Clinical trial NCT04996602: Therapeutic Efficiency and Response to 2.0 GBq (55mCi) 177Lu-EB-PSMA in Patients With mCRPC
Official title: Therapeutic Efficiency and Response to 2.0 GBq (55mCi) 177Lu-EB-PSMA in Patients With mCRPC
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Prostate Cancer
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2021-08-09
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In recent years, quite a few studies have demonstrated the possibility of 177Lu-PSMA-617 therapy as a viable treatment option in metastatic castration resistant prostate cancer (mCRPC), which has been shown desired effect. To increase tumor accumulation and retention for radioligand therapy, and reduce dosage of 177Lu, we conjugated a truncated Evans blue (EB) molecule and DOTA chelator onto PSMA-617 (EB-PSMA) and labeled it with 177Lu. This study is designed to assess the efficiency and response to 177Lu-EB-PSMA (55 mCi) in patients with mCRPC.

Detailed description: Prostate cancer is one of the most common cancers and the second most frequent cause of cancer deaths for adult men. With the advances in the diagnosis and treatment of prostate cancer, some patients with localized prostate cancer can achieve good curative results, but there are still 10%～20% of patients progress to metastatic castration-resistant prostate cancer (mCRPC) every year, only one third of patients with mCRPC survive more than five years. Radioligand therapy targeting prostate specific membrane antigen (PSMA), which is overexpressed in most prostate cancer and even further increased in metastatic and castration-resistant carcinomas, has been demonstrated as an effective and safe therapy in men with mCRPC. 177Lu-PSMA-617 has also shown desired effect. However, 177Lu-PSMA-617, as a small molecule imaging agent, is cleared very quickly from the circulation. Therefore, radiotherapy that is based on small molecules requires high doses and frequent administrations, leading to systemic toxicity. 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) and labeled it with 177Lu. The investigators have published some articles demonstrated 177Lu-EB-PSMA had much higher accumulation in prostate cancer lesions than 177Lu-PSMA-617 and also showed an ideal effect. This study is designed to assess the efficiency and response to 177Lu-EB-PSMA (55 mCi) in patients with mCRPC.

Eligibility criteria: Inclusion Criteria:

* All the patients had progressive metastatic castration-resistant prostate cancer that did not respond to androgen-suppression therapy and/or systemic chemotherapy;
* Distant metastases with high PSMA expression were confirmed on 68Ga-PSMA PET/CT within one week before the injection of 177Lu-EB-PSMA.

Exclusion Criteria:

* The exclusion criteria were 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 and 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.

Primary outcomes:
measure: Therapeutic effect: PSA Response
timeFrame: through study completion, an average of 1 month
measure: Therapeutic effect: 68Ga-PSMA PET/CT Response
timeFrame: through study completion, an average of 2 months
Secondary outcomes:
measure: Adverse events collection: Blood tests
timeFrame: through study completion, an average of 1 month
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Zhaohui Zhu, MD
role: PRINCIPAL_INVESTIGATOR
References: