Phase I Study of 225Ac-J591 Plus 177Lu-PSMA Small Molecule for Progressive Metastatic Castration Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 42
- 试验地点
- 3
- 主要终点
- Proportion of subjects with dose limiting toxicity (DLT) of 225Ac-J591 and 177Lu-PSMA-I&T during dose-escalation phase.
研究概览
简要总结
This is a phase I dose-escalation study of 225Ac-J591 administered together with 177Lu-PSMA small molecule. Both drugs are designed to deliver radiation to prostate cancer cells; they are known as radionuclide conjugates (radiation linked to antibodies/molecules that recognize prostate cancer cells). This phase of the study (phase I) will determine the highest dose of the study intervention that can be safely given.
详细描述
This clinical trial is for men with progressive metastatic castration-resistant prostate cancer (mCRPC). The two primary objectives of this trial are to determine the highest dose of 225Ac-J591 and 177Lu-PSMA-small molecule that can be administered together (also known as maximum tolerated dose) with the recommended phase II dose and to determine the effectiveness of the drug combination. The two drugs will be co-administered every 8 weeks, for 2 cycles.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 99 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed adenocarcinoma of prostate
- •Documented progressive metastatic CRPC based on Prostate Cancer Working Group 3 (PCWG3) criteria, which includes at least one of the following criteria: PSA progression, Objective radiographic progression in soft tissue, New bone lesions
- •ECOG performance status of 0-2
- •Have serum testosterone < 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone bilateral orchiectomy
- •Have previously been treated with at least one of the following: Androgen receptor signaling inhibitor (such as enzalutamide), CYP 17 inhibitor (such as abiraterone acetate)
- •Have previously received taxane chemotherapy, been determined to be ineligible for taxane chemotherapy by their physician or refused taxane chemotherapy
- •Age > 18 years
- •Patients must have normal organ and marrow function as defined below: Absolute neutrophil count: >2,000 cells/mm3, Hemoglobin: ≥9 g/dL, Platelet count: >150,000 x 109/uL, Serum creatinine: <1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault, Serum total bilirubin: <1.5 x ULN (unless due to Gilbert's syndrome in which case direct bilirubin must be normal), Serum AST and ALT: <1.5 x ULN in the absence of liver metastases; <3 x ULN if due to liver metastases (in both circumstances bilirubin must meet entry criteria)
- •Ability to understand, and the willingness to sign, a written informed consent document
排除标准
- •Implantation of investigational medical device ≤4 weeks of Treatment visit #1 (Day 1) or current enrollment in oncologic investigational drug or device study
- •Use of investigational drugs ≤4 weeks or <5 half-lives of Treatment visit # 1(Day 1) or current enrollment in investigational oncology drug or device study
- •Prior systemic beta-emitting bone-seeking radioisotopes. Prior radium-223 is allowed provided at least 90 days have lapsed since last dose
- •For the prior PSMA-TRT-naive cohort, prior PSMA-targeted radionuclide therapy is not allowed (prior PSMA-targeted isotopes used for imaging/diagnostic purposes are allowed, as is prior PSMA-targeted therapy that does not involve therapeutic radionuclides); For the 177Lu-PSMA small molecule exposed cohort, no dose limiting toxicity may have been observed during/after therapy with prior treatment and all other entry criteria must be met
- •Known active brain or leptomeningeal metastases
- •History of deep vein thrombosis and/or pulmonary embolus within 1 month of Treatment visit #1
- •Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or hematological organ systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study
- •Radiation therapy for treatment of PC ≤4 weeks of Treatment visit #1
- •Patients on stable dose of bisphosphonates or denosumab, which have been started no less than 4 weeks prior to treatment start, may continue on this medication, however patients are not allowed to initiate bisphosphonate/Denosumab therapy during the DLT-assessment period of the study
- •Having partners of childbearing potential and not willing to use a method of birth control deemed acceptable by the principle investigator and chairperson during the study and for at least 140 days after last study drug administration
- •Currently active other malignancy other than non-melanoma skin cancer. Patients are considered not to have "currently active" malignancy if they have completed any necessary therapy and are considered by their physician to be at less than 30% risk of relapse
- •Known history of myelodysplastic syndrome
- •Bone scan with confluent lesions and lack of urinary tracer consistent with a "superscan" as determined by the investigator
- •Prior exposure to PARP inhibitor > 2 weeks
结局指标
主要结局
Proportion of subjects with dose limiting toxicity (DLT) of 225Ac-J591 and 177Lu-PSMA-I&T during dose-escalation phase.
时间窗: Will be collected at the time of visit 1 through end of study or 100 months
DLTs will be measured by utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Cumulative maximum tolerated dose (MTD) and recommended phase II dose 225Ac-J591 and 177Lu-PSMA I&T
时间窗: Will be collected at the time of visit 1 through end of study or 100 months
The dose that produces an "acceptable" level of toxicity or that, if exceeded, would put subjects at "unacceptable" risk for toxicity. Definition of the MTD usually relies on the sample, as MTD is defined as the dose level at which no more than one patient out of six experienced dose-limiting toxicity (DLT).
Proportion of PSMA+ subjects (by imaging criteria) with PSA decline following treatment with the combination of 225Ac-J591 and 177Lu-PSMA I&T.
时间窗: Will be collected at the time of visit 1 through end of study or 100 months
Proportion of patients achieving 50% or greater PSA decline (relative to baseline/pre-treatment PSA). Response may occur at any time following treatment initiation and prior to going off study or initiation of new therapy.
次要结局
- Change in circulating tumor cells (CTC) count(Samples will be collected at screening, week 12, week 24.)
- Overall survival following treatment with 225Ac-J591 and 177Lu-PSMA-I&T(Survival will be collected from Day 1 through study completion up to 100 months)
- Change in biochemical progression-free survival(Will be collected at the time of visit 1 through end of study or 100 months)
- Number of subjects with radiographic response rate(Patients will undergo imaging at screening, week 12, and week 24.)
- Safety of treatment and adverse event rate(Will be collected at the time of visit 1 through end of study or 100 months.)
- Change in disease assessment with 68Ga-PSMA-11 PET/CT prior to and following investigational treatment(Patients will undergo imaging at screening, week 12, and week 24.)