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| ID | Type | Description | Link |
|---|---|---|---|
| 7R01CA207645-03 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Prostate Cancer Foundation | OTHER |
| United States Department of Defense | FED |
| National Institutes of Health (NIH) | NIH |
| National Cancer Institute (NCI) |
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This is an open-label, single-center Phase I dose escalation study designed to determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of 225Ac-J591 in a single dose regimen.
This clinical trial is for men with advanced prostate cancer. The purpose of this study is to find the highest dose level of the study drug, 225Ac-J591 that can be given without severe side effects. The research study is being done because the standard treatments for prostate cancer that has spread beyond the prostate gland are intended to minimize the adverse effects of the disease. These treatments, however, are not curative. Patients who choose to participate in this study will have a screening visit to determine whether or not they are eligible to participate in the study. The treatment phase is comprised of 8 visits over approximately 12 weeks. The study medication is called 225Ac-J591, and participants will receive an infusion of the study drug on the Treatment visit of the study. Upon completion of investigational treatment with single dose of 225Ac-J591, subjects will undergo 68Ga-PSMA-HBED-CC injection and same day PET/CT at the end of study visit to document treatment response. Subsequently survival data and additional treatment(s) information will be captured from their routine Standard of care (SOC) visits.During the other study visits, participants will undergo routine tests and procedures, such as physical examinations, and routine blood tests. Some blood tests will be done for research purposes only. After completion of therapy, participants may be contacted on a periodic basis to see how they are doing.
Key eligibility:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| All Subjects | Experimental | A single dose of 225Ac-J591 will be given to subjects with documented progressive metastatic CRPC. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 225Ac-J591 | Drug | 225Ac-J591 (13.3 KBq/Kg - 93.3 KBq/Kg or 0.36 uCi/Kg - 2.52 uCi/Kg) on day 1 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects With Dose Limiting Toxicities (DLT) | Count of participants will be measured by the recommended phase II dose in utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for DLTs. | Assessed from start of treatment to up to 8 weeks after first study drug administration. |
| Number of Subjects Who Reached Maximum Tolerated Dose (MTD) | The MTD is the highest dose amongst the different dose-level cohorts in this study at which no more than 2 (33%) of the subjects in a cohort experience DLT. | Assessed from start of treatment to up to 8 weeks after first study drug administration. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects With Prostate Specific Antigen (PSA) Response | PSA will be analyzed through blood specimen collection | PSA was assessed at screening, and up to 6 months after first treatment with study drug. |
| Number of Subjects With Circulating Tumor Cells (CTC) Response |
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Inclusion Criteria:
Histologically or cytologically confirmed adenocarcinoma of prostate
Documented progressive metastatic CRPC based on Prostate Cancer Working Group 3 (PCWG3) criteria, which includes at least one of the following criteria:
ECOG performance status of 0-2
Have serum testosterone < 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH analogue (agonist/antagonist) if they have not undergone bilateral orchiectomy.
Have previously been treated with at least one of the following:
Have previously received taxane chemotherapy, been determined to be ineligible for taxane chemotherapy by their physician, or refused taxane chemotherapy.
Age > 18 years
Patients must have normal organ and marrow function as defined below:
Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
Adult male patients of >18 years age with documented progressive metastatic CRPC
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| Name | Affiliation | Role |
|---|---|---|
| Scott Tagawa, MD | Weill Medical College of Cornell University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tulane Cancer Center Clinic | New Orleans | Louisiana | 70112 | United States | ||
| Weill Cornell Medical College |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37922438 | Derived | Tagawa ST, Thomas C, Sartor AO, Sun M, Stangl-Kremser J, Bissassar M, Vallabhajosula S, Huicochea Castellanos S, Nauseef JT, Sternberg CN, Molina A, Ballman K, Nanus DM, Osborne JR, Bander NH. Prostate-Specific Membrane Antigen-Targeting Alpha Emitter via Antibody Delivery for Metastatic Castration-Resistant Prostate Cancer: A Phase I Dose-Escalation Study of 225Ac-J591. J Clin Oncol. 2024 Mar 1;42(7):842-851. doi: 10.1200/JCO.23.00573. Epub 2023 Nov 3. | |
| 33465252 |
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Recruitment took place at at Weill Cornell Medicine New York Presbyterian and Tulane Medical Center.
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| ID | Title | Description |
|---|---|---|
| FG000 | 225Ac-J591 Cohort 1 | Cohort 1: Participants were administered of 225Ac-J591 once at the dose level of 13.3 KBq/Kg - 0.36 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment |
| FG001 | 225Ac-J591 Cohort 2 | Cohort 2: Participants were administered of 225Ac-J591 once at the dose level of 26.7 KBq/Kg - 0.72 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. |
| FG002 | 225Ac-J591 Cohort 3 | Cohort 3: Participants were administered of 225Ac-J591 once at the dose level of 40.0 KBq/Kg - 1.08 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. |
| FG003 | 225Ac-J591 Cohort 4 | Cohort 4: Participants were administered of 225Ac-J591 once at the dose level of 53.3 KBq/Kg - 1.44 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. |
| FG004 | 225Ac-J591 Cohort 5 | Cohort 5: Participants were administered of 225Ac-J591 once at the dose level of 66.7 KBq/Kg - 1.80 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. |
| FG005 | 225Ac-J591 Cohort 6 | Cohort 6: Participants were administered of 225Ac-J591 once at the dose level of 80.0 KBq/Kg - 2.16 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. |
| FG006 | 225Ac-J591 Cohort 7 | Cohort 7: Participants were administered of 225Ac-J591 once at the dose level of 93.3 KBq/Kg - 2.52 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 225Ac-J591 Cohort 1 | Cohort 1: Participants were administered of 225Ac-J591 once at the dose level of 13.3 KBq/Kg - 0.36 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment |
| BG001 | 225Ac-J591 Cohort 2 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Subjects With Dose Limiting Toxicities (DLT) | Count of participants will be measured by the recommended phase II dose in utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for DLTs. | Posted | Count of Participants | Participants | Assessed from start of treatment to up to 8 weeks after first study drug administration. |
|
Assessed throughout duration of participant on study, up to 3 years.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 225Ac-J591 Cohort 1 | Cohort 1: Participants were administered of 225Ac-J591 once at the dose level of 13.3 KBq/Kg - 0.36 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | CTCAE 4.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | CTCAE 4.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Scott Tagawa | Weill Cornell Medicine | 646-962-2027 | stt2007@med.cornell.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 30, 2021 | Sep 22, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C000718244 | gallium 68 PSMA-11 |
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| NIH |
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CTCs will be analyzed through blood specimen collection via CellSearch methodology lab testing |
| CTC was assessed at screening and 12 weeks after starting study drug. |
| Number of Subjects With Radiographic (Imaging) Response | Radiographic response rate by Response evaluation criteria in solid tumors (RECIST) criteria with Prostate Cancer Working Group 3 (PCWG3) modifications | Response were assessed for patients throughout their duration on the study, up to 3 years. |
| Progression Free Survival (PFS) | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | From the start of treatment to progression, up to 3 years |
| New York |
| New York |
| 10065 |
| United States |
| Vlachostergios PJ, Niaz MJ, Skafida M, Mosallaie SA, Thomas C, Christos PJ, Osborne JR, Molina AM, Nanus DM, Bander NH, Tagawa ST. Imaging expression of prostate-specific membrane antigen and response to PSMA-targeted beta-emitting radionuclide therapies in metastatic castration-resistant prostate cancer. Prostate. 2021 Apr;81(5):279-285. doi: 10.1002/pros.24104. Epub 2021 Jan 19. |
| Lost to Follow-up |
|
Cohort 2: Participants were administered of 225Ac-J591 once at the dose level of 26.7 KBq/Kg - 0.72 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. |
| BG002 | 225Ac-J591 Cohort 3 | Cohort 3: Participants were administered of 225Ac-J591 once at the dose level of 40.0 KBq/Kg - 1.08 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. |
| BG003 | 225Ac-J591 Cohort 4 | Cohort 4: Participants were administered of 225Ac-J591 once at the dose level of 53.3 KBq/Kg - 1.44 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. |
| BG004 | 225Ac-J591 Cohort 5 | Cohort 5: Participants were administered of 225Ac-J591 once at the dose level of 66.7 KBq/Kg - 1.80 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. |
| BG005 | 225Ac-J591 Cohort 6 | Cohort 6: Participants were administered of 225Ac-J591 once at the dose level of 80.0 KBq/Kg - 2.16 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. |
| BG006 | 225Ac-J591 Cohort 7 | Cohort 7 with Expansion: Participants were administered of 225Ac-J591 once at the dose level of 93.3 KBq/Kg - 2.52 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment |
| BG007 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG002 | 225Ac-J591 Cohort 3 | Cohort 3: Participants were administered of 225Ac-J591 once at the dose level of 40.0 KBq/Kg - 1.08 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. |
| OG003 | 225Ac-J591 Cohort 4 | Cohort 4: Participants were administered of 225Ac-J591 once at the dose level of 53.3 KBq/Kg - 1.44 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. |
| OG004 | 225Ac-J591 Cohort 5 | Cohort 5: Participants were administered of 225Ac-J591 once at the dose level of 66.7 KBq/Kg - 1.80 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. |
| OG005 | 225Ac-J591 Cohort 6 | Cohort 6: Participants were administered of 225Ac-J591 once at the dose level of 80.0 KBq/Kg - 2.16 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. |
| OG006 | 225Ac-J591 Cohort 7 | Cohort 7: Participants were administered of 225Ac-J591 once at the dose level of 93.3 KBq/Kg - 2.52 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. |
|
|
| Primary | Number of Subjects Who Reached Maximum Tolerated Dose (MTD) | The MTD is the highest dose amongst the different dose-level cohorts in this study at which no more than 2 (33%) of the subjects in a cohort experience DLT. | Posted | Count of Participants | Participants | Assessed from start of treatment to up to 8 weeks after first study drug administration. |
|
|
|
| Secondary | Number of Subjects With Prostate Specific Antigen (PSA) Response | PSA will be analyzed through blood specimen collection | Posted | Count of Participants | Participants | PSA was assessed at screening, and up to 6 months after first treatment with study drug. |
|
|
|
| Secondary | Number of Subjects With Circulating Tumor Cells (CTC) Response | CTCs will be analyzed through blood specimen collection via CellSearch methodology lab testing | Posted | Count of Participants | Participants | CTC was assessed at screening and 12 weeks after starting study drug. |
|
|
|
| Secondary | Number of Subjects With Radiographic (Imaging) Response | Radiographic response rate by Response evaluation criteria in solid tumors (RECIST) criteria with Prostate Cancer Working Group 3 (PCWG3) modifications | Posted | Count of Participants | Participants | Response were assessed for patients throughout their duration on the study, up to 3 years. |
|
|
|
| Secondary | Progression Free Survival (PFS) | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | Posted | Median | Full Range | Days | From the start of treatment to progression, up to 3 years |
|
|
|
| 1 |
| 1 |
| 0 |
| 1 |
| 1 |
| 1 |
| EG001 | 225Ac-J591 Cohort 2 | Cohort 2: Participants were administered of 225Ac-J591 once at the dose level of 26.7 KBq/Kg - 0.72 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. | 1 | 1 | 0 | 1 | 1 | 1 |
| EG002 | 225Ac-J591 Cohort 3 | Cohort 3: Participants were administered of 225Ac-J591 once at the dose level of 40.0 KBq/Kg - 1.08 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. | 1 | 1 | 0 | 1 | 1 | 1 |
| EG003 | 225Ac-J591 Cohort 4 | Cohort 4: Participants were administered of 225Ac-J591 once at the dose level of 53.3 KBq/Kg - 1.44 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. | 1 | 1 | 0 | 1 | 1 | 1 |
| EG004 | 225Ac-J591 Cohort 5 | Cohort 5: Participants were administered of 225Ac-J591 once at the dose level of 66.7 KBq/Kg - 1.80 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. | 6 | 6 | 3 | 6 | 6 | 6 |
| EG005 | 225Ac-J591 Cohort 6 | Cohort 6: Participants were administered of 225Ac-J591 once at the dose level of 80.0 KBq/Kg - 2.16 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. | 6 | 6 | 2 | 6 | 6 | 6 |
| EG006 | 225Ac-J591 Cohort 7 | Cohort 7 with Expansion: Participants were administered of 225Ac-J591 once at the dose level of 93.3 KBq/Kg - 2.52 Ci/Kg via intravenous infusion (IV). Participants were then followed until death for survival assessment. | 15 | 16 | 8 | 16 | 16 | 16 |
| Anemia | Blood and lymphatic system disorders | CTCAE 4.0 | Systematic Assessment |
|
| Any Pain | Nervous system disorders | CTCAE 4.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | CTCAE 4.0 | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE 4.0 | Systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | CTCAE 4.0 | Systematic Assessment |
|
| Blood bilirubin Increased | Blood and lymphatic system disorders | CTCAE 4.0 | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | CTCAE 5.0 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | CTCAE 5.0 | Systematic Assessment |
|
| Pain | General disorders | CTCAE 5.0 | Systematic Assessment |
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| Xerostomia | General disorders | CTCAE 5.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | CTCAE 5.0 | Systematic Assessment |
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| Fatigue | General disorders | CTCAE 5.0 | Systematic Assessment |
|
| Transaminase | Blood and lymphatic system disorders | CTCAE 5.0 | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE 5.0 | Systematic Assessment |
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| Weight loss | Metabolism and nutrition disorders | CTCAE 5.0 | Systematic Assessment |
|
| Dizziness | Ear and labyrinth disorders | CTCAE 5.0 | Systematic Assessment |
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| Dyspnea | General disorders | CTCAE 5.0 | Systematic Assessment |
|
| Generalized muscle soreness | Musculoskeletal and connective tissue disorders | CTCAE 5.0 | Systematic Assessment |
|
| Hypocalcemia | Blood and lymphatic system disorders | CTCAE 5.0 | Systematic Assessment |
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| Confusion | General disorders | CTCAE 5.0 | Systematic Assessment |
|
| Increased bilirubin | Blood and lymphatic system disorders | CTCAE 5.0 | Systematic Assessment |
|
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| D005832 |
| Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |