An Open-label, Phase I Study to Assess Safety, Tolerability, Radiation Dosimetry, and Imaging Properties of 89Zr-labelled Girentuximab (89Zr-girentuximab) for in Vivo Detection of Clear Cell Renal Carcinoma (CCRC) by Positron Emission Tomography (PET) Using Different PET Imaging Methodologies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Safety parameter Vital Signs
研究概览
简要总结
The study is designed to explore the safety and tolerability as well as diagnostic 89Zr-girentuximab for imaging CCRC by PET/CT. This study does not offer any treatment for patients with CCRC; therefore, patients will be offered state of the art therapeutic options after imaging with the study drug 89Zr-girentuximab. Cancer treatment will not be delayed by study participation.
详细描述
The identification of RCC is crucial for planning possible surgery and treatment. The aim of this study is to investigate the safety, tolerability, radiation dosimetry, as well as the diagnostic performance of 89Zr-girentuximab PET/CT in patients with suspected CCRC. The results of this study will be used to pave the way for further studies with 89Zr-girentuximab as a PET/CT imaging agent which was shown to have higher diagnostic resolution 124I-girentuximab in animal studies due to prolonged trapping of the radiolabel in the tumour and simultaneous washout from normal tissues. It is anticipated to develop 89Zr-girentuximab as an improved imaging agent for CCRC.
This will be an exploratory, open-label, Phase 1 study to evaluate safety, tolerability, whole body dosimetry, and imaging properties of 89Zr-girentuximab, when image acquisition is made using different PET reconstruction methods, namely time-of-flight (TOF-PET) and conventional (PET) reconstruction, in order to estimate a possible impact of variable scanner technology on image quality variability in a planned multi-centre study.
In addition, different acquisition durations (5 -20 min) will be explored using an activity dose of 37 mBq (1 mCi), in order to establish, whether acquisition time has an impact on diagnostic performance.
It is anticipated to recruit 8-10 patients with suspected or established CCRC to
- Receive a slow intravenous injection with 89Zr-girentuximab (1-2 minutes slow bolus injection), followed by
- Dosimetric and tumour PET/CT imaging. The study duration will be approximately 12 months. Primary endpoint is safety, a part of which is determining the effective dose (mSv/MBq) to the whole body, and absorbed dose (mGy/MBq) to individually discernible organs.
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
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Male or female >50 years of age
- •Clinical suspicion of CCRC, based on imaging evidence of a renal mass, requiring further diagnostic work-up or patients with established diagnosis of CCRC requiring imaging for recurrent disease
- •Life expectancy of at least 6 months
- •Consent to practise double-barrier contraception until end of study (7 days after 89Zr-girentuximab injection)
排除标准
- •Known hypersensitivity to girentuximab
- •Known uncontrolled hyperthyreoidism
- •Exposure to any experimental diagnostic or therapeutic drug within 30 days from the date of planned administration of 89Zr-girentuximab
- •Exposure to any radiopharmaceutical within 30 days (corresponding to 8 half-lives of 89Zr) prior to the administration of 89Zr-girentuximab.
- •Ongoing toxicity grade 2 from previous standard or investigational therapies (Common Terminology Criteria for Adverse Events [CTCAE] version 4.03)
- •Planned (for the period between injection of 89Zr-girentuximab and imaging) antineoplastic therapies
- •Established renal cell carcinomas of other histological entities than CCRC
- •Known brain metastases
- •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 patient, as judged by the investigator
- •Pregnant or breast-feeding women. Female patients of childbearing potential or male patients with female partners of childbearing potential, unless willing to practice full and true sexual abstinence or being surgically/permanently sterile or with a history of hysterectomy for women, not willing to practice effective double-barrier contraception by using: a non-oral, injected or implanted non-oestrogen progesterone based hormonal method, male condom, vaginal diaphragm, cervical cap, intrauterine device, during the study period and within a period of 30 days (corresponding to 8 half-lives of 89Zr) after receiving study drug.
- •Patients not able to declare meaningful informed consent on their own (e.g. with legal guardian for mental disorders)
研究组 & 干预措施
89Zr-girentuximab
A single administration of 37 MBq (+/-10%) 89Zr-girentuximab, containing a mass dose of 5 mg of girentuximab
干预措施: 89Zr-Girentuximab (Diagnostic Test)
结局指标
主要结局
Safety parameter Vital Signs
时间窗: 8 days
Frequency of occurrence and severity of abnormal findings in safety investigations regarding the Vital signs including the 12-lead ECG.
Safety parameter Adverse Events
时间窗: 8 days
Frequency of occurrence and severity of abnormal findings in safety investigations regarding Adverse Events.
Safety parameter Laboratory examinations
时间窗: 8 days
Frequency of occurrence and severity of abnormal findings in safety investigations regarding Laboratory examinations.
Safety parameter concomitant medications
时间窗: 8 days
Frequency of occurrence and severity of abnormal findings in safety investigations regarding concomitant medications.
Safety parameter Physical Examination
时间窗: 8 days
Frequency of occurrence and severity of abnormal findings in safety investigations regarding the physical examination.
次要结局
- Tumour dosimetry absorbed Dose(PET/CT, Days 3 (72 h) and 7(168 h)±1 post-infusion, with the contrast enhanced anatomical CT acquired as part of the baseline scan.)
- Diagnostic efficacy(PET image acquisitions will be obtained in list mode on a TOF-capable machine for a period of 20 minutes.)
- Radiation dosimetry(Whole body (neck to mid-thigh) static PET/CT scans will be acquired in supine position at 0.5, 4, 24, 72 and 168±24 h (Day 7±1) post injection, using low dose CT without contrast agent.)
- Tumour dosimetry Absorbed dose(PET/CT, Days 3 (72 h) and 7(168 h)±1 post-infusion, with the contrast enhanced anatomical CT acquired as part of the baseline scan.)
- Tumour dosimetry Activity(PET/CT, Days 3 (72 h) and 7(168 h)±1 post-infusion, with the contrast enhanced anatomical CT acquired as part of the baseline scan.)