Targeted Alpha Therapy With 225Actinium-PSMA-I&T of Castration-resISTant Prostate Cancer (TATCIST).
Study Details
Study Description
Brief Summary
The treatment regimen will consist of 4 doses of 225Ac-PSMA-I&T
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
The therapy is administered at 8 ± 1week intervals, with the initial activity of 100 kBq/kg (±10%), then de-escalation to 87 kBq/kg (±10%), 75 kBq/kg (±10%) or 50 kBq/kg (±10%) in cases of good response (PSA decline >50%). The route of administration will be Intravenous (I.V.) infusion over approximately 1-3 minutes.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ac225-PSMA I&T All patients will receive 225Ac-PSMA-I&T, administered at 8 ± 1-week interval, with the initial activity of 100 kBq/kg (±10%), then de-escalation to 87 kBq/kg (±10%), 75 kBq/kg (±10%) or 50 kBq/kg (±10%) in cases of good response (PSA decline >50%), at the discretion of the principal investigator. |
Drug: Ac225-PSMA I&T
Peptide capable of binding to the domain of PSMA radiolabeled with Ac225
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Determination of the efficacy after 225Ac-PSMA-I&T in patients with metastatic castration-resistant prostate cancer with RLT refractory or without prior 177 Lu-PSMA-617. [24 months after last dose administration]
The efficacy is defined by measurement of PSA level and more than 50% decline after 225Ac-PSMA-I&T. MRI scans of the abdomen and pelvis with and without contrast, CT of the chest with contrast only, and bone scan will be performed at baseline, before each treatment, and every 3 months after last treatment until the last follow up.
- Determination of the safety after 225Ac-PSMA-I&T by measuring changes in the level of alkaline phosphatase (ALT) in patients with prostate cancer [24 months after last dose administration]
Safety measured by determination of notable changes in Alkaline phosphatase (ALP) levels ([ULN] done before therapy and every week for the first 8 weeks after the first treatment and every 2 weeks during the rest of the treatments and every month after the last treatment until completion of follow-up or patient progression.
- Determination of the safety after 225Ac-PSMA-I&T by measuring changes in the level of alkaline transferase (AST) in patients with prostate cancer [24 months after last dose administration]
Safety measured by determination of notable changes in Alkaline transferase (AST) levels ([ULN] done before therapy and every week for the first 8 weeks after the first treatment and every 2 weeks during the rest of the treatments and every month after the last treatment until completion of follow-up or patient progression.
- Determination of the safety after 225Ac-PSMA-I&T by measuring changes in the level of creatinine clearance in patients with prostate cancer [24 months after last dose administration]
Safety measured by determination of the notable changes in creatinine clearance [mL/min] done before therapy and every week for the first 8 weeks after the first treatment and every 2 weeks during the rest of the treatments and every month after the last treatment until completion of follow-up or patient progression.
Secondary Outcome Measures
- Determination of the maximum PSA decline after all cycles of therapy with 225Ac-PSMA-I&T. [24 months after last dose administration]
The PSA [ng/ml] level will be measured at baseline after all cycles of treatment
- Determination of PSA progression-free survival (PFS) [24 months after last dose administration]
Progression -free survival will be measured in months from start of therapy until death or PSA progression.
- Determination of duration of response [24 months after last dose administration]
It will be measured from the first date of complete response or partial response based on RECIST 1.1/PCWG3 criteria or death in the absence of progression
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Signing informed consent
-
Adenocarcinoma of Prostate proven by histopathology
-
Life expectancy of 6 months or more
-
Unresectable metastases
-
Progressive disease, with docetaxel/cabazitaxel or declined taxane therapy by the patient
-
177Lu-PSMA-617 naive or 177Lu-PSMA-617/177Lu-PSMA-I&T treated
-
If BRCA mutations or microsatellite instability is present, patients should have received FDA approved therapies such as PARP inhibitors and pembrolizumab, and progressed
-
Castration-resistant disease with confirmed testosterone level ≤50 ng/ml under prior androgen deprivation therapy (ADT)
-
Positive 68Ga-PSMA-11 PET/CT for the majority of measurable diseases defined as SUV ≥2.0
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ECOG 0-2
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Hemoglobin concentration ≥ 9.0 g/dL
-
Platelet counts ≥100 × 109/L
-
White blood cell count ≥ 2.0 × 109/L), ANC>1.5 x109/L
-
Glomerular Filtration Rate (GFR) ≥ 60 ml/min
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AST and ALT ≤ 5xULN
-
Billirubin ≤ 3x ULN
-
Albumin ≥ 25 g/L
-
Serum/plasma creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min based on Cockcroft-Gault formula
-
Received at least one ARAT in the past
-
Patients on anti-androgen therapy are allowed to continue their treatment at the discretion of their oncologists
Exclusion Criteria:
-
Inclusion Criteria:
-
Signing informed consent.
-
Adenocarcinoma of Prostate proven by histopathology
-
Life expectancy of 6 months or more.
-
Unresectable metastases.
-
Progressive disease, with docetaxel/cabazitaxel or declined taxane therapy by the patient.
-
177Lu-PSMA-617 naive or 177Lu-PSMA-617/177Lu-PSMA-I&T treated.
-
If BRCA mutations or microsatellite instability is present, patients should have received FDA approved therapies such as PARP inhibitors and pembrolizumab, and progressed
-
Castration resistant disease with confirmed testosterone level ≤50 ng/mlunder prior androgen deprivation therapy (ADT)
-
Positive 68Ga-PSMA-11 PET/CT for the majority of measurable disease defined as SUV ≥2.0.
-
ECOG 0-2
-
Hemoglobin concentration ≥ 9.0 g/dL
-
Platelet counts ≥100 × 109/L
-
White blood cell count ≥ 2.0 × 109/L), ANC>1.5 x109/L
-
Glomerular Filtration Rate (GFR) ≥ 60 ml/min
-
AST and ALT ≤ 5xULN
-
Billirubin ≤ 3x ULN
-
Albumin ≥ 25 g/L.
-
Serum/plasma creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min based on Cockcroft-Gault formula
-
Received at least one ARAT in the past.
-
Patients on anti-androgen therapy are allowed to continue their treatment at the discretion of their oncologists.
Exclusion Criteria:
-
Less than 6 weeks since last myelosuppressive therapy (including Docetaxel, Cabazitaxel, 223Ra, 153Sm, 177Lu-PSMA-617, 177Lu-PSMA-I&T) or other radionuclide therapy permitted (including 223Ra, 153Sm)
-
Urinary tract obstruction as evidenced by Tc-99m DTPA renal scan with diuretics
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Abnormal renal function (eGFR <60 mL/min), baseline Hgb <9g/dL, ANC<1.5 x109/L, platelets <100 x109/L, and PT, INR or PTT ≥1.5xULN
-
Persistent baseline dry eye or dry mouth from prior RLT
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Persistent prior AEs >Grade 1 from prior anti-cancer therapies
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Administration of an investigational agent ≤60 days or 5 half-lives, whichever is shorter, prior to randomization
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The known presence of central nervous system metastases
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Active malignancy other than low-grade non-muscle-invasive bladder cancer and non-melanoma skin cancer
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Concurrent illness that may jeopardize the patient's ability to undergo study procedures.
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Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
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Concurrent serious (as determined by the investigator) medical conditions, including, but not limited to, New York Heart Association class III or IV congestive heart failure
-
Major surgery ≤30 days prior to randomization
-
Planning to conceive pregnancy during the treatment and up to 6 months after the last treatment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Excel Diagnostics and Nuclear Oncology Center | Houston | Texas | United States | 77042 |
Sponsors and Collaborators
- Excel Diagnostics and Nuclear Oncology Center
Investigators
- Principal Investigator: Rodolfo Nunez, MD, Excel Diagnostics and Nuclear Oncology Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 156903