Clinical trial NCT03780075: Lu177-EB-PSMA617 Radionuclide Treatment in Patients With Metastatic Castration-resistant Prostate Cancer
Official title: Lu177-EB-PSMA617 Prostate-Specific Membrane Antigen Inhibitor Therapy in Patients With Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Metastatic Castration-resistant Prostate Cancer
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: National Institute for Biomedical Imaging and Bioengineering (NIBIB)
First posted: 2018-12-19
Enrollment: 50
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change of the PSA and standardized uptake value of 68Ga-PSMA before and after the treatment in mCRPC
timeFrame: 1 year
Secondary outcomes:
measure: Adverse events collection
timeFrame: 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.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
Study officials:
affiliation: Peking Union Medical College Hospital, Chinese Academy of Medical Science
name: Zhaohui Zhu, MD,PHD
role: STUDY_CHAIR
References: