Comparison of 177Lu-PSMA-617 and 225Ac-PSMA-617 in a Prostatectomy Model (LUTACT Trial)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Thomas Hope
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Mean of tumor absorbed dose (Cohorts 1 and 2)
研究概览
简要总结
There is evidence that Actinium-225 Prostate-Specific Membrane Antigen (225Ac-PSMA) has a potentially higher level of efficacy than 177 Lutetium Prostate-Specific Membrane Antigen (177Lu-PSMA) as a radioligand therapy. This single center, pilot study will compare differences in the mechanisms of actinium-225 and lutetium-177 radioligand therapies (RLT) in participants with high or very high risk localized or locoregional prostate cancer planning on undergoing a prostatectomy.
详细描述
PRIMARY OBJECTIVES:
- Compare the tumor absorbed dose between 177Lu-PSMA-617 and 225Ac-PSMA-617.
- Compare the immunologic priming of 177Lu-PSMA-617 and 225Ac-PSMA-617 with controls in prostatectomy specimens.
SECONDARY OBJECTIVES:
- Determine the safety and tolerability of neoadjuvant 177Lu-PSMA-617 and 225Ac-PSMA-617 in participants with high or very high-risk prostate cancer planning to undergo radical prostatectomy.
- Estimate PSA response for 177Lu-PSMA-617 and 225Ac-PSMA-617 treatment.
- Estimate the rate of pathologic response in participants treated with 177Lu-PSMA-617 and 225Ac-PSMA-617.
EXPLORATORY OBJECTIVES:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Age ≥18 years.
- •Histologically confirmed prostate adenocarcinoma.
- •High-risk disease as defined as meeting 1 or more of the 3 following criteria:
- •Gleason score of 4+4 disease or higher, Or Gleason 4+3 with large cribriform component (defined as >0.25 mm in short diameter)
- •Pelvic nodal metastases on PSMA PET.
- •Extracapsular extension or seminal vesicle invasion on MRI or PSMA PET.
- •No evidence of distant metastatic disease as determined by PSMA PET. Nodal disease at or below the iliac bifurcation (clinical stage N1) is allowed.
- •Maximum Standardized Uptake Value (SUVmax) in the primary tumor greater than 10 on PSMA PET using Gallium-68 (68Ga)-PSMA-11 or piflufolastat F 18 (18F-DCFPyL).
- •*Note: this applies to treatment cohorts only; there are no SUV requirements for tissue-only cohorts (Control Group).
- •Target tumor in the prostate measuring greater than 1.0 cm on MRI.
- •Willing to undergo prostatectomy with or without lymph node dissection, and candidate for prostatectomy as determined by urologic oncology.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%),
- •Demonstrates adequate organ function as defined below:
- •Platelets ≥100,000/mcL, independent of transfusions or growth factors within 3 months of treatment start.
- •Hemoglobin ≥10 g/dL, independent of transfusions or growth factors within 3 months of treatment start.
- •Absolute Neutrophil Count (ANC) ≥1,500/microliter (mcL).
- •Creatinine clearance Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m^2 , calculated using the Cockcroft-Gault equation.
- •Albumin ≥2.5 g/dL.
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0 x ULN.
- •Total bilirubin (TBIL) ≤2 x the institutional upper limit of normal (ULN). For participants with known Gilbert's Syndrome ≤3 x ULN is permitted.
- •Note: this applies to treatment cohorts only; there are no requirements for tissue-only cohorts (Control Group)
- •Ability to understand and the willingness to sign a written informed consent document.
- •Participants must provide consent to comply to recommended radioprotection precautions during study.
- •Participants must use adequate contraception and not donate sperm while on study drug and for at least 14 weeks after the last study treatment.
排除标准
- •Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, participants with a prior history of malignancy that has been adequately treated and who have been disease- free, treatment- free for more than 3 years prior to randomization, or participants with adequately treated non-melanoma skin cancer, superficial bladder cancer are eligible.
- •Individuals with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
- •Concurrent and serious (as determined by the principal investigator) medical conditions, including, but not limited to New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, known active hepatitis B or C or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation.
- •Has received prior prostate cancer therapy.
- •a. Prior 5-alpha reductase inhibitors (e.g. finasteride, dutasteride) allowed if discontinued at least 3 weeks prior to treatment start.
- •Has participated in a study of an investigational therapeutic product and received study treatment or used an investigational device within four weeks of the first dose of treatment.
- •Prior external beam radiation therapy (EBRT) to the prostate or prostate bed.
- •Dry mouth that impacts the eating of food (i.e., requiring fluids prior to eating)
- •Additional exclusion criteria applicable only to participants undergoing intraarterial administration of PSMA RLT:
- •Severe allergy to iodinated contrast.
- •Severe atherosclerosis from prior CT imaging study, or greater than 10 pack-year smoking history if no prior imaging available.
研究组 & 干预措施
Control Group (Prostatectomy only)
Participants will obtain a non-investigational prostatectomy. Tumor tissue obtained at the time of surgery will be utilized for comparisons with the cohorts receiving study therapies. All participants will undergo prostatectomy four weeks after completing radioligand therapy and will be followed up 6 weeks after surgery for safety assessments and up to 24 months after surgery.
干预措施: Non-investigational, Prostatectomy (Procedure)
Control Group (Prostatectomy only)
Participants will obtain a non-investigational prostatectomy. Tumor tissue obtained at the time of surgery will be utilized for comparisons with the cohorts receiving study therapies. All participants will undergo prostatectomy four weeks after completing radioligand therapy and will be followed up 6 weeks after surgery for safety assessments and up to 24 months after surgery.
干预措施: Prostate Tissue Collection (Procedure)
Cohort 1 (177Lu-PSMA-617)
Five participants will receive a single dose of 177Lu-PSMA-617 radioligand therapy intravenously (IV), five participants will receive a single dose of 177Lu-PSMA-617 intra-arterially (IA), and five participants will receive two doses over 6 weeks intravenously. In participants receiving two doses, the dose will be divided so that the cumulative dose will be equivalent to participants receiving a single dose. All participants will undergo prostatectomy four weeks after completing radioligand therapy and will be followed up 6 weeks after surgery for safety assessments and at 3, 6, 12, 36, 48, and 60 months for long-term outcomes.
干预措施: Blood Sample Collection (Procedure)
Cohort 1 (177Lu-PSMA-617)
Five participants will receive a single dose of 177Lu-PSMA-617 radioligand therapy intravenously (IV), five participants will receive a single dose of 177Lu-PSMA-617 intra-arterially (IA), and five participants will receive two doses over 6 weeks intravenously. In participants receiving two doses, the dose will be divided so that the cumulative dose will be equivalent to participants receiving a single dose. All participants will undergo prostatectomy four weeks after completing radioligand therapy and will be followed up 6 weeks after surgery for safety assessments and at 3, 6, 12, 36, 48, and 60 months for long-term outcomes.
干预措施: 177 Lutetium Prostate-Specific Membrane Antigen 617 (Drug)
Cohort 1 (177Lu-PSMA-617)
Five participants will receive a single dose of 177Lu-PSMA-617 radioligand therapy intravenously (IV), five participants will receive a single dose of 177Lu-PSMA-617 intra-arterially (IA), and five participants will receive two doses over 6 weeks intravenously. In participants receiving two doses, the dose will be divided so that the cumulative dose will be equivalent to participants receiving a single dose. All participants will undergo prostatectomy four weeks after completing radioligand therapy and will be followed up 6 weeks after surgery for safety assessments and at 3, 6, 12, 36, 48, and 60 months for long-term outcomes.
干预措施: Non-investigational, Prostatectomy (Procedure)
Cohort 1 (177Lu-PSMA-617)
Five participants will receive a single dose of 177Lu-PSMA-617 radioligand therapy intravenously (IV), five participants will receive a single dose of 177Lu-PSMA-617 intra-arterially (IA), and five participants will receive two doses over 6 weeks intravenously. In participants receiving two doses, the dose will be divided so that the cumulative dose will be equivalent to participants receiving a single dose. All participants will undergo prostatectomy four weeks after completing radioligand therapy and will be followed up 6 weeks after surgery for safety assessments and at 3, 6, 12, 36, 48, and 60 months for long-term outcomes.
干预措施: Prostate Tissue Collection (Procedure)
Cohort 1 (177Lu-PSMA-617)
Five participants will receive a single dose of 177Lu-PSMA-617 radioligand therapy intravenously (IV), five participants will receive a single dose of 177Lu-PSMA-617 intra-arterially (IA), and five participants will receive two doses over 6 weeks intravenously. In participants receiving two doses, the dose will be divided so that the cumulative dose will be equivalent to participants receiving a single dose. All participants will undergo prostatectomy four weeks after completing radioligand therapy and will be followed up 6 weeks after surgery for safety assessments and at 3, 6, 12, 36, 48, and 60 months for long-term outcomes.
干预措施: Single-photon emission computed tomography (SPECT)/Computerized tomography (CT) (Procedure)
Cohort 2 (225Ac-PSMA-617)
Five participants will receive a single dose of 225Ac-PSMA-617 radioligand therapy IV, five participants will receive a single dose of 225Ac-PSMA-617 IA, and five participants will receive two doses over 6 weeks IV. In participants receiving two doses, the dose will be divided so that the cumulative dose will be equivalent to participants receiving a single dose. All participants will undergo prostatectomy four weeks after completing radioligand therapy and will be followed up 6 weeks after surgery for safety assessments and at 3, 6, 12, 36, 48, and 60 months for long-term outcomes.
干预措施: Actinium-225 Prostate-Specific Membrane Antigen 617 (Drug)
Cohort 2 (225Ac-PSMA-617)
Five participants will receive a single dose of 225Ac-PSMA-617 radioligand therapy IV, five participants will receive a single dose of 225Ac-PSMA-617 IA, and five participants will receive two doses over 6 weeks IV. In participants receiving two doses, the dose will be divided so that the cumulative dose will be equivalent to participants receiving a single dose. All participants will undergo prostatectomy four weeks after completing radioligand therapy and will be followed up 6 weeks after surgery for safety assessments and at 3, 6, 12, 36, 48, and 60 months for long-term outcomes.
干预措施: Non-investigational, Prostatectomy (Procedure)
Cohort 2 (225Ac-PSMA-617)
Five participants will receive a single dose of 225Ac-PSMA-617 radioligand therapy IV, five participants will receive a single dose of 225Ac-PSMA-617 IA, and five participants will receive two doses over 6 weeks IV. In participants receiving two doses, the dose will be divided so that the cumulative dose will be equivalent to participants receiving a single dose. All participants will undergo prostatectomy four weeks after completing radioligand therapy and will be followed up 6 weeks after surgery for safety assessments and at 3, 6, 12, 36, 48, and 60 months for long-term outcomes.
干预措施: Prostate Tissue Collection (Procedure)
Cohort 2 (225Ac-PSMA-617)
Five participants will receive a single dose of 225Ac-PSMA-617 radioligand therapy IV, five participants will receive a single dose of 225Ac-PSMA-617 IA, and five participants will receive two doses over 6 weeks IV. In participants receiving two doses, the dose will be divided so that the cumulative dose will be equivalent to participants receiving a single dose. All participants will undergo prostatectomy four weeks after completing radioligand therapy and will be followed up 6 weeks after surgery for safety assessments and at 3, 6, 12, 36, 48, and 60 months for long-term outcomes.
干预措施: Single-photon emission computed tomography (SPECT)/Computerized tomography (CT) (Procedure)
Cohort 2 (225Ac-PSMA-617)
Five participants will receive a single dose of 225Ac-PSMA-617 radioligand therapy IV, five participants will receive a single dose of 225Ac-PSMA-617 IA, and five participants will receive two doses over 6 weeks IV. In participants receiving two doses, the dose will be divided so that the cumulative dose will be equivalent to participants receiving a single dose. All participants will undergo prostatectomy four weeks after completing radioligand therapy and will be followed up 6 weeks after surgery for safety assessments and at 3, 6, 12, 36, 48, and 60 months for long-term outcomes.
干预措施: Blood Sample Collection (Procedure)
Control Group (Prostatectomy only)
Participants will obtain a non-investigational prostatectomy. Tumor tissue obtained at the time of surgery will be utilized for comparisons with the cohorts receiving study therapies. All participants will undergo prostatectomy four weeks after completing radioligand therapy and will be followed up 6 weeks after surgery for safety assessments and up to 24 months after surgery.
干预措施: Blood Sample Collection (Procedure)
结局指标
主要结局
Mean of tumor absorbed dose (Cohorts 1 and 2)
时间窗: 1 week
The mean tumor absorbed dose on post-treatment SPECT imaging within 7 days of the first radioligand treatment (RLT) will be obtained by using MIM Software to measure absorbed dose and researchers will manually segment activity in the dominant prostate tumor while carefully excluding any activity within the bladder using a threshold of 5 Gray. Using this segmented volume, the mean dose within the tumor in Gray for each participant and standard deviation will be calculated and reported descriptively for Cohorts 1 and 2. A two-sample t-test comparing the dose between Cohort 1 and Cohort 2 and Analysis of Variance (ANOVA) model to compare the dose between different treatment/fractionation modalities within each cohort will be performed.
Rate of Cluster of differentiation 3 positive (CD3+) T cell infiltration
时间窗: 1 day, at time of prostatectomy
Immunohistochemistry will be performed using standard methods, and stained slides will be scanned using an automated microscope scanner. Five randomly selected fields (0.25 mm\^2) from each participant's primary tumor will be captured. Using color-specific algorithms, CD3+ cell counts will be determined, and the mean of each of the five quantified fields will be used. We will use a two-sample t-test or ANOVA model comparing the CD3+ cell counts between Cohort 1 and Cohort 2 with participants who have not undergone prostatectomy enrolled in the biospecimen protocol, respectively.
次要结局
- Proportion of participants with reported treatment-emergent adverse events (Cohorts 1 and 2)(Up to 6 weeks after last PSMA RLT administration)
- Proportion of participants with perioperative complications(Up to 6 weeks after prostatectomy)
- Median scores on the xerostomia-quality-of-life-scale (XeQoLS)(Up to 12 months after prostatectomy)
- Proportion of participants with 50% decrease in level of prostate specific antigen (PSA50)(Up to 8 weeks)
- Proportion of participants with complete pathologic response(1 day, at time of prostatectomy)
研究者
Thomas Hope
Professor In Residence
University of California, San Francisco