental group
Description:
Cohort 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.
Treatment:
Drug: 424 microCi of 225Ac-MTI-201
225Ac-MTI-201 564 microCi
Experimental group
Description:
Cohort 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.
Treatment:
Drug: 564 microCi of 225Ac-MTI-201
225Ac-MTI-201 750 microCi
Experimental group
Description:
Cohort 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.
Treatment:
Drug: 750 microCi of 225Ac-MTI-201
225Ac-MTI-201 998 microCi
Experimental group
Description:
Cohort 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.
Treatment:
Drug: 998 microCi of 225Ac-MTI-201
225Ac-MTI-201 1327 microCi
Experimental group
Description:
Cohort 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.
Treatment:
Drug: 1327 microCi of 225Ac-MTI-201

Trial contacts and locations

1

Loading...

Central trial contact

Mark L McLaughlin, PhD; Karen E Hayes, PhD

Data sourced from clinicaltrials.gov

Clinical trials

Find clinical trialsTrials by location
© Copyright 2024 Veeva Systems