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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Castration-resistant Prostate Cancer
• Intervention / Treatment: 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

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jie Zang, MD; Phone Number: +86 10 69154196; Email: 15901495106@163.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking Union Medical College Hospital
    • Contact: Jie Zang, MD; Email: 15901495106@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1.11GBq of 177Lu-EB-PSMA-617; 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; 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.
Experimental: 2.00 GBq of 177Lu-EB-PSMA-617; 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; 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.
Experimental: 3.70GBq of 177Lu-EB-PSMA-617; 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; 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.

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: National Institute for Biomedical Imaging and Bioengineering (NIBIB)
• Investigators: Study Chair: Zhaohui Zhu, MD,PHD, Peking Union Medical College Hospital, Chinese Academy of Medical Science

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2018
• Primary Completion (Actual): September 1, 2020
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: December 17, 2018
• First Submitted That Met QC Criteria: December 17, 2018
• First Posted (Actual): December 19, 2018

Study Record Updates

• Last Update Posted (Actual): May 12, 2022
• Last Update Submitted That Met QC Criteria: May 6, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; 177Lu-EB-PSMA-617
• Other Study ID Numbers: PekingUMCH-NM019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No