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

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Unknown; Phase 1

Conditions: Metastatic Castration-resistant Prostate Cancer

Treatments: Drug: 2.00 GBq of 177Lu-EB-PSMA-617; Drug: 3.70GBq of 177Lu-EB-PSMA-617; Drug: 1.11GBq of 177Lu-EB-PSMA-617

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03780075

PekingUMCH-NM019

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 50 estimated patients

Sex: Male

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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50 participants in 3 patient groups

1.11GBq of 177Lu-EB-PSMA-617

Experimental group

Description:

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.

Treatment:

Drug: 1.11GBq of 177Lu-EB-PSMA-617

2.00 GBq of 177Lu-EB-PSMA-617

Experimental group

Description:

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.

Treatment:

Drug: 2.00 GBq of 177Lu-EB-PSMA-617

3.70GBq of 177Lu-EB-PSMA-617

Experimental group

Description:

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.

Treatment:

Drug: 3.70GBq of 177Lu-EB-PSMA-617