A Phase I Study of [18F]DASA-23 as a PET Tracer for Evaluating Pyruvate Kinase M2 (PKM2) Expression in Healthy Volunteers and in Patients With Intracranial Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Change in [18F]DASA-23 PET scan signal in patients with suspected recurrent glioblastoma
研究概览
简要总结
This phase I trial studies how well [18F]DASA-23 and positron emission tomography (PET) scan work in evaluating pyruvate kinase M2 (PKM2) expression in patients with intracranial tumors or recurrent glioblastoma and healthy volunteers. PKM2 regulates brain tumor metabolism, a key factor in glioblastoma growth. [18F]DASA-23 is a radioactive substance with the ability to monitor PKM2 activity. A PET scan is a procedure in which a small amount of a radioactive substance, such as [18F]DASA-23, is injected into a vein, and a scanner is used to make detailed, computerized pictures of areas inside the body where the substance is used. Tumor cells usually pick up more of these radioactive substances, allowing them to be found. Giving [18F]DASA-23 with a PET scan may help doctors evaluate PKM2 expression in healthy volunteers and in participants with intracranial tumors or recurrent glioblastoma.
详细描述
PRIMARY OBJECTIVES:
I. Determine whether the fluorine F 18 DASA-23 ([18F]DASA 23) PET scan signal change from pre-therapy to one week after initiation of therapy can predict the tumor's responsiveness to therapy and 6 month progression free survival (PFS6), in suspected recurrent glioblastoma.
SECONDARY OBJECTIVES:
I. Determine the sensitivity, specificity, and accuracy of [18F]DASA-23 PET imaging in identifying intracranial tumors in patients with intracranial tumors.
II. Determine whether the [18F]DASA-23 PET scan signal change from pre therapy to one week after initiation of therapy can predict progression free survival (PFS) and overall survival (OS), in suspected recurrent glioblastoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- 是
入选标准
- •Age ≥18 years old.
- •Adequate organ function (obtained within 14 days prior to PET scan [Part 1, Part 2, and Part 3 ONLY] or within 28 days prior to PET scan [Part 4 ONLY]) as evidenced by:
- •ANC ≥ 1.5 X 10^9/L w/o myeloid growth factor support for 7 d preceding lab assessment
- •Hgb ≥ 9 g/dL (90 g/L); < 9 g/dL (< 90 g/L) is acceptable if Hgb is corrected to ≥ 9 g/dL (90 g/L) as by growth factor or transfusion prior to PET scan
- •Platelet count ≥ 100 X 10^9/L w/o blood transfusions for 7 d preceding lab assessment
- •Bilirubin ≤ 1.5 X ULN except for pts w/ documented history of Gilbert's disease
- •ALT and AST ≤ 2.5 X ULN
- •Alkaline phosphatase (AP) ≤ 3 X ULN
- •Women of childbearing potential (WCBP): negative serum pregnancy test
- •Ability to stand up and climb two steps with minimal assistance.
- •Ability to understand and the willingness to sign a written informed consent document.
- •(Part 2, intracranial tumor patients ONLY) (a) Radiographical or pathological evidence of newly-diagnosed intracranial tumor that is status-pre surgical resection, or (b) Radiographical or pathological evidence of progressive/recurrent intracranial tumor, (c) Question of pseudoprogression vs. true progression on most recent standard-of-care brain MRI, or (d) Evidence on the most recent standard-of-care brain MRI scan of intracranial metastasis/metastases in a patient with known extracranial primary cancer.
- •(Part 3, GBM patients ONLY) Any patient with at least a 1cm3 contrast-enhancing lesion suspicious for GBM (either newly-diagnosed or 1st /2nd/ 3rd recurrence of GBM, molecular GBM, diffuse astrocytomas with molecular features of GBM, H3K27M midline gliomas, gliosarcomas, or any other WHO Grade IV glioma) on a standard-of-care (SOC) brain MRI scan. If the patient undergoes a biopsy or resection for GBM (either newly-diagnosed or 1st /2nd/ 3rd recurrence of GBM, molecular GBM, diffuse astrocytomas with molecular features of GBM, H3K27M midline gliomas, gliosarcomas, or any other WHO Grade IV glioma) then the remaining contrast-enhancing lesion is at least 1cm3 in size on the post-operative scan.
- •(Part 3, GBM patients ONLY) Life expectancy of ≥ 6 months.
排除标准
- •Known allergy to adhesive tapes or other skin adhesives used in medical care
- •Subjects with the following co-morbid disease or incurrent illness:
- •With known cirrhosis diagnosed with Child-Pugh Class A or higher liver disease.
- •Severe/uncontrolled inter-current illness within the previous 28 days prior to PET scan
- •Patients who have implantable devices that are contra-indicated for MRI
- •Bleeding disorder
- •Any other significant co-morbid conditions that in the opinion of the Investigator would impair study participation or cooperation.
- •(Healthy volunteers ONLY - Part 1 and Part 4) prior or current malignancy
- •(Healthy volunteers ONLY - Part 1 and Part 4) known kidney disease
- •Pregnant or nursing participants
- •History of allergic reactions to gadolinium-based MRI contrast agent
- •(Part 2, intracranial tumor patients ONLY) Other chemotherapy (besides what is being used to treat the intracranial tumor)
- •(Part 3, GBM patients ONLY) Has already begun therapy, prior to the first of two [18F]DASA-23 PET/MRI scans.
研究组 & 干预措施
Group I ([18F]DASA-23, PET)
Healthy volunteers receive [18F]DASA-23 IV and undergo brain PET scan over 15 minutes and 4 vertex-to-toe PET scans over 30 minutes each.
干预措施: Fluorine F 18 DASA-23 (Drug)
Group I ([18F]DASA-23, PET)
Healthy volunteers receive [18F]DASA-23 IV and undergo brain PET scan over 15 minutes and 4 vertex-to-toe PET scans over 30 minutes each.
干预措施: Positron Emission Tomography (Procedure)
Group II ([18F]DASA-23, PET)
Intracranial tumor participants receive [18F]DASA-23 IV and undergo brain PET scan over 60 minutes and 1 vertex-to-toe PET scan over 30 minutes.
干预措施: Fluorine F 18 DASA-23 (Drug)
Group II ([18F]DASA-23, PET)
Intracranial tumor participants receive [18F]DASA-23 IV and undergo brain PET scan over 60 minutes and 1 vertex-to-toe PET scan over 30 minutes.
干预措施: Positron Emission Tomography (Procedure)
Group III ([18F]DASA-23, PET)
Patients with at least a 1cm3 contrast-enhancing lesion suspicious for GBM (either newly-diagnosed or 1st /2nd/ 3rd recurrence of GBM) on a standard-of-care (SOC) brain MRI scan. If the patient undergoes a biopsy or resection for GBM (either newly-diagnosed or 1st /2nd/ 3rd recurrence of GBM) then the remaining contrast-enhancing lesion is at least 1cm3 in size on the post-operative scan. These patients will undergo one [18F]DASA 23 PET/MRI scan before the initiation of therapy, and a second/final [18F]DASA 23 PET/MRI scan within 2-6 weeks after initiation of therapy for their GBM.
干预措施: Fluorine F 18 DASA-23 (Drug)
Group III ([18F]DASA-23, PET)
Patients with at least a 1cm3 contrast-enhancing lesion suspicious for GBM (either newly-diagnosed or 1st /2nd/ 3rd recurrence of GBM) on a standard-of-care (SOC) brain MRI scan. If the patient undergoes a biopsy or resection for GBM (either newly-diagnosed or 1st /2nd/ 3rd recurrence of GBM) then the remaining contrast-enhancing lesion is at least 1cm3 in size on the post-operative scan. These patients will undergo one [18F]DASA 23 PET/MRI scan before the initiation of therapy, and a second/final [18F]DASA 23 PET/MRI scan within 2-6 weeks after initiation of therapy for their GBM.
干预措施: Positron Emission Tomography (Procedure)
Group IV ([18F]DASA-23, PET)
Healthy volunteers receive [18F]DASA-23 IV and undergo brain PET/MRI brain scan for 60 mins
干预措施: Fluorine F 18 DASA-23 (Drug)
Group IV ([18F]DASA-23, PET)
Healthy volunteers receive [18F]DASA-23 IV and undergo brain PET/MRI brain scan for 60 mins
干预措施: Positron Emission Tomography (Procedure)
结局指标
主要结局
Change in [18F]DASA-23 PET scan signal in patients with suspected recurrent glioblastoma
时间窗: From pre-treatment to one week after initiation of treatment
Response to treatment is based on the response assessment in neuro-oncology (RANO) criteria. Each patient will be dichotomized into responding (yes) or not responding (no) to treatment based on RANO criteria. The \[18F\]DASA-23 PET scan signal will be calculated according to the European Organization for Research and Treatment of Cancer (EORTC) response criteria guidelines and reported as median and range, both for the entire cohort as well as separately for the responder and non-responder subgroups. The Mann-Whitney test of \[18F\]DASA-23 PET scan signal between responders and non-responders will be performed.
次要结局
- Overall survival in patients with suspected recurrent glioblastoma(From time of initial diagnosis up to 2 years)
- Sensitivity of [18F]DASA-23 PET imaging in identifying intracranial tumors in patients with intracranial tumors.(Time of the [18F]DASA-23 PET scan)
- Specificity of [18F]DASA-23 PET imaging in identifying intracranial tumors in patients with intracranial tumors.(Time of the [18F]DASA-23 PET scan)
- Accuracy of [18F]DASA-23 PET imaging in identifying intracranial tumors in patients with intracranial tumors.(Time of the [18F]DASA-23 PET scan)
- Progression-free survival in patients with suspected recurrent glioblastoma(Time from diagnosis up to 1 year)
研究者
Guido A. Davidzon, MD, SM
Clinical Associate Professor
Stanford University