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A single-center, open-label, Phase I clinical trial to evaluate the safety, efficacy, and pharmacokinetics of 211At-NpG-PSMA radioligand therapy in patients with castration-resistant prostate cancer

Basic Information

Recruitment status	Recruiting
Health condition(s) or Problem(s) studied	Castration-Resistant Prostate Cancer
Date of first enrollment	20/10/2025
Target sample size	18
Countries of recruitment
Study type	Interventional
Intervention(s)	The investigational product will be administered as a single intravenous dose. The initial dose level will be Cohort 1 (0.39 MBq/kg). Subsequent dose escalation will proceed to Cohort 2 (0.78 MBq/kg) and Cohort 3 (1.17 MBq/kg) in accordance with the standard 3+3 dose-escalation design.

Outcome(s)

Primary Outcome

Presence or absence of dose-limiting toxicity (DLT) following a single administration of the investigational product.

Secondary Outcome

1) Safety Endpoints Adverse events 2) Efficacy Endpoints Serum PSA levels, percentage change in serum PSA, PSA response rate Quality of life assessments (EQ-5D-5L, FACT-P) Tumor shrinkage assessment at each evaluation time point: - RECIST v1.1 - Prostate Cancer Working Group 3 (PCWG3) - PCWG-modified RECIST v1.1 Best overall response (RECIST v1.1) Evaluation of bone lesions based on bone scintigraphy: - Visual assessment: Extent of Disease (EOD) - Semi-quantitative assessment: Bone Scan Index (BSI), Hot Spot (HS) 3) Radiopharmaceutical Pharmacokinetics Endpoints Blood radioactivity pharmacokinetics Urinary radioactivity pharmacokinetics

Key inclusion & exclusion criteria

Age minimum	>= 18age old
Age maximum	Not applicable
Gender	Male
Include criteria	1) Patients who are capable of providing written informed consent. 2) Patients aged 18 years or older at the time of consent. 3) Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 4) Patients histologically diagnosed with prostate cancer. Diagnosis must follow the criteria outlined in the "General Rules for Clinical and Pathological Studies on Prostate Cancer, 5th Edition." 5) Patients with positive findings on ^68Ga-PSMA-11 PET/CT scan, deemed eligible by the principal or sub-investigator. 6) Patients with serum/plasma testosterone levels below the castration threshold (<50 ng/dL or <1.7 nmol/L) within 28 days prior to enrollment. 7) Patients who have received at least one oral androgen receptor inhibitor (e.g., enzalutamide and/or abiraterone). 8) Patients with prior treatment history of one or two taxane-based chemotherapies. Taxane-based treatment is defined as having received at least two cycles of a taxane agent. If the patient has received only one taxane agent, eligibility is confirmed if: a. The treating physician determines that a second taxane agent is inappropriate due to frailty, intolerance, or patient refusal (based on geriatric or health status assessment). 9) Patients with BRCA gene mutations who are eligible for PARP inhibitors and have received prior treatment with a PARP inhibitor. 10) Patients with metastatic castration-resistant prostate cancer (mCRPC) showing disease progression, defined by at least one of the following criteria: (1) PSA progression: Defined as a >=25% increase in PSA levels from a prior reference value measured at least one week earlier, with an absolute increase of >=2 ng/mL (based on the "General Rules for Prostate Cancer, 5th Edition"). (2) Soft tissue progression: Defined as a >=20% increase in the sum of diameters (SOD) of all target lesions (short axis for lymph nodes, long axis for non-lymph nodes), or the appearance of one or more new lesions (based on RECIST v1.1 and the 5th Edition rules). (3) Bone lesion progression: Defined as the appearance of >=2 new lesions on the first post-treatment bone scan, followed by >=2 different new lesions on the subsequent scan (based on the 5th Edition rules and Prostate Cancer Clinical Trials Working Group 3 criteria). 11) Patients with at least one metastatic lesion confirmed by baseline CT, MRI, or bone scintigraphy within 28 days prior to initiation of study treatment. 12) Patients whose clinically significant toxicities related to prior therapies (chemotherapy, radiotherapy, immunotherapy, etc.) have recovered to Grade 2 or lower. 13) Patients with adequate organ function: (1) Bone marrow function: White blood cell count >=3000/uL (without G-CSF support) Hemoglobin >=9.0 g/dL (without transfusion) Platelet count >=100000/mm^3 (without transfusion) (2) Renal function: Estimated glomerular filtration rate (eGFR) >=60 mL/min/1.73m^2 (3) Hepatic function: AST <=90 U/L ALT <=126 U/L (4) Cardiac function: NYHA Functional Class I or lower (5) Respiratory status: Oxygen saturation (SpO2) >=96% on room air 14) Patients expected to survive for at least 3 months. 15) Patients who are expected to be self-sufficient in eating, excretion, and sleeping during the isolation period in the nuclear medicine therapy room.
Exclude criteria	1)Patients with active double cancers. Active double cancers are defined as synchronous or multiple cancers, and metachronous or multiple cancers with a disease-free interval of less than 5 years. However, lesions equivalent to carcinoma in situ or intramucosal carcinoma that are considered cured by local treatment and have been disease-free for more than one year are not included as active double cancers. 2)Patients who have received any of the following treatments within 6 months prior to informed consent: Strontium-89, Radium-223, PSMA-targeted radioligand therapy, Hemi-body radiation. 3)Patients who have received systemic anti-cancer therapy (e.g., chemotherapy, immunotherapy, biological therapy including monoclonal antibodies) within 28 days prior to informed consent. 4)Patients with known hypersensitivity to the investigational product or its analogs. 5)Patients receiving concurrent treatment with other cytotoxic chemotherapy, immunotherapy, or radioligand therapy. 6)Patients who received a blood transfusion solely for the purpose of meeting eligibility criteria. 7)Patients with active central nervous system (CNS) metastases. Patients with a history of CNS metastases are not excluded if they have received treatment (surgery, radiation therapy, gamma knife), are neurologically stable, asymptomatic, and are not receiving corticosteroids to maintain neurological function. Patients with a history of epidural, spinal canal, or spinal cord lesions are eligible if those lesions are treated, stable, and without neurological deficits. For patients with brain metastases (or history thereof), brain imaging (preferably MRI or contrast-enhanced CT) must be included in baseline and follow-up assessments. 8)Patients with superscan findings on baseline bone scintigraphy (diffuse bone metastases that may appear deceptively normal). 9)Patients with symptomatic spinal cord compression or clinical/radiological signs suggestive of spinal cord compression. 10)Patients who experienced Grade >=2 non-hematologic toxicities during prior treatment that cannot be ruled out as related to treatment and require medical intervention during the study period. 11)Patients with serious comorbid medical conditions (as judged by the investigator), including but not limited to: 12)Congestive heart failure classified as NYHA Class III or IV History of congenital long QT syndrome Uncontrolled infections Known active hepatitis B or C HIV infection Any other significant comorbid condition that may interfere with study participation or compliance, as determined by the investigator Patients with partners who may become pregnant and who are unwilling to use contraception for 3 months after treatment. Acceptable methods include the use of latex condoms (male), hormonal contraceptives (e.g., oral contraceptives), intrauterine devices (IUDs, T-shaped without progesterone), or a combination of at least two methods, or surgical sterilization (tubal ligation or vasectomy). Women not at risk of pregnancy are defined as those who have undergone permanent sterilization or are postmenopausal (defined as >=12 months of amenorrhea without other medical cause). 13)Patients who have received investigational drugs within the past 3 months. 14)Patients deemed inappropriate for participation in this study by the principal or sub-investigator.