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Actium-225-Prostate Specific Membrane Antigen Imaging & Therapy (225AcPSMAI&T)

Primary Purpose

Prostatic Neoplasms, Castration-Resistant

Status
Recruiting
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
Radionuclide Therapy
Sponsored by
Erasmus Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostatic Neoplasms, Castration-Resistant focused on measuring 225Ac-PSMA, Prostate cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • Erasmus Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

225Ac-PSMA I&T

Arm Description

225Ac-PSMA I&T

Outcomes

Primary Outcome Measures

Incidence and severity of Adverse Events and Serious Adverse Events as assessed by CTCAE v5.0
Safety and tolerability assessment
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
Absolute values and changes from baseline in vital signs & ECG parameters
Safety and tolerability assessment

Secondary Outcome Measures

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
Changes in SUVmax of the target lesions on PET-MRI and morphological changes evaluated on MRI
Direct effect of 225Ac-PSMA I&T
Objective response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria v.1.1.
Preliminary efficacy
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
Prostate Specific Antigen(PSA) response rate assessed from treatment visit 1 defined as a decrease in PSA of ≥ 50% from baseline.
Preliminary efficacy
Percent change from baseline in PSA as a continuous endpoint by visit and maximum reduction during the study
Preliminary efficacy
Percent change from baseline values of pain questionnaire at every treatment visit
Preliminary efficacy
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

Full Information

First Posted
May 24, 2023
Last Updated
June 5, 2023
Sponsor
Erasmus Medical Center
Collaborators
Dutch Cancer Society
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1. Study Identification

Unique Protocol Identification Number
NCT05902247
Brief Title
Actium-225-Prostate Specific Membrane Antigen Imaging & Therapy
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 29, 2021 (Actual)
Primary Completion Date
December 29, 2025 (Anticipated)
Study Completion Date
December 29, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Erasmus Medical Center
Collaborators
Dutch Cancer Society

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostatic Neoplasms, Castration-Resistant
Keywords
225Ac-PSMA, Prostate cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
A clinical prospective, single-center, single-arm, phase I dose escalation therapy study.
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
225Ac-PSMA I&T
Arm Type
Experimental
Arm Description
225Ac-PSMA I&T
Intervention Type
Radiation
Intervention Name(s)
Radionuclide Therapy
Other Intervention Name(s)
225Ac-PSMA I&T
Intervention Description
To evaluate the tolerability and safety of 225Ac-PSMA I&T in patients with metastatic prostate cancer
Primary Outcome Measure Information:
Title
Incidence and severity of Adverse Events and Serious Adverse Events as assessed by CTCAE v5.0
Description
Safety and tolerability assessment
Time Frame
4 years
Title
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
Description
Safety and tolerability assessment
Time Frame
4 years
Title
Absolute values and changes from baseline in vital signs & ECG parameters
Description
Safety and tolerability assessment
Time Frame
4 years
Secondary Outcome Measure Information:
Title
To predict and calculate the absorbed-dose in critical organs (e.g. salivary glands, kidneys, bone marrow) by 68Ga-PSMA I&T PET-MRI
Description
Dosimetry
Time Frame
4 years
Title
Changes in SUVmax of the target lesions on PET-MRI and morphological changes evaluated on MRI
Description
Direct effect of 225Ac-PSMA I&T
Time Frame
4 years
Title
Objective response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria v.1.1.
Description
Preliminary efficacy
Time Frame
4 years
Title
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.
Description
Preliminary efficacy
Time Frame
4 years
Title
Prostate Specific Antigen(PSA) response rate assessed from treatment visit 1 defined as a decrease in PSA of ≥ 50% from baseline.
Description
Preliminary efficacy
Time Frame
4 years
Title
Percent change from baseline in PSA as a continuous endpoint by visit and maximum reduction during the study
Description
Preliminary efficacy
Time Frame
4 years
Title
Percent change from baseline values of pain questionnaire at every treatment visit
Description
Preliminary efficacy
Time Frame
4 years
Title
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.
Description
Preliminary efficacy
Time Frame
4 years

10. Eligibility

Sex
Male
Gender Based
Yes
Gender Eligibility Description
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sui wai Ling
Phone
+31107033612
Email
s.ling@erasmusmc.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Laurens Groenendijk
Phone
+31107033612
Email
imaging.trialbureau@erasmusmc.nl
Facility Information:
Facility Name
Erasmus Medical Center
City
Rotterdam
State/Province
Zuid-Holland
ZIP/Postal Code
3015GD
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sui wai Ling Ling
Phone
+31107033612
Email
s.ling@erasmusmc.nl
First Name & Middle Initial & Last Name & Degree
Laurens Groenendijk
Phone
+31107033612
Email
imaging.trialbureau@erasmusmc.nl

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Actium-225-Prostate Specific Membrane Antigen Imaging & Therapy

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