What side effects are associated with this type of intervention?

The most common treatments for uveal melanoma, particularly those involving targeted radiotherapy such as Actinium-225 (225Ac-MTI-201), can lead to a range of side effects. These may include ocular toxicity such as dry eyes, blurred vision, and eye pain. More severe ocular complications can include retinal toxicity, macular edema, and retinal vein occlusion. Systemic side effects may also occur, including fatigue, nausea, and potential damage to surrounding healthy tissues due to radiation exposure. It is crucial for patients to be closely monitored by their healthcare team to manage these side effects effectively.

What prior FDA approvals exist?

There is no specific mention of prior FDA approvals for treatments of uveal melanoma that are similar to the targeted radiotherapy using Actinium-225 (225Ac-MTI-201). Generally, treatments for metastatic uveal melanoma have included systemic therapies such as immunotherapy and targeted therapies, but the use of alpha particle radiotherapy like 225Ac-MTI-201 is still under investigation and has not been previously approved by the FDA.

What other types of research exist?

Promising alternatives to 225Ac-MTI-201 for Uveal Melanoma patients include immunotherapy agents such as nivolumab and ipilimumab, which have shown benefits in other cancers and are being explored for uveal melanoma. Additionally, targeted therapies like cabozantinib and pembrolizumab, which have demonstrated efficacy in other metastatic cancers, may also be considered.

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Radiopharmaceutical

Alpha Particle Radiotherapy for Eye Cancer

Phase 1

Recruiting

Led By Nikhil I Khushalani, MD

Research Sponsored by Modulation Therapeutics, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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)

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

Must not have

Prior alpha-particle therapy

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from time of signing the informed consent document until death, or lost to follow-up (approximately 3 years)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug in patients with a specific type of eye cancer that has spread and hasn't responded to other treatments. The drug uses a radioactive substance to kill cancer cells.

Who is the study for?

Adults with metastatic uveal melanoma who've had at least one prior treatment can join. They must have good performance status, measurable disease, and proper organ/marrow function. Participants need to use two forms of contraception if applicable and sign consent. Excluded are pregnant/nursing women, those with uncontrolled illnesses or certain other cancers, prior alpha-particle therapy recipients, and individuals with symptomatic brain metastases or significant immunocompromise.

What is being tested?

The trial is testing different doses of a radiotherapy drug called 225Ac-MTI-201 to find the highest dose patients can tolerate without severe side effects (MTD). It also looks at how the body processes the drug and its toxic effects in those with metastatic uveal melanoma.

What are the potential side effects?

Potential side effects include radiation-related risks such as damage to nearby tissues or organs, blood count changes that could lead to anemia or infection risk increase, fatigue from radiation exposure, nausea or vomiting. Specific side effect profiles will be monitored closely.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My blood tests show normal organ function.

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My uveal melanoma has worsened after at least one treatment.

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I am fully active or can carry out light work.

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My cancer is a type of melanoma that started in the eye and has spread.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have previously received alpha-particle therapy.

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I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

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I have had radiation therapy to over 25% of my bone marrow.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from time of signing the informed consent document until death, or lost to follow-up (approximately 3 years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from time of signing the informed consent document until death, or lost to follow-up (approximately 3 years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and from time of signing the informed consent document until death, or lost to follow-up (approximately 3 years) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

The Number of Participants Who Experienced Serious or Non-Serious Adverse Events

Secondary study objectives

Number of Participants Who Experienced a Complete Response (CR), Partial Response (PR), Progressive Disease (PD), or Stable Disease (SD) According to Tumor Lesion Measurement

Observed Rate of Elimination from Blood of 225Ac-MTI-201

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

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

12Treatment groups

Experimental Treatment

Group I: 225Ac-MTI-201 998 microCiExperimental Treatment1 Intervention

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.

Group II: 225Ac-MTI-201 9.5 microCiExperimental Treatment1 Intervention

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.

Group III: 225Ac-MTI-201 76 microCiExperimental Treatment1 Intervention

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.

Group IV: 225Ac-MTI-201 750 microCiExperimental Treatment1 Intervention

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.

Group V: 225Ac-MTI-201 564 microCiExperimental Treatment1 Intervention

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.

Group VI: 225Ac-MTI-201 424 microCiExperimental Treatment1 Intervention

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.

Group VII: 225Ac-MTI-201 4.7 microCiExperimental Treatment1 Intervention

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.

Group VIII: 225Ac-MTI-201 38 microCiExperimental Treatment1 Intervention

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.

Group IX: 225Ac-MTI-201 254 microCiExperimental Treatment1 Intervention

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.

Group X: 225Ac-MTI-201 19 microCiExperimental Treatment1 Intervention

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.

Group XI: 225Ac-MTI-201 152 microCiExperimental Treatment1 Intervention

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.

Group XII: 225Ac-MTI-201 1327 microCiExperimental Treatment1 Intervention

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.

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Targeted alpha particle radiotherapy, such as the use of Actinium-225 (225Ac-MTI-201), works by delivering highly potent alpha radiation directly to cancer cells, causing double-strand DNA breaks that lead to cell death. This method is highly specific, minimizing damage to surrounding healthy tissues. Other common treatments for Uveal Melanoma include plaque brachytherapy, which involves placing a radioactive plaque near the tumor to deliver localized radiation, and proton therapy, which uses protons to precisely target the tumor while sparing adjacent normal tissues. These treatments are crucial for Uveal Melanoma patients as they offer targeted approaches that maximize tumor control while reducing collateral damage, thereby preserving vision and improving quality of life.