Active, not recruiting
Phase 1
Targeted Alpha Particle Radiotherapy for Metastatic Uveal Melanoma
Condition(s) studied
Uveal MelanomaMetastatic
Investigational drug(s) / intervention(s)
4.7 microCi 225Ac-MTI-2019.5 microCi of 225Ac-MTI-20119 microCi of 225Ac-MTI-20138 microCi of 225Ac-MTI-20176 microCi of 225Ac-MTI-201152 microCi of 225Ac-MTI-201254 microCi of 225Ac-MTI-201424 microCi of 225Ac-MTI-201564 microCi of 225Ac-MTI-201750 microCi of 225Ac-MTI-201998 microCi of 225Ac-MTI-2011327 microCi of 225Ac-MTI-201
4.7 microCi 225Ac-MTI-201: 4.7 microCi intravenous solution
9.5 microCi of 225Ac-MTI-201: 9.5 microCi intravenous solution
19 microCi of 225Ac-MTI-201: 19 microCi intravenous solution
38 microCi of 225Ac-MTI-201: 38 microCi intravenous solution
76 microCi of 225Ac-MTI-201: 76 microCi intravenous solution
152 microCi of 225Ac-MTI-201: 152 microCi intravenous solution
254 microCi of 225Ac-MTI-201: 254 microCi intravenous solution
424 microCi of 225Ac-MTI-201: 424 microCi intravenous solution
564 microCi of 225Ac-MTI-201: 564 microCi intravenous solution
750 microCi of 225Ac-MTI-201: 750 microCi intravenous solution
998 microCi of 225Ac-MTI-201: 998 microCi intravenous solution
1327 microCi of 225Ac-MTI-201: 1327 microCi intravenous solution
Study 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.
Eligibility
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.
Primary outcome measure(s)
- Maximum Tolerated Dose (MTD) of 225Ac-MTI-201 — Within 4 weeks after study drug administration
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.
- Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) — Within 4 weeks after study drug administration
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
- The Number of Participants Who Experienced Serious or Non-Serious Adverse Events — From time of signing the informed consent document until death, or lost to follow-up (approximately 3 years)
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).
Trial sites (1)
| Facility | City | Region | Status |
|---|
| H. Lee Moffitt Cancer Center and Research Institute |
Tampa |
Florida |
|
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