Lu177-EB-PSMA617 Radionuclide Treatment in Patients With Metastatic Castration-resistant Prostate Cancer

Study Overview
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Brief Summary
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In prior studies, the investigators synthesized 177Lu-EB-PSMA-617 by conjugating a truncated Evans Blue (EB) molecule and DOTA chelator onto PSMA-617 and labeled it with 177Lu to increase the tumor accumulation and retention for radioligand therapy，and then the investigators evaluated the dosimetry of 177Lu-EB-PSMA-617 and response to single low-dose treatment in patients with metastatic castration-resistant prostate cancer(mCRPC). This study was performed to evaluate the safety and therapy response to 177Lu-EB-PSMA-617 in patients with mCRPC. This is an open-label, randomized study. Different groups with doses of 1.11GBq (30 mCi), 2.00 GBq (54 mCi) and 3.7GBq (100 mCi)of 177Lu-EB -PSMA617 will be injected intravenously. All patients will undergo 68Ga-PSMA PET/CT scans before and after the treatment.

Detailed Description
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Prostate cancer (PC) is the second most common cancer worldwide in men, with persistently high numbers dying from this disease. Recent studies have demonstrated the possibility of 177Lu-PSMA-617 therapy as a viable treatment option in mCRPC. To increase tumor accumulation and retention for radioligand therapy, and reduce dosage of 177Lu, the investigators conjugated a truncated Evans blue (EB) molecule and DOTA chelator onto PSMA-617 (EB-PSMA-617) and label it with 177Lu. The study is open-label and patients will be divided into three groups and monitored throughout the 6 to 10-month treatment period for survival, disease progression, and adverse events to evaluate the safety and therapy response to the 177Lu-EB-PSMA-617.

Official Title
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Lu177-EB-PSMA617 Prostate-Specific Membrane Antigen Inhibitor Therapy in Patients With Castration-Resistant Prostate Cancer

Conditions
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Metastatic Castration-resistant Prostate Cancer

Intervention / Treatment
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* Drug: 1.11GBq of 177Lu-EB-PSMA-617
* Drug: 2.00 GBq of 177Lu-EB-PSMA-617
* Drug: 3.70GBq of 177Lu-EB-PSMA-617


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: progressive metastatic castration-resistant prostate cancer that did not respond to androgen-suppression therapy and/or systemic chemotherapy. Distant metastases with high PSMA expression confirmed by 68Ga-PSMA PET/CT within one week before the injection of 177Lu-EB-PSMA-617. Exclusion Criteria: a serum creatinine level of more than 150μmol 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 including carcinoid heart valve disease, a severe allergy or hypersensitivity to radiographic contrast material, claustrophobia, and pregnancy or breastfeeding.

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: 1.11GBq of 177Lu-EB-PSMA-617<br>The patients were intravenously injected with the dose about 1.11GBq (30 mCi) of 177Lu-EB-PSMA617 and underwent 68Ga-PSMA PET/CT scans before and after the treatment. | Drug: 1.11GBq of 177Lu-EB-PSMA-617<br>* Patients were intravenous injected with the dose about 1.11GBq (30 mCi) of 177Lu-EB-PSMA-617 every 8 weeks (±1 week) for a maximum of 3 cycles.<br>|
| Experimental: 2.00 GBq of 177Lu-EB-PSMA-617<br>The patients were intravenously injected with the dose about 2.00 GBq (54 mCi) of 177Lu-EB-PSMA-617 and underwent 68Ga-PSMA PET/CT scans before and after the treatment. | Drug: 2.00 GBq of 177Lu-EB-PSMA-617<br>* Patients were intravenous injected with the dose about 2.00 GBq (54 mCi) of 177Lu-EB-PSMA-617 every 8 weeks (±1 week) for a maximum of 3 cycles.<br>|
| Experimental: 3.70GBq of 177Lu-EB-PSMA-617<br>The patients were intravenously injected with the dose about 3.70GBq (100 mCi) of 177Lu-EB-PSMA617 and underwent 68Ga-PSMA PET/CT scans before and after the treatment. | Drug: 3.70GBq of 177Lu-EB-PSMA-617<br>* Patients were intravenous injected with the dose about 3.70GBq (100 mCi) of 177Lu-EB-PSMA-617 every 8 weeks (±1 week) for a maximum of 3 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the PSA and standardized uptake value of 68Ga-PSMA before and after the treatment in mCRPC | The semiquantitative analysis will be performed by the same person for all the cases, and the standardized uptake in lesions will be measured. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events collection | Adverse events after the treatment of patients will be followed and assessed | patients will be monitored throughout the whole treatment period. Patients will be followed up every 3 month until 1 year for a long-term follow-up period. |