Trial Title:
Targeted Alpha Particle Radiotherapy for Metastatic Uveal Melanoma
NCT ID:
NCT05496686
Condition:
Uveal Melanoma
Metastatic
Conditions: Official terms:
Melanoma
Uveal Neoplasms
Conditions: Keywords:
Uveal Neoplasms
Melanoma of the Uvea
Melanocortin 1 Receptor
MC1R
Peptide Receptor Radiotherapeutic
PRRT
Actinium-225-PRRT
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
The continual reassessment method (CRM) will be used for this study. The dose escalation
plan is for a doubling of the dose for doses 2 through 6, a 1.67-fold increase for doses
7 and 8, and a 1.33-fold increase for doses 9-12. This plan corresponds roughly to the
modified Fibonacci dose escalation plan given by Penel and Kramar.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
4.7 microCi 225Ac-MTI-201
Description:
4.7 microCi intravenous solution
Arm group label:
225Ac-MTI-201 4.7 microCi
Other name:
4.7 microCi 225Actinium-MTI-201
Intervention type:
Drug
Intervention name:
9.5 microCi of 225Ac-MTI-201
Description:
9.5 microCi intravenous solution
Arm group label:
225Ac-MTI-201 9.5 microCi
Other name:
9.5 microCi 225Actinium-MTI-201
Intervention type:
Drug
Intervention name:
19 microCi of 225Ac-MTI-201
Description:
19 microCi intravenous solution
Arm group label:
225Ac-MTI-201 19 microCi
Other name:
19 microCi 225Actinium-MTI-201
Intervention type:
Drug
Intervention name:
38 microCi of 225Ac-MTI-201
Description:
38 microCi intravenous solution
Arm group label:
225Ac-MTI-201 38 microCi
Other name:
38 microCi 225Actinium-MTI-201
Intervention type:
Drug
Intervention name:
76 microCi of 225Ac-MTI-201
Description:
76 microCi intravenous solution
Arm group label:
225Ac-MTI-201 76 microCi
Other name:
76 microCi 225Actinium-MTI-201
Intervention type:
Drug
Intervention name:
152 microCi of 225Ac-MTI-201
Description:
152 microCi intravenous solution
Arm group label:
225Ac-MTI-201 152 microCi
Other name:
152 microCi 225Actinium-MTI-201
Intervention type:
Drug
Intervention name:
254 microCi of 225Ac-MTI-201
Description:
254 microCi intravenous solution
Arm group label:
225Ac-MTI-201 254 microCi
Other name:
254 microCi 225Actinium-MTI-201
Intervention type:
Drug
Intervention name:
424 microCi of 225Ac-MTI-201
Description:
424 microCi intravenous solution
Arm group label:
225Ac-MTI-201 424 microCi
Other name:
424 microCi 225Actinium-MTI-201
Intervention type:
Drug
Intervention name:
564 microCi of 225Ac-MTI-201
Description:
564 microCi intravenous solution
Arm group label:
225Ac-MTI-201 564 microCi
Other name:
564 microCi 225Actinium-MTI-201
Intervention type:
Drug
Intervention name:
750 microCi of 225Ac-MTI-201
Description:
750 microCi intravenous solution
Arm group label:
225Ac-MTI-201 750 microCi
Other name:
750 microCi 225Actinium-MTI-201
Intervention type:
Drug
Intervention name:
998 microCi of 225Ac-MTI-201
Description:
998 microCi intravenous solution
Arm group label:
225Ac-MTI-201 998 microCi
Other name:
998 microCi 225Actinium-MTI-201
Intervention type:
Drug
Intervention name:
1327 microCi of 225Ac-MTI-201
Description:
1327 microCi intravenous solution
Arm group label:
225Ac-MTI-201 1327 microCi
Other name:
1327 microCi 225Actinium-MTI-201
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.
Criteria for 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 (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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
H. Lee Moffitt Cancer Center and Research Institute
Address:
City:
Tampa
Zip:
33612
Country:
United States
Status:
Recruiting
Contact:
Last name:
Leticia Tetteh, RN, BScN
Phone:
813-745-4617
Email:
Leticia.Tetteh@moffitt.org
Investigator:
Last name:
Nikhil I Khushalani, MD
Email:
Principal Investigator
Investigator:
Last name:
Ghassan El-Haddad, MD
Email:
Sub-Investigator
Investigator:
Last name:
Eduardo G Moros, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Kenneth L Gage, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
David L Morse, PhD
Email:
Sub-Investigator
Start date:
July 21, 2022
Completion date:
February 25, 2029
Lead sponsor:
Agency:
Modulation Therapeutics, Inc.
Agency class:
Industry
Collaborator:
Agency:
H. Lee Moffitt Cancer Center and Research Institute
Agency class:
Other
Source:
Modulation Therapeutics, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05496686
