An Open-Label, Non-Randomized, Single-Center, Investigator-Initiated Trial to Determine the Safety, Dosimetry, and Preliminary Effectiveness of 177Lu-Dansyl-PSMA in Patients With Metastatic Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Incidence of treatment-related adverse events (safety and tolerability)
研究概览
简要总结
Ten to 20% of patients with prostate cancer (PC) experience progression in their disease, even after undergoing pharmaceutical or surgical castration, leading to metastatic CRPC (mCRPC). Prostate-specific membrane antigen (PSMA) is a membrane-bound glycoprotein mostly specific to the prostate. While PSMA is expressed at low levels in normal prostate, this expression increased by 100-1000-fold in PC, which makes it a favorable target for therapy. This study was designed to evaluate the safety, tolerability, and maximum tolerated dose of a long-lasting radiolabeled ligand 177Lu-Dansyl-PSMA in mCRPC patients.
详细描述
This proposal is a phase I, open-label study of escalating doses of 177Lu-Dansyl-PSMA Injection in patients with PSMA-positive mCRPC. The initial dose of 177Lu-Dansyl-PSMA is 1.85GBq (50 mCi), and subsequent cohorts receive an incremental 50% dose increase until dose-limiting toxicity (DLT) is observed. Treatment is planned for up to 2 cycles, and the time interval between cycles is 6 weeks. The primary endpoint assessed the safety and maximum tolerated dose of 177Lu-Dansyl-PSMA used for radioligand therapy in patients with PSMA-positive mCRPC. Secondary endpoints included dosimetry and determination of the preliminary treatment efficacy of 177Lu-Dansyl-PSMA.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Ability to understand and willingness to sign a written informed consent document.
- •Age 21 and older
- •Confirmed unresectable PC that is refractory to or has progressed following prior treatments.
- •Confirmed unresectable PC with measurable disease per RECIST (version 1.1) (i.e. at least 1 lesion > 1 cm or lymph node > 1.5 cm in short axis)
- •Patients must have a castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L).
- •Eastern Cooperative Oncology Group Performance Status ≤ 3
- •Participant must have completed prior therapy at least 2 weeks (washout period) before 68Ga-PSMA PET/CT scan. Any clinically significant toxicity (with the exceptions of hair loss and sensory neuropathy) related to prior therapy resolved below Grade 2 or baseline. Completion of entry into 68Ga-PSMA study and completion of the scan
- •Patients must be 68Ga-PSMA PET/CT scan positive.
- •Hematologic parameters defined as:
- •Absolute neutrophil count (ANC) ≥ 1000 cells/mm3 Platelet count ≥ 50,000/mm3 Hemoglobin ≥ 8 g/dL
- •Blood chemistry levels defined as:
- •AST, ALT, alkaline phosphatase ≤ 5 times upper limit of normal (ULN) Total bilirubin ≤ 3 times ULN Creatinine ≤ 3 times ULN Able to remain motionless for up to 30-60 minutes per scan
排除标准
- •Participant on any chemical anticoagulant including antiplatelet agents (excluding ASA)
- •Participants with Class 3 or 4 NYHA Congestive Heart Failure
- •Clinically significant bleeding within two weeks before trial entry (e.g. gastrointestinal bleeding, intracranial bleeding)
- •Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (i.e. larger than what is required for placement of a central venous access, percutaneous feeding tube, or biopsy) within 28 days before study day 1 or anticipated surgery within the subsequent 6 weeks
- •Has an additional active malignancy requiring therapy within the past 2 years
- •Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
- •Psychiatric illness/social situations that would interfere with compliance with study requirements
- •Cannot undergo PET/CT scanning because of weight limits (350 lbs)
- •INR>1.2; PTT>5 seconds above UNL
研究组 & 干预措施
177Lu-Dansyl-PSMA
177Lu-Dansyl-PSMA A maximum of 2 cycles of 50 mCi (1.85 GBq) 177Lu-Dansyl-PSMA, each. Route of administration: Slow intravenous infusion/injection (i.v.) Duration of treatment: 2 cycles, every 6 weeks. Subsequent cohorts received an incremental 50% dose increase until dose-limiting toxicity (DLT) was observed.
干预措施: 177Lu-Dansyl-PSMA radioligand therapy (Drug)
结局指标
主要结局
Incidence of treatment-related adverse events (safety and tolerability)
时间窗: At the end of Cycle 2 (each cycle is 42 days)
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0. Dose-limiting toxicity was defined as any 177Lu-Dansyl-PSMA-related AE ≥ grade 3 (G3).
To determine the maximum tolerated dose (MTD)
时间窗: At the end of Cycle 2 (each cycle is 42 days)
The MTD is the dose level below that which 2 out of 6 subjects in a cohort have DLT
次要结局
- Dosimetry(At the end of Cycle 1 (each cycle is 42 days))