Phase 2 Study of Terbium 161 PSMA in Lutetium-177 PSMA Naive mCRPC Patients
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 60
- 试验地点
- 4
- 主要终点
- Objective response evaluation
研究概览
简要总结
In this study it is aimed to analyze the efficacy and safety of Tb-161 PSMA I&T in the 7.4 GBq activity in a large patient group of Lu-177 PSMA naïve mCRPC patients. 3 cycles of Tb-161 PSMA will be administered with 6 weeks periods. After each cycle a triple bed quantitative single photon emission CT (SPECT)-CT scan from vertex to thigh will be acquired 24 h after every treatment of Tb-161 PSMA. In the first cycle additional time points SPECT-CT acquisitions will be obtained for dosimetric calculations. Details of dosimetry acquisitions will be provided by dosimetry partner. Routine safety blood tests including full blood counts, liver function test, electrolytes, serum PSA, and assessment for adverse events were performed every 3 weeks during study treatment. Once the patient completed three cycles of Tb-161 PSMA, they will continue to undergo clinical review, assessment for adverse events, routine safety bloods, and PSA every 6 weeks for 48 weeks. OR to treatment will be assessed by Ga-68 PSMA PET/CT using RECIP 1.0 criteria.
详细描述
Radionuclide treatment with Lutetium-177 (Lu-177)-labelled prostate-specific membrane antigen (PSMA) has become a standard care of treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). Main advantages of Lu-177 PSMA improvement of overall survival and quality of life. Progression of disease occurs most of the patients after Lu-177 PSMA treatment. For this reason, labelling of PSMA with other radionuclides such as alfa or Auger electrons emitters have been a subject of interest. The major advantage of Terbium-161 is, besides the beta-radiation similar to Lu-177, its additional emission of Auger electron. Additional energy arising from Auger electrons has a shorter distance. Thus, higher concentration of radiation affects micrometastatic deposits of prostatic cancer due to cause of double-strand DNA damage. Preclinical studies demonstrated superior anti-tumor activity of Tb-161 PSMA compared with the Lu-177 PSMA. Furthermore, safety of Tb-161 I&T has been documented recently with VIOLET trial as the first in human study.
In this study it is aimed to analyze the efficacy and safety of Tb-161 PSMA I&T in the 7.4 GBq activity in a large patient group of Lu-177 PSMA naïve mCRPC patients.
3 cycles of Tb-161 PSMA will be administered with 6 weeks periods. After each cycle a triple bed quantitative single photon emission CT (SPECT)-CT scan from vertex to thigh will be acquired 24 h after every treatment of Tb-161 PSMA. In the first cycle additional time points SPECT-CT acquisitions will be obtained for dosimetric calculations. Details of dosimetry acquisitions will be provided by dosimetry partner.
Routine safety blood tests including full blood counts, liver function test, electrolytes, serum PSA, and assessment for adverse events were performed every 3 weeks during study treatment. Once the patient completed three cycles of Tb-161 PSMA, they will continue to undergo clinical review, assessment for adverse events, routine safety bloods, and PSA every 6 weeks for 48 weeks.
Ga-68-PSMA and F-18-FDG PET-CT will be repeated at 8 weeks after last cycle. During cycles if any progression is observed in posttreatment SPECT/CT imaging or PSA levels, additional Ga-68-PSMA and F-18-FDG PET-CT scans will be performed. If disease progression is confirmed, then treatment will be ceased.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Men aged 18 years or older with mCRPC (histologically or cytologically confirmed adenocarcinoma of the prostate)
- •Progressive disease as defined by the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) under previous treatment with taxane chemotherapy (unless medically unsuitable) and at least one second-generation androgen receptor pathway inhibitor (ARPI)
- •Adequate bone marrow, hepatic, and renal function
- •Eastern Cooperative Oncology Group performance status of 0-2;
- •A life expectancy of at least 6 months.
- •On Ga-68 PSMA PET/CT, a maximum standardised uptake value (SUVmax) of at least 20 in at least one metastasis and SUVmax of at least 10 in measurable soft tissue metastases.
- •Patient has provided written informed consent
- •PSA progression: minimum of 2 rising PSA values from baseline measurement with interval of ≥1 wk between each measurement
- •Soft-tissue progression: per RECIST 1.1
- •Bone progression: ≥2 new lesions on bone scan
- •At least 3 wk interval since completion of surgery or radiotherapy before registration
排除标准
- •Patients with discordant metastases defined as positive on 2-[¹⁸F]fluoro-2-deoxy-D-glucose (FDG) PET-CT with minimal uptake on Ga-68-PSMA PET-CT
- •Previous treatment with another radioisotope
- •Other malignancies within the previous 2 years before registration other than basal cell or squamous cell carcinomas of skin or other cancers that are unlikely to recur within 24 months
- •Concurrent illnesses that could jeopardise the ability of the patient to undergo the trial procedures.
- •Patient has symptomatic brain metastases or leptomeningeal metastases
- •Patient has symptomatic or impending cord compression unless appropriately treated beforehand and clinically stable for >4 wk
研究组 & 干预措施
Tb-161 PSMA treatment arm
Patients who will treat with 3 cycles of Tb-161 PSMA with 7.4 GBq activity
干预措施: Terbium 161- PSMA I&T (Drug)
结局指标
主要结局
Objective response evaluation
时间窗: up to 6 weeks after last cycle of treatment (each cycle is 1 day)
Response to treatment will be assessed by Ga-68 PSMA PET/CT using RECIP 1.0 criteria.
PSA response evaluation
时间窗: within three weeks after each treatment cycle and with 6 weeks periods from 6 to 48 weeks after last cycle (each cycle is 1 day)
At least 50% change in the serum PSA levels
Change in QoL
时间窗: within 1 months after each cycles (each cycle is 1 day)
Change in QoL will be evaluated by change in scores of the Functional Assessment of Cancer Therapy for Prostate (FACTP) questionnaire for treatment-specific symptoms.
Toxicity Evaluation
时间窗: within three weeks after each treatment and with 6 weeks period within 6 to 48 weeks after last cycle (each cycle is 1 day)
To analyze the organ toxicities of Tb-161 PSMA treatment with 7.4 GBq activity in 3 cycles with Common Terminology Criteria for Adverse Events (CTCAE) scores
次要结局
- Tumor absorbed dose calculations(within 96 hours after first cycle (each cycle is 1 day))
- Organ absorbed dose calculations(within 96 hours after first cycle (each cycle is 1 day))
研究者
Cigdem Soydal
Prof of Nuclear Medicine
Ankara University