A Confirmatory, Open-label, Single-arm, Multi-centre Study to Evaluate Safety, Tolerability and Diagnostic Performance of 89Zirconium-labelled Girentuximab (89Zr-TLX250) to Non-invasively Detect Clear Cell Renal Cell Carcinoma (ccRCC) by Positron Emission Tomography/Computed Tomography (PET/CT) Imaging in Chinese Patients With Indeterminate Renal Masses (ZIRCON-CP Study)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 82
- 试验地点
- 8
- 主要终点
- To evaluate the sensitivity and specificity of qualitative assessment of PET/CT imaging with 89Zr-TLX250 to non-invasively detect ccRCC in patients with indeterminate renal masses, using histology as standard of truth
研究概览
简要总结
89Zr-TLX250 is under clinical development as a diagnostic agent targeting clear cell renal cell carcinoma, and this Phase 3 bridging study in mainland Chinese patients is intended to support the successful ZIRCON data (ZIRCON Clinicaltrial.gov ID: NCT03849118)
详细描述
This will be a confirmatory, prospective, open-label, single-arm, multi-centre study in a Chinese patient population. The study is designed to evaluate the safety, tolerability, sensitivity and specificity of 89Zr-TLX250 Positron Emission Tomography/Computed Tomography (PET/CT) imaging to non-invasively detect Clear Cell Renal Cell Carcinoma (ccRCC). The multi-centre study will be conducted in mainland China in adult patients with Indeterminate Renal Masses (IRM), who are scheduled for partial or total nephrectomy as part of their standard of care.
Approximately 82 evaluable adult patients will be recruited from approximately 8 renal cancer care specialist centres with access to state-of-the-art PET/CT imaging in mainland China. The number of enrolled participants may be increased to ensure sufficient confidence in measuring sensitivity and specificity of 89Zr-TLX250 PET/CT imaging.
The study involves a single administration of 37 MBq (±10%) of 89Zr-TLX250, containing a mass dose of 10 mg of girentuximab, in mainland Chinese participants (ZIRCON-CP). This is consistent with the confirmatory, prospective, multinational clinical trial ZIRCON (ClinicalTrials.gov ID: NCT03849118). This study consists of seven visits. Imaging will then be conducted 5±2 days post administration. The partial/total nephrectomy will then be performed at institutional discretion any time following the PET/CT imaging visit, but no later than 90 days post administration of 89Zr-TLX250. Histological tumour samples will be prepared and used for histological diagnosis of the renal mass (ccRCC or non-ccRCC) read by a central laboratory.
On Day 5±2 post study drug administration, an abdominal PET/CT imaging will be obtained. In patients, in which unexpected evidence for disseminated disease is observed, PET/CT imaging may be extended to complete whole body imaging(vertex of skull to toe) at the discretion of the investigator.
Image data analyses will be performed by a central imaging vendor.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written and voluntarily given informed consent.
- •Mainland Chinese male or female, aged ≥ 18 years.
- •Imaging evidence of a single IRM of ≤ 7 cm in largest diameter (tumour stage cT1), on SoC imaging based on national standards, not older than 90 days on Day 0, but performed before any screening procedure.
- •Scheduled for lesion resection as part of regular diagnostic work-up within 90 days from planned IV 89Zr-TLX250 administration.
- •Negative serum pregnancy tests in female patients of childbearing potential at screening. Confirmation of negative pregnancy test result from urine within 24 hours prior to receiving investigational product.
- •Sufficient life expectancy to justify nephrectomy.
- •Consent to practise highly effective contraception until a minimum of 42 days after IV 89Zr-TLX250 administration.
排除标准
- •A biopsy procedure only (rather than partial or total nephrectomy) is planned for histological species delineation of IRM.
- •Renal mass known to be a metastasis of another primary tumour.
- •Active non-renal malignancy requiring therapy during the time frame of the study participation.
- •Multiple unilateral or bilateral IRM.
- •Chemotherapy, radiotherapy, targeted therapy or immunotherapy within 4 weeks prior to the planned administration of 89Zr -TLX250 or continuing adverse effects (> grade 1) from such therapy (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0).
- •Planned antineoplastic therapies (for the period between IV administration of 89Zr-TLX250 and imaging).
- •Exposure to murine or chimeric antibodies within the last 5 years.
- •Previous administration of any radionuclide within 10 half-lives of the same.
- •Serious non-malignant disease (e.g. psychiatric, infectious, autoimmune or metabolic), that may interfere with the objectives of the study or with the safety or compliance of the study subject, as judged by the investigator.
- •Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
- •Exposure to any experimental diagnostic or therapeutic drug within 4 weeks or 5 half-lives (whichever is longer) from the date of planned administration of 89Zr-TLX
- •Women who are pregnant or breastfeeding.
- •Known hypersensitivity to girentuximab or desferoxamine (DFO).
- •Renal insufficiency with glomerular filtration rate (GFR) ≤ 45 mL/min/1.73 m².
- •Vulnerable patients (e.g., being in detention).
研究组 & 干预措施
Experimental arm receiving the IP
Approximately 82 evaluable adult patients will be recruited from approximately 8 renal cancer care specialist centres with access to state-of-the-art PET/CT imaging in mainland China. The number of enrolled participants may be increased to ensure sufficient confidence in measuring sensitivity and specificity of 89Zr-TLX250 PET/CT imaging.
Following pre-screen morphological imaging to confirm evidence of IRM (to occur within 90 days of study enrolment), participants will attend a screening visit within 30 days of study enrolment, at which time baseline examinations will be undertaken.
On Day 0, all successfully screened participants will undergo a slow IV administration of 89Zr- TLX250, at the nuclear medicine service of the respective study site. For all subjects, a PET/CT scan of the abdomen will occur on visit Day 5 (±2 days post administration [p.a.]) with nephrectomy to be performed any time after the PET/CT imaging visit, but no later than 90 days p.a. 89Zr-TLX250.
干预措施: 89Zr-TLX250 PET/CT (Drug)
结局指标
主要结局
To evaluate the sensitivity and specificity of qualitative assessment of PET/CT imaging with 89Zr-TLX250 to non-invasively detect ccRCC in patients with indeterminate renal masses, using histology as standard of truth
时间窗: From Visit 4 till end of study. Diagnostic PET/CT scan on Day 5±2 days post 89Zr-TLX250 administration. Histological confirmation of the material from nephrectomy conducted within 90 days post 89Zr-TLX250 administration served as standard of truth
Evaluating this outcome involved using a PET/CT machine on all patients to determine the uptake of the Zr89 radiotracer within the renal lesion, which was then compared to the histological determination of the lesion type following resection
次要结局
- To determine the 89Zr-TLX250's test performance(Day of Imaging (Day 5±2 post- IP administration), Post-Imaging study visit (Day 42±7 post- IP administration), Day of surgery (within 28 days post-IP administration) or Day of surgery (28 to 90 days post-IP administration).)
- To assess the safety and tolerability of 89Zr-TLX250(Day of IP administration (Day 0), Day of Imaging (Day 5±2 post- IP administration), Post-Imaging study visit (Day 42±7 post- IP administration), Day of surgery (within 28 days post-IP administration) or Day of surgery (28-90 days post-IP administration))
- To evaluate the impact of 89Zr-TLX250 PET/CT on clinical decision-making as a diagnostic tool(Day of Imaging (Day 5±2 post- IP administration), Post-Imaging study visit (Day 42±7 post- IP administration), Day of surgery (within 28 days post-IP administration) or Day of surgery (28 to 90 days post-IP administration).)