89Zr-DFO-GmAb PET/CT vs Contrast-Enhanced CT for Detection of Recurrent Clear Cell Renal Cell Carcinoma After Surgery
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 91
- 试验地点
- 1
- 主要终点
- Lesion detection rate
研究概览
简要总结
This phase II trial compares the safety and effectiveness of 89Zr-DFO-GmAb positron emission tomography (PET)/computed tomography (CT) compared to contrast-enhanced CT after surgery in detecting clear cell renal cell cancer that has come back (recurrent). For some patients, the risk of recurrence after surgery remains high. Conventional CT methods, such as contrast-enhanced CT, may not detect small volume or micrometastatic disease. PET/CT with radiotracers, such as 89Zr-DFO-GmAb, may improve detection of tumor cells. Girentuximab (GmAb), a monoclonal antibody, is tagged with zirconium-89, a radioactive atom (which is also known as an isotope). The zirconium-89 (89Zr) isotope is attached to girentuximab with desferrioxamine (DFO) and this combined product is called 89Zr-DFO-girentuximab. 89Zr-DFO-girentuximab attaches itself to a protein on the surface of clear cell renal cell tumor cells called CAIX. PET is an established imaging technique that utilizes small amounts of radioactivity attached to very minimal amounts of tracer, in the case of this research, 89Zr-DFO-GmAb. Because some cancers, including clear cell renal cell cancer, take up 89Zr-DFO-GmAb it can be seen with PET. CT utilizes x-rays that traverse body from the outside. CT images provide an exact outline of organs and potential inflammatory tissue where it occurs in patient's body. Using contrast agents with CT scan to enhance the images (contrast-enhanced CT) is standard of care imaging. 89Zr-DFO-GmAb PET/CT may be safe and effective compared to contrast-enhanced CT in detecting recurrent clear cell renal cell cancer after surgery.
详细描述
PRIMARY OBJECTIVE:
I. To compare the lesion detection rate (i.e., positivity rate per patient) of zirconium Zr 89 girentuximab (89Zr-DFO-GmAb) PET/CT compared to the standard of care diagnostic contrast-enhanced CT alone at 4-12 weeks from surgical resection based on blinded independent central review (BICR).
SECONDARY OBJECTIVES:
I. To establish safety of 89Zr-DFO-GmAb in patients with intermediate-high or high risk imaged in the post-nephrectomy or metastasectomy setting.
II. To compare the positive predictive value (PPV) of 89Zr-DFO-GmAb PET/CT in patients with available lesion validation by 1) histopathology (biopsy/resection), 2) evidence of growth under surveillance or 3) reduction of size under treatment, and 4) unequivocal confirmation of malignancy on a different imaging modality.
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
- •Histologically confirmed clear cell renal cell carcinoma (RCC) (ccRCC) (based on partial/radical nephrectomy/metastasectomy)
- •For tumors with extensive sarcomatoid features, if there is evidence of areas of clear cell and high CAIX expression throughout the tumor on immunohistochemistry, they will be allowed on study
- •Subjects must have undergone definitive treatment of their primary tumor (partial/radical nephrectomy) +/- resection of metastatic disease to no evidence of disease (NED) with a prior nephrectomy < 2 years)
- •Surgery must have been performed between 4-16 weeks at the time of planned imaging
- •Subjects are considered to have a high risk of recurrence based on the following criteria:
- •Intermediate-high risk ccRCC:
- •pathologic tumor stage 2 (pT2), grade 4, or sarcomatoid, N0, M0
- •pathologic tumor stage 3 (pT3), any grade, N0, M0
- •High risk ccRCC:
- •pathologic tumor stage 4 (pT4), any grade, N0, M0
- •pT any stage, any grade, number of positive nodes (pN+), M0
- •M1 now NED: pathologically-confirmed ccRCC, undergoing a resection of a solitary, isolated soft tissue metastasis within two years from initial nephrectomy
- •Negative serum pregnancy tests in female patients of childbearing potential. (Women of child bearing potential [WOCBP] require a negative pregnancy test within 24 hours (urine) prior to receiving investigational product)
- •Consent to practice double-barrier contraception until a minimum of 42 days after 89Zr-DFO-GmAb administration
- •Individual must be able to remain still and lie flat for duration of the diagnostic imaging procedure (less than 1 hour)
排除标准
- •Inability to provide written informed consent
- •Any evidence of residual disease or known metastasis at the time of planned 89Zr-DFO-GmAb administration
- •Prior post-operative imaging for confirmation of disease status
- •An untreated non-renal malignancy with the following exceptions:
- •Low risk prostate cancer on active surveillance (National Comprehensive Cancer Network [NCCN] very low/low risk)
- •Non-melanoma skin cancer
- •Any prior treated malignancy meeting the following characteristics:
- •Treated stage I or II cancer from which the patient is currently in complete remission
- •A stage III cancer from which the patient is progressing or has been disease-free for and has required active treatment (e.g. adjuvant or maintenance therapy) within the past 3 years prior to enrollment
- •A hematologic malignancy from which the patient is currently in complete remission
- •Contraindication to the use of iodinated contrast-enhanced CT agents, based on:
- •Severe allergy (for which pre-medication cannot limit adverse reactions) or
- •Estimated glomerular filtration rate (GFR) ≤ 30 ml/min/1.73m^2
- •Prior use of systemic therapy treatment for kidney cancer (PD-1, PD-L1, tyrosine kinase or TOR inhibitor) or radiotherapy within 4 weeks of enrollment
- •Exposure to experimental diagnostic or therapeutic drug within 14 days from date of planned administration
- •Women who are pregnant or breastfeeding
- •Known hypersensitivity to girentuximab
- •Known inability to remain still and lie flat imaging procedure (about 30 minutes)
研究组 & 干预措施
Diagnostic (89Zr-DFO-GmAb PET/CT)
Patients receive 89Zr-DFO-GmAb IV over 3 minutes on day 0 then undergo whole body PET/CT and SOC diagnostic contrast-enhanced CT scan on day 7. Patients also blood sample collection on study. In addition, patients may undergo bone scan and CT or MRI of the brain on study as clinically indicated.
干预措施: Biospecimen Collection (Procedure)
Diagnostic (89Zr-DFO-GmAb PET/CT)
Patients receive 89Zr-DFO-GmAb IV over 3 minutes on day 0 then undergo whole body PET/CT and SOC diagnostic contrast-enhanced CT scan on day 7. Patients also blood sample collection on study. In addition, patients may undergo bone scan and CT or MRI of the brain on study as clinically indicated.
干预措施: Bone Scan (Procedure)
Diagnostic (89Zr-DFO-GmAb PET/CT)
Patients receive 89Zr-DFO-GmAb IV over 3 minutes on day 0 then undergo whole body PET/CT and SOC diagnostic contrast-enhanced CT scan on day 7. Patients also blood sample collection on study. In addition, patients may undergo bone scan and CT or MRI of the brain on study as clinically indicated.
干预措施: Computed Tomography (Procedure)
Diagnostic (89Zr-DFO-GmAb PET/CT)
Patients receive 89Zr-DFO-GmAb IV over 3 minutes on day 0 then undergo whole body PET/CT and SOC diagnostic contrast-enhanced CT scan on day 7. Patients also blood sample collection on study. In addition, patients may undergo bone scan and CT or MRI of the brain on study as clinically indicated.
干预措施: Magnetic Resonance Imaging (Procedure)
Diagnostic (89Zr-DFO-GmAb PET/CT)
Patients receive 89Zr-DFO-GmAb IV over 3 minutes on day 0 then undergo whole body PET/CT and SOC diagnostic contrast-enhanced CT scan on day 7. Patients also blood sample collection on study. In addition, patients may undergo bone scan and CT or MRI of the brain on study as clinically indicated.
干预措施: Positron Emission Tomography (Procedure)
Diagnostic (89Zr-DFO-GmAb PET/CT)
Patients receive 89Zr-DFO-GmAb IV over 3 minutes on day 0 then undergo whole body PET/CT and SOC diagnostic contrast-enhanced CT scan on day 7. Patients also blood sample collection on study. In addition, patients may undergo bone scan and CT or MRI of the brain on study as clinically indicated.
干预措施: Questionnaire Administration (Other)
Diagnostic (89Zr-DFO-GmAb PET/CT)
Patients receive 89Zr-DFO-GmAb IV over 3 minutes on day 0 then undergo whole body PET/CT and SOC diagnostic contrast-enhanced CT scan on day 7. Patients also blood sample collection on study. In addition, patients may undergo bone scan and CT or MRI of the brain on study as clinically indicated.
干预措施: Zirconium Zr 89 Girentuximab (Drug)
结局指标
主要结局
Lesion detection rate
时间窗: Up to 16 weeks from surgical resection
Patients will be treated as binary categorization as follows: (i) Patients who have ≥ 1 lesion confirmed to be recurrent disease will be designated positive (recurrence). (ii) Patients with no lesions detected will be designated negative (no recurrence). The analysis of the primary objective will utilize McNemar's test to compare the detection rate between the imaging techniques.
次要结局
- Incidence of adverse events (AEs)(Up to day 14)
- Positive predictive value (PPV)(Up to 2 years)
- Recurrence-free survival(Up to 2 years)
- Change in management and perceived clinical utility of the unblinded read/report of positron emission tomography/ computed tomography (PET/CT)(At baseline and up to 2 years)