177Lu-PSMA-EB-01 in Patients With Metastatic Castration-resistant Prostate Cancer

Study Overview
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Brief Summary
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This is a pilot study to assess the safety and measure image-based absorbed dose of 177Lu-PSMA-EB-01, a new PSMA-specific radiopharmaceutical, in patients with metastatic castration resistant prostate cancer (mCRPC) who will undergo radioligand therapy (RLT). All patients underwent 68Ga-PSMA and 18F-FDG PET/CT for selection and were randomly divided into three groups of 3 people each.The three groups received an approximately 1.11 GBq (30mCi), 1.85 GBq (50 mCi) and 2.59 GBq (70mCi) of 177Lu-PSMA-EB-01 up to 2 cycles, respectively.

Detailed Description
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Prostate cancer is the most frequent malignant tumor in men worldwide. Prostate-specific membrane antigen (PSMA), is a surface molecule specifically expressed by prostate tumors which was shown to be a valid target for radiotherapy. 177Lu-PSMA-617, a urea-based compound, provide an effective target for the treatment of metastatic castration-resistant prostate cancer. However, a major problem in the therapeutic use of 177Lu-PSMA-617 has been its short half-life and fast rate of clearance. The investigators designed and synthesized a new radiopharmaceutical, named 177Lu-PSMA-EB-01. EB（Evans Blue）can bind to albumin to slow down its plasma clearance rate, thereby increasing tumor accumulation and reducing the total dosage of Lu-177. Hence, EB-PSMA-01 may be an option for consideration due to limited supply of Lu-177, by which more patients may be benefited by this version of 177Lu-EB-PSMA-01. This study was designed to investigate the safety, dosimetry and preliminary effects of 177Lu-EB-PSMA-01 in patients with metastatic castration resistant prostate cancer.

Official Title
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Safety and Dosimetry of 177Lu-PSMA-EB-01 in Patients With Metastatic Castration-resistant Prostate Cancer

Conditions
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Metastatic Castration-resistant Prostate Cancer

Intervention / Treatment
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* Drug: 1.11 GBq (30 mCi) of 177Lu-PSMA-EB-01
* Drug: 1.85 GBq (50 mCi) of 177Lu-PSMA-EB-01
* Drug: 2.59 GBq (70 mCi) of 177Lu-PSMA-EB-01


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: progressive metastatic castration-resistant prostate cancer tumors with high PSMA expression confirmed on 68Ga-PSMA PET/CT Exclusion Criteria: a serum creatinine level of more than 150 μmol per liter a hemoglobin level of less than 10.0 g/dl a white-cell count of less than 4.0× 109/L a platelet count of less than 100 × 109/L a total bilirubin level of more than 3 times the upper limit of the normal range a serum albumin level of more than 3.0 g per deciliter cardiac insufficiency

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1.11 GBq (30 mCi) of 177Lu-PSMA-EB-01<br>All patients were intravenous injected with single dose 1.11 GBq (30 mCi) of 177Lu-PSMA-EB-01 then monitored at 3 hours, 24 hours, 48 hours, 72 hours, and 168 hours post-injection. | Drug: 1.11 GBq (30 mCi) of 177Lu-PSMA-EB-01<br>* All patients were intravenous injected with single dose 1.11 GBq (30 mCi) of 177Lu-PSMA-EB-01 then monitored at 3 hours, 24 hours, 48 hours, 72 hours, and 168 hours post-injection.<br>|
| Experimental: 1.85 GBq (50 mCi) of 177Lu-PSMA-EB-01<br>All patients were intravenous injected with single dose 1.85 GBq (50 mCi) of 177Lu-PSMA-EB-01 then monitored at 3 hours, 24 hours, 48 hours, 72 hours, and 168 hours post-injection. | Drug: 1.85 GBq (50 mCi) of 177Lu-PSMA-EB-01<br>* All patients were intravenous injected with single dose 1.85 GBq (50 mCi) of 177Lu-PSMA-EB-01 then monitored at 3 hours, 24 hours, 48 hours, 72 hours, and 168 hours post-injection.<br>|
| Experimental: 2.59 GBq (70 mCi) of 177Lu-PSMA-EB-01<br>All patients were intravenous injected with single dose 2.59 GBq (70 mCi) of 177Lu-PSMA-EB-01 then monitored at 3 hours, 24 hours, 48 hours, 72 hours, and 168 hours post-injection. | Drug: 2.59 GBq (70 mCi) of 177Lu-PSMA-EB-01<br>* All patients were intravenous injected with single dose 2.59 GBq (70 mCi) of 177Lu-PSMA-EB-01 then monitored at 3 hours, 24 hours, 48 hours, 72 hours, and 168 hours post-injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dosimetry of normal organs and tumors | The semiquantitative dosimetry will be performed based on SPECT/CT acquisitions after the first administration of 177Lu-PSMA-EB-01. The dose delivered to normal organs and tumors will be recorded. | through study completion, an average of 4 weeks | 
| Hematologic adverse events collection | Hematologic status were performed before and every 2 weeks after administration of radiopharmaceutical. Adverse events were categorized using the Common Toxicity Criteria for Adverse Events 5.0 | through study completion, an average of 6 months | 
| Hepatic and renal toxic events collection | Liver function, and renal function were performed before and 4 weeks after administration of radiopharmaceutical. Adverse events were categorized using the Common Toxicity Criteria for Adverse Events 5.0. | through study completion, an average of 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA Response | The serum PSA response was documented semimonthly until 6 weeks after the administration of 177Lu-PSMA-EB-01. PSA response was classified as the following: partial response (PR) if PSA decrease ≥50%, progressive disease (PD) if PSA increase ≥ 25% and stable disease (SD) if PSA increase <25% or PSA decrease <50%. | through study completion, an average of 6 months |