Actium-225-Prostate Specific Membrane Antigen Imaging & Therapy

Trial Title: Actium-225-Prostate Specific Membrane Antigen Imaging & Therapy

NCT ID: NCT05902247

Condition: Prostatic Neoplasms, Castration-Resistant

Conditions: Official terms:
Prostatic Neoplasms
Prostatic Neoplasms, Castration-Resistant

Conditions: Keywords:
225Ac-PSMA
Prostate cancer

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Intervention model description: A clinical prospective, single-center, single-arm, phase I dose escalation therapy study.

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Radiation
Intervention name: Radionuclide Therapy
Description: To evaluate the tolerability and safety of 225Ac-PSMA I&T in patients with metastatic prostate cancer
Arm group label: 225Ac-PSMA I&T

Other name: 225Ac-PSMA I&T

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.

Detailed 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

Criteria for eligibility:
Criteria:
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

Gender: Male

Gender based: Yes

Gender description: Male

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Erasmus Medical Center

Address:
City: Rotterdam
Zip: 3015GD
Country: Netherlands

Status: Recruiting

Contact:
Last name: Sui wai Ling Ling

Phone: +31107033612
Email: s.ling@erasmusmc.nl

Contact backup:
Last name: Laurens Groenendijk

Phone: +31107033612
Email: imaging.trialbureau@erasmusmc.nl

Start date: December 29, 2021

Completion date: December 29, 2025

Lead sponsor:
Agency: Erasmus Medical Center
Agency class: Other

Collaborator:
Agency: Dutch Cancer Society
Agency class: Other

Source: Erasmus Medical Center

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05902247