Actium-225-Prostate Specific Membrane Antigen Imaging & Therapy

Prostatic Neoplasms, Castration-Resistant Clinical Trial

— 225AcPSMAI&T  

Official title:

Phase I Dose Escalation Study to Evaluate Tolerability and Safety of 225Ac-PSMA I&T in Patients With Metastatic Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05902247
• Other study ID #: NL73234.078.20
• Status: Recruiting
• Phase: Phase 1
• Start date: December 29, 2021
• Est. completion date: December 29, 2025

Study information

• Verified date: June 2023
• Source: Erasmus Medical Center
• Contact: Sui wai Ling
• Phone: +31107033612
• Email: s.ling[@]erasmusmc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

225Ac-PSMA I&T is a radiopharmaceutical for therapy of prostate cancer. PSMA is overexpressed on prostate cancer cells. Actium-225 is an alpha emitting radionuclide. When PSMA I&T is labelled with Actium-225, it can be applied as therapy for prostate cancer.

Description:

Rationale:

225Ac-PSMA I&T is a radiopharmaceutical for therapy of prostate cancer. PSMA is overexpressed on prostate cancer cells. Actium-225 is an alpha emitting radionuclide. When PSMA I&T is labelled with Actium-225, it can be applied as therapy for prostate cancer.

Objective:

To evaluate the tolerability and safety of 225Ac-PSMA I&T in patients with metastatic prostate cancer and recommend a dose for further phase 2 studies.

Study design:

A clinical prospective, single-center, single-arm, phase I dose escalation therapy study.

Study population:

Up to 30 patients with advanced metastatic castration-resistant prostate cancer (mCRPC).

Intervention:

Patients with advanced mCRPC will receive therapy with 225Ac-PSMA I&T. The first dose-level will not exceed 8 megabecquerel (MBq), as this is reported in the literature as a save activity for treatment. A Positron Emission Tomography - Magnetic Resonance Imaging (PET-MRI) with Gallium-68-PSMA I&T (68Ga) will be performed to calculate the precise dose-level needed and as a verification the precise dose-level will be compared with the dose-level of 8 MBq. In the first week after therapy, the PET-MRI will be repeated to observe any effects of the alpha radiation on the metastases and observe the potential changes in 68Ga-PSMA I&T uptake. Eight weeks after the first cycle, patients will receive the second cycle of 225Ac-PSMA I&T. If no Dose Limiting Toxicity (DLT) occurs, the dose can be increased for the next DL. If a DLT occurs, the cohort will be expanded to 6 patients. After establishing the recommended dose, an expansion cohort will be opened with a total of 12 patients.

Main study endpoints:

To investigate the safety, tolerability and biochemical effects of 225Ac-PSMA I&T injected in patients with metastatic prostate cancer.

Primary objective:

• To assess the safety and tolerability of 225Ac-PSMA I&T administered intravenously

Secondary objectives:

• To predict and calculate the absorbed-dose in critical organs (e.g. salivary glands, kidneys, bone marrow) by 68Ga-PSMA I&T PET-MRI

• To evaluate the effects of the radionuclide therapy on metastases in the days after therapy using 68Ga-PSMA I&T PET-MRI

• To evaluate the biochemical effects of 225Ac-PSMA I&T therapy in patients with metastatic prostate cancer

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 29, 2025
• Est. primary completion date: December 29, 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histopathological proven metastatic castration resistant prostate cancer. Castrationresistant disease is defined as a serum testosterone level of 50 nanogram per deciliter or lower (=1.7 nanomol per liter) after bilateral orchiectomy or during maintenance treatment consisting of androgen-ablation therapy with a luteinizing hormone-releasing hormone agonist.

• Evidence of progressive disease, defined as 1 or more Prostate Cancer Work Grouping 3 (PCWG3) criteria: - PSA level = 1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart

• Progression as defined by RECIST 1.1 with PCGW3 modifications

• Progression after at least one line of chemotherapy and/or one line of nonsteroidal antiandrogen (NSAA).

• No active anti-tumor therapy, except for androgen deprivation therapy in combination with at least one androgen receptor-targeted agent

• Willing and able to undergo 2 cycles of 225Ac-PSMA I&T therapy and 3 PET-MRI scans in 16 weeks and comply with protocol

• Signed and dated written informed consent by the patient (or legal representative) prior to any study-specific procedures.

• Age = 18 years.

• Eastern Cooperative Oncology Group (ECOG) performance-status score 0-2.

• Use of highly effective methods of contraception (female partners of male participants)

• During the trial and 6 months after completion of the study or willing to practice sexual abstinence.

Exclusion Criteria:

• Concurrent severe illness or clinically relevant trauma within 2 weeks before the administration of the investigational product that might preclude study completion or interfere with study results

• Serum hemoglobin = 6.2 mmol/L, total white blood cell (WBC) count = 3.5·109/L, absolute neutrophil count = 1.5·109/L, platelet count = 100·109/L, serum creatinine concentration = 150 umol/L (= 1.7 mg/dL), serum albumin <30 g/L, bilirubin = 1.5 x upper limit normal (ULN), aspartate transaminase (ASAT) = 3 x ULN and alanine aminotransferase (ALAT) = 3 x ULN (or bilirubin = 3 x ULN, ASAT = 5 x ULN and ALAT = 5 x ULN in the case of pre-existing liver metastases at baseline)

• Concurrent bladder outflow obstruction or unmanageable urinary incontinence

• Known or expected hypersensitivity to Gallium-68, Actinium-225, PSMA I&T, or any excipient present in 225Ac/68Ga-PSMA I&T

• Prior administration of a radiopharmaceutical within a period corresponding to 8 halflives of the radionuclide used on such radiopharmaceutical

• Prior treatment with any radionuclide therapy

• History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study

• Central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord compression

• Radiation therapy within 4 weeks of first dose (or local or focal radiotherapy within 2 weeks of first dose)

• Male subjects unwilling to abstain from donating sperm during treatment and for an additional 6 months after the last dose

Related Conditions & MeSH terms

• Prostatic Neoplasms
• Prostatic Neoplasms, Castration-Resistant

Intervention

Radiation:
• Radionuclide Therapy
To evaluate the tolerability and safety of 225Ac-PSMA I&T in patients with metastatic prostate cancer

Locations

Country	Name	City	State
Netherlands	Erasmus Medical Center	Rotterdam	Zuid-Holland

Sponsors (2)

Lead Sponsor	Collaborator
Erasmus Medical Center	Dutch Cancer Society

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of Adverse Events and Serious Adverse Events as assessed by CTCAE v5.0	Safety and tolerability assessment	4 years
Primary	Absolute values and changes from baseline in laboratory parameters (hematology, blood chemistry and urinalysis), including assessment of shifts from baseline to abnormal values on treatment	Safety and tolerability assessment	4 years
Primary	Absolute values and changes from baseline in vital signs & ECG parameters	Safety and tolerability assessment	4 years
Secondary	To predict and calculate the absorbed-dose in critical organs (e.g. salivary glands, kidneys, bone marrow) by 68Ga-PSMA I&T PET-MRI	Dosimetry	4 years
Secondary	Changes in SUVmax of the target lesions on PET-MRI and morphological changes evaluated on MRI	Direct effect of 225Ac-PSMA I&T	4 years
Secondary	Objective response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria v.1.1.	Preliminary efficacy	4 years
Secondary	Percent changes from baseline in tumor size where tumor size is defined as the sum of all target lesions as measured by RECIST criteria v.1.1.	Preliminary efficacy	4 years
Secondary	Prostate Specific Antigen(PSA) response rate assessed from treatment visit 1 defined as a decrease in PSA of = 50% from baseline.	Preliminary efficacy	4 years
Secondary	Percent change from baseline in PSA as a continuous endpoint by visit and maximum reduction during the study	Preliminary efficacy	4 years
Secondary	Percent change from baseline values of pain questionnaire at every treatment visit	Preliminary efficacy	4 years
Secondary	Overall Survival (OS) defined as the time from the date of first dose of 225Ac-PSMA I&T treatment to the date of death due to any cause.	Preliminary efficacy	4 years