Open-label Phase I of 89Zr-girentuximab (89Zr-TLX250) to Assess the Safety, Biodistribution, Pharmacokinetics and Sensitivity/Specificity of PET/CT Images in Patients With Suspected Renal Cell Carcinoma Including Clear Cell Renal Cell Carcinoma (ZIRDAC-JP Study)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- Determination of the sensitivity and specificity of 89Zr-TLX250 to detect clear cell renal cell carcinoma
研究概览
简要总结
89Zr-TLX250 is a carbonic anydrase IX (CAIX)-targeted imaging agent that is under clinical development as a non-invasive diagnostic imaging agent for teh detection of clear cell renal cell carcinoma (ccRCC). The Phase 1 study part of this study is to confirm the safety/tolerability and to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) in subjects with suspected renal cell carcinoma (RCC) including clear cell renal cell carcinoma. The Phase 2 component of the study is to to evaluate the sensitivity/specificity of using 89Zr-TLX250 PET/CT images to detect RCC and ccRCC in patients with suspected RCC.
详细描述
Phase 1:
The phase 1 component of this study will be conducted in in 6-10 subjects at one study center, with the objective of confirming the safety/tolerability and the whole-body dose distribution of 89Zr-TLX250. 89Zr-TLX250 will be administered via a single IV injection (at least 3 min) at an activity dose of 37 MBq (± 10%) and at a dose of 10 mg (±10%). After the enrollment of 6 subjects, if the male-to-female ratio is different from the Japanese epidemiological RCC data (male-to-female ratio ≒ 2:1 in 2017), more subjects, up to 10 subjects in total, are to be enrolled.
Blood sampling for pharmacokinetic analysis will be is performed at 0.5, 1, 2, 4, 24, 72 h and during the Day 5 ± 2 imaging visit. The dose distribution will be determined using low-dose, non-contrast-enhanced CT whole body imaging at 0.5, 4, 24, 72 h and Day 5 ± 2. Diagnostic images will be acquired on Day 3 and Day 5 ± 2 using whole body PET/CT-imaging where individual organs will be assessed using Medical Internal Radiation Dose (MIRD) method.
Seven days after the Day 5 ± 2 imaging visit, patients will attend a follow-up visit to conduct safety evaluations and to undergo blood sampling for HACA measurement.
Phase 2:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Health Services Research
- 盲法
- None
入排标准
- 年龄范围
- 20 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
- •Aged ≥20 years at the time of enrollment
- •Suspected renal cell carcinoma who have been diagnosed with a renal mass by CT or MRI performed within 90 days before screening
- •Sufficient life expectancy to participate in the study
- •Consent to practice barrier contraception (condoms) until a minimum of 42 days and 90 days after 89Zr-TLX250 administration in female and male, respectively
- •Phase 2 Part
- •Written and voluntarily given informed consent
- •Aged ≥20 years at the time of enrollment
- •Imaging evidence of a single indeterminate renal mass of ≤ 7 cm in largest diameter on CT or MRI within 90 days prior to screening
- •Scheduled for lesion resection as part of regular diagnostic work-up within 90 days from planned 89Zr-TLX250 administration
- •Sufficient life expectancy to undergo nephrectomy
- •Consent to practice barrier contraception (condoms) until a minimum of 42 days and 90 days after 89Zr-TLX250 administration in female and male, respectively
排除标准
- •Commonly applied for Phase 1 part and Phase 2 part
- •Those who have hypersensitivity to Girentuximab or DFO
- •Patients with metastatic renal tumor
- •Patients who need treatment for other active malignancies during the study period
- •Patients who have undergone chemotherapy, radiation therapy, or immunotherapy within 4 weeks before the administration of the investigational drug, or have continued adverse events of grade 1 (defined in NCI-CTCAE v5.0) or higher
- •Patients scheduled for anticancer drug treatment during the period from administration of investigational drug to image collection
- •Patients who have been exposed to mouse or chimeric antibody within the past 5 years
- •Patients who have been administered some kind of radionuclide earlier than 10 half-lives of the nuclide.
- •Patients with severe, but not fatal disease, for which the principal investigator / investigator has determined that study participation is not appropriate
- •Women who are pregnant or breastfeeding. And women with childbearing potential who are not pregnant or breastfeeding but suspected of being pregnant by the blood test at screening and pre-dose (within 24 hours before administration). Pre-dose blood pregnancy test can be replaced with urine test
- •Patients who have been administered the drug by any clinical study or clinical trial within 30 days before the scheduled administration of the investigational drug
- •Patients who cannot give legally valid consent by himself / herself
- •Patients with renal dysfunction whose GFR is 60mL / min / 1.73m2 or less
- •Patents who are socially vulnerable (e.g., patients in custody)
- •Others who are judged by the principal investigator or investigator to be inappropriate for participation in this trial Applied only to Phase 2 part 15． Patients whose biopsy is more suitable for pathological diagnosis than partial resection or nephrectomy
结局指标
主要结局
Determination of the sensitivity and specificity of 89Zr-TLX250 to detect clear cell renal cell carcinoma
时间窗: 90 days
The sensitivity and specificity of 89Zr-TLX250 to detect renal cell carcinoma will be established by a diagnostic scan after administration of the investigational product followed by surgery of the indeterminate mass. After surgical removal of the kidney mass , diagnostic histology of the mass will be conducted and used as the "standard of truth" comparator.
Incidence of Treatment-Emergent Adverse events [Safety and Tolerability]
时间窗: 90 days
Incidence of abnormal laboratory test results and abnormal vital signs
次要结局
- Phase 2: To evaluate negative predictive value (NPV) of 89Zr-girentuximab PET/CT imaging to detect ccRCC in patients with indeterminate solid renal masses(At end of study , on average of 5 months)
- To evaluate accuracy of 89Zr-girentuximab PET/CT imaging to detect ccRCC in patients with indeterminate solid renal masses(At end of study , on average of 5 months)
- Phase 1: Evaluation of the radioactivity distribution and biodistribution/tumor uptake(0.5, 4, 24, and 72 hours and Day 5 ± 2)
- Phase 2: To evaluate positive predictive value (PPV) of 89Zr-girentuximab PET/CT imaging to detect ccRCC in patients with indeterminate solid renal masses(At end of study , on average of 5 months)
- Phase 1: Assessment of tumor uptake(Day 3-5)
- Phase 2: To evaluate the correlation between 89Zr- girentuximab SUVs and degree of histological carbonic anhydrase IX (CAIX) expression(Within 90 days)
- Phase 2: To evaluate inter-reader variability of diagnostic assessments of 89Zr- girentuximab PET/CT images, when performed by multiple readers(This analysis will be conducted through study completion, on average of 5 months)
- Phase 2: Assessment of differences in a same reader(This analysis will be conducted through study completion, on average of 5 months)