Comparing DLL3 PET/CT to Standard Scans in Neuroendocrine Cancer (DSC-NEC)
A Prospective, Multi-Center, Self-Controlled Phase IIa Clinical Trial Evaluating the Diagnostic Performance and Clinical Impact of [⁶⁸Ga]Ga-DLL3 Nanobody PET/CT Compared to [¹⁸F]FDG or [⁶⁸Ga]Ga-PSMA PET/CT in Patients With Metastatic Neuroendocrine Neoplasms
This study is testing a new PET/CT scan that uses a special tracer called [⁶⁸Ga]Ga-DLL3 nanobody to see if it can better detect cancer spread (metastases) in people with neuroendocrine tumors than the standard scans currently used (FDG PET/CT or PSMA PET/CT). DLL3 is a protein found on the surface of many neuroendocrine tumor cells, and the new tracer is designed to stick to this protein, making tumors visible on the scan. The goal is to find out whether this new imaging method can give doctors more accurate information about where the cancer has spread and help them choose the most appropriate treatment for each patient.
The study is prospective, multi-center, and self-controlled, meaning each participant will receive both the new scan and the standard scan, allowing a direct side-by-side comparison in the same person. Depending on the type of neuroendocrine tumor, participants will be assigned to one of two groups: one group will be compared with FDG PET/CT and the other with PSMA PET/CT. The two scans will be performed within two weeks of each other, and all images will be read by independent experts who do not know the patient's clinical history, to ensure objective and unbiased results.
The investigators plan to enroll about 180-200 patients aged 18 or older who have confirmed neuroendocrine tumors with at least two metastatic sites. The total duration of participation is approximately 6 months, consisting of a screening period of up to 14 days, two imaging scans completed within 2 days, and a final follow-up visit at 6 months to evaluate participants' health and disease progression. Participation is entirely voluntary, and participants may withdraw at any time without affecting participants' standard medical care.
研究概览
研究类型
注册 (估计的)
阶段
- 阶段2
联系人和位置
学习联系方式
- 姓名:Tingting Yuan, MD
- 电话号码:+86 13051707479
- 邮箱:biluohtt@163.com
学习地点
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Beijing Municipality
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Beijing、Beijing Municipality、中国、100034
- Peking University First Hospital
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参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
Inclusion Criteria:
- Age ≥ 18 and ≤ 80 years at the time of signing the informed consent form, male or female.
- Histologically or cytologically confirmed neuroendocrine neoplasms (NENs), including but not limited to small cell lung cancer (SCLC), neuroendocrine prostate cancer (NEPC), gastroenteropancreatic neuroendocrine tumors (GEP-NENs), or other NEN subtypes.
- Patients with strong clinical and radiological suspicion of NENs based on imaging (CT/MRI/conventional PET/CT) and clinical presentation.
- At least 2 evaluable metastatic lesions (multiple metastases) confirmed by conventional imaging (CT/MRI/PET/CT).
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Life expectancy > 3 months.
- Voluntarily agrees to participate and provides written informed consent.
- Females of childbearing potential and male participants agree to use reliable contraceptive methods for 6 months after the last study drug administration.
- Willing and able to comply with scheduled visits, diagnostic procedures, clinical laboratory tests, and other study procedures.
Exclusion Criteria:
- Known severe immediate-type hypersensitivity or anaphylactic reaction to DLL3-targeted tracers, nanobody proteins, chelators, buffer components, or excipients.
- Pregnant or breastfeeding women.
- Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m².
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN).
- Total bilirubin > 1.5 × ULN.
- Inability to tolerate or cooperate with PET/CT imaging procedures, including but not limited to: severe claustrophobia, inability to remain supine and still for at least 30 minutes, or inability to establish adequate intravenous access.
- Received chemotherapy, biological therapy, endocrine therapy, molecular targeted therapy, or investigational drug therapy within 4 weeks prior to enrollment.
- Currently participating in another interventional clinical trial.
- Prior exposure to any DLL3-targeted therapeutic agent (e.g., Tarlatamab, bispecific T-cell engagers, or DLL3-targeted radioimmunotherapy) or DLL3-targeted radiotracer.
- Prior radionuclide therapy or diagnostic scan with an interval of less than 10 physical half-lives of the administered radionuclide prior to study tracer administration.
- History of any other malignancy within 5 years prior to screening, except for adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, or other malignancies with negligible risk of recurrence in the investigator's opinion.
- Clinically significant abnormalities on physical examination, electrocardiogram (ECG), or clinical laboratory tests during screening that, in the investigator's opinion, may compromise safety or study compliance.
- Any other condition that, in the investigator's opinion, makes the patient unsuitable for study participation (e.g., severe psychiatric disorders, substance abuse, poor compliance).
学习计划
研究是如何设计的?
设计细节
- 主要用途:诊断
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:[⁶⁸Ga]Ga-DLL3 Nanobody PET/CT
Participants receive a single intravenous injection of [⁶⁸Ga]Ga-DLL3 nanobody (a novel radiotracer targeting Delta-like ligand 3 [DLL3]), followed by whole-body PET/CT imaging at approximately 2 hours post-injection.
DLL3 is a protein aberrantly expressed on the surface of neuroendocrine tumor cells.
The nanobody is engineered for high-affinity and specificity binding to DLL3, enabling non-invasive visualization of DLL3-expressing tumor lesions.
The total injected protein mass and molar activity are controlled according to the study protocol to ensure consistent imaging quality.
PET/CT images are acquired from skull base to mid-thigh (extended to feet if clinically indicated) using a standardized acquisition protocol.
Image reconstruction is performed with consistent algorithms across all participants.
Each subject serves as their own control, with the DLL3 PET/CT results compared to their conventional imaging (FDG PET/CT or PSMA PET/CT) performed within 2 weeks.
The scan is performed
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[⁶⁸Ga]Ga-PFD3 is a novel PET tracer constructed by conjugating a DLL3-specific nanobody (single-domain antibody, ~15 kDa) with a chelator for ⁶⁸Ga radiolabeling. DLL3 (Delta-like ligand 3) is a cell-surface protein that is rarely expressed in healthy adult tissues but is overexpressed in over 80% of small cell lung cancer and in other high-grade neuroendocrine tumors, making it an attractive target for molecular imaging. The nanobody platform offers advantages over conventional monoclonal antibody-based tracers (e.g., [⁸⁹Zr]Zr-DFO-SC16.56): smaller size (~15 kDa vs. ~150 kDa) enables superior tissue penetration, rapid blood clearance, and shorter in vivo residence time, allowing same-day PET/CT imaging within hours post-injection. Participants receive a single intravenous injection of [⁶⁸Ga]Ga-PFD3 (activity: 111-185 MBq; protein mass and molar activity controlled per protocol), followed by whole-body PET/CT acquisition at approximately 2 hours post-injection. Images are acquired from
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Diagnostic Accuracy of [⁶⁸Ga]Ga-DLL3 Nanobody PET/CT in Detecting Metastatic Lesions
大体时间:Baseline (within 14 days of enrollment) and Month 6
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Sensitivity and specificity of [⁶⁸Ga]Ga-DLL3 nanobody PET/CT for detecting metastatic lesions in patients with neuroendocrine neoplasms, using a composite reference standard (incorporating histopathology, conventional imaging [FDG/PSMA PET/CT, diagnostic CT/MRI], and 6-month clinical/imaging follow-up) as the truth standard.
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Baseline (within 14 days of enrollment) and Month 6
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Lesion Detection Rate
大体时间:Baseline (within 14 days of enrollment)
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Per-lesion detection rate of [⁶⁸Ga]Ga-DLL3 PET/CT compared to FDG or PSMA PET/CT, stratified by anatomical location (e.g., liver, bone, lung, brain, lymph nodes).
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Baseline (within 14 days of enrollment)
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Clinical Management Change Rate
大体时间:Baseline (at time of image interpretation, within 14 days of enrollment)
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Proportion of patients whose clinical management (e.g., staging, treatment selection, or biopsy site decision) is altered based on [⁶⁸Ga]Ga-DLL3 PET/CT results compared to conventional imaging.
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Baseline (at time of image interpretation, within 14 days of enrollment)
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Safety and Tolerability
大体时间:Up to 24 hours post-injection
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Incidence, severity, and causality of adverse events (graded per CTCAE v5.0) following single intravenous injection of [⁶⁸Ga]Ga-DLL3 nanobody, including injection site reactions, allergic reactions, and any serious adverse events.
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Up to 24 hours post-injection
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Correlation with DLL3 Expression
大体时间:At study completion (expected at Month 6)
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Correlation between [⁶⁸Ga]Ga-DLL3 PET/CT uptake (SUVmax, SUVmean) and DLL3 expression level by immunohistochemistry (IHC) in biopsied tumor specimens (where available).
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At study completion (expected at Month 6)
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Target-to-Background Ratio (TBR)
大体时间:Baseline (within 14 days of enrollment)
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Quantitative comparison of TBR between [⁶⁸Ga]Ga-DLL3 PET/CT and standard scans (FDG or PSMA PET/CT) in identified lesions, with background regions pre-defined as liver, blood pool, and muscle.
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Baseline (within 14 days of enrollment)
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其他结果措施
结果测量 |
措施说明 |
大体时间 |
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Baseline SUVmax of [⁶⁸Ga]Ga-DLL3 PET/CT as a Predictor of Clinical Benefit
大体时间:Baseline (within 14 days of enrollment)
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The maximum standardized uptake value (SUVmax) derived from baseline [⁶⁸Ga]Ga-DLL3 nanobody PET/CT imaging, measured within 14 days prior to enrollment.
The optimal cut-off value for SUVmax will be determined using receiver operating characteristic (ROC) curve analysis to stratify patients into high- vs. low-expression groups.
This individual parameter will be evaluated for its ability to predict objective response or progression-free survival benefit from DLL3-targeted therapies (e.g., Tarlatamab).
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Baseline (within 14 days of enrollment)
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Hazard Ratio (HR) for 24-Month Overall Survival Based on Baseline SUVmax Cut-off
大体时间:Baseline (within 14 days of enrollment) and Month 24
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The hazard ratio (HR) with 95% confidence interval, derived from univariate Cox proportional hazards regression, comparing 24-month overall survival between neuroendocrine neoplasm patients stratified by the optimal baseline [⁶⁸Ga]Ga-DLL3 nanobody PET/CT SUVmax cut-off value (high-expression vs. low-expression groups).
Overall survival is measured as time (in months) from enrollment to death from any cause.
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Baseline (within 14 days of enrollment) and Month 24
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合作者和调查者
出版物和有用的链接
一般刊物
- Henke RM, Meredith DM, Borromeo MD, Savage TK, Johnson JE. Ascl1 and Neurog2 form novel complexes and regulate Delta-like3 (Dll3) expression in the neural tube. Dev Biol. 2009 Apr 15;328(2):529-40. doi: 10.1016/j.ydbio.2009.01.007. Epub 2009 Jan 14.
- Tendler S, Dunphy MP, Agee M, O'Donoghue J, Aly RG, Choudhury NJ, Kesner A, Kirov A, Mauguen A, Baine MK, Schoder H, Weber WA, Rekhtman N, Lyashchenko SK, Bodei L, Morris MJ, Lewis JS, Rudin CM, Poirier JT. Imaging with [89Zr]Zr-DFO-SC16.56 anti-DLL3 antibody in patients with high-grade neuroendocrine tumours of the lung and prostate: a phase 1/2, first-in-human trial. Lancet Oncol. 2024 Aug;25(8):1015-1024. doi: 10.1016/S1470-2045(24)00249-3. Epub 2024 Jun 28.
- Lahiri A, Maji A, Potdar PD, Singh N, Parikh P, Bisht B, Mukherjee A, Paul MK. Lung cancer immunotherapy: progress, pitfalls, and promises. Mol Cancer. 2023 Feb 21;22(1):40. doi: 10.1186/s12943-023-01740-y.
研究记录日期
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学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他研究编号
- NEC-DLL3-01
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IPD 计划说明
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