[18F]DASA-23 and PET Scan in Evaluating Pyruvate Kinase M2 Expression in Patients With Intracranial Tumors or Recurrent Glioblastoma and Healthy Volunteers

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

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.

Study Overview

• Status: Terminated
• Conditions: Glioblastoma; Healthy Subject; Intracranial Neoplasm
• Intervention / Treatment: Procedure: Positron Emission Tomography; Drug: Fluorine F 18 DASA-23

Detailed Description

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.

OUTLINE: Participants are assigned to 1 of 4 groups.

GROUP I: Healthy volunteers receive [18F]DASA-23 intravenously (IV) and undergo brain PET scan over 15 minutes and 4 vertex-to-toe PET scans over 30 minutes each.

GROUP II: 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.

GROUP III: Subjects with glioblastoma will receive [18F]DASA-23 IV and undergo brain PET scan over 60 minutes and 1 vertex-to-toe PET scan over 30 minutes. 15-minute vertex-to-thigh PET for Part 3 patients, Participants undergo second PET scan 7 days after the initiation of therapy.

GROUP IV: Healthy volunteers will undergo the same procedures as the healthy volunteers in Group I with the following exceptions:

Group IV healthy volunteers will undergo a 60-minute PET/MRI brain scan instead of a 15-minute PET/MRI brain scan.

Group IV healthy volunteers will not undergo any vertex-to-toe PET scans.

After completion of study treatment, intracranial tumor and recurrent glioblastoma participants are followed up every 3 months for 12 months.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University, School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Age ≥18 years old.

2. 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:

1. ANC ≥ 1.5 X 10^9/L w/o myeloid growth factor support for 7 d preceding lab assessment
2. 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
3. Platelet count ≥ 100 X 10^9/L w/o blood transfusions for 7 d preceding lab assessment
4. Bilirubin ≤ 1.5 X ULN except for pts w/ documented history of Gilbert's disease
5. ALT and AST ≤ 2.5 X ULN
6. Alkaline phosphatase (AP) ≤ 3 X ULN

7. Women of childbearing potential (WCBP): negative serum pregnancy test

   3. Ability to stand up and climb two steps with minimal assistance.

   4. Ability to understand and the willingness to sign a written informed consent document.

   5. (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.

   6. (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.

   7. (Part 3, GBM patients ONLY) Life expectancy of ≥ 6 months.

Exclusion Criteria:

1. Known allergy to adhesive tapes or other skin adhesives used in medical care

2. Subjects with the following co-morbid disease or incurrent illness:

   1. With known cirrhosis diagnosed with Child-Pugh Class A or higher liver disease.
   2. Severe/uncontrolled inter-current illness within the previous 28 days prior to PET scan
   3. Patients who have implantable devices that are contra-indicated for MRI
   4. Bleeding disorder
   5. Any other significant co-morbid conditions that in the opinion of the Investigator would impair study participation or cooperation.
   6. (Healthy volunteers ONLY - Part 1 and Part 4) prior or current malignancy
   7. (Healthy volunteers ONLY - Part 1 and Part 4) known kidney disease
3. Pregnant or nursing participants
4. History of allergic reactions to gadolinium-based MRI contrast agent
5. (Part 2, intracranial tumor patients ONLY) Other chemotherapy (besides what is being used to treat the intracranial tumor)
6. (Part 3, GBM patients ONLY) Has already begun therapy, prior to the first of two [18F]DASA-23 PET/MRI scans.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Procedure: Positron Emission Tomography; Undergo PET scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; Drug: Fluorine F 18 DASA-23; Given IV; Other Names: [18F]DASA-23; [18F]DASA23; 18F-DASA-23; 1-((2-Fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine; F18-labeled Pyruvate Kinase M2 Inhibitor DASA-23; F18-labeled PKM2 Inhibitor
Experimental: 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.	Procedure: Positron Emission Tomography; Undergo PET scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; Drug: Fluorine F 18 DASA-23; Given IV; Other Names: [18F]DASA-23; [18F]DASA23; 18F-DASA-23; 1-((2-Fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine; F18-labeled Pyruvate Kinase M2 Inhibitor DASA-23; F18-labeled PKM2 Inhibitor
Experimental: 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.	Procedure: Positron Emission Tomography; Undergo PET scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; Drug: Fluorine F 18 DASA-23; Given IV; Other Names: [18F]DASA-23; [18F]DASA23; 18F-DASA-23; 1-((2-Fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine; F18-labeled Pyruvate Kinase M2 Inhibitor DASA-23; F18-labeled PKM2 Inhibitor
Active Comparator: Group IV ([18F]DASA-23, PET); Healthy volunteers receive [18F]DASA-23 IV and undergo brain PET/MRI brain scan for 60 mins	Procedure: Positron Emission Tomography; Undergo PET scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; Drug: Fluorine F 18 DASA-23; Given IV; Other Names: [18F]DASA-23; [18F]DASA23; 18F-DASA-23; 1-((2-Fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine; F18-labeled Pyruvate Kinase M2 Inhibitor DASA-23; F18-labeled PKM2 Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in [18F]DASA-23 PET scan signal in patients with suspected recurrent glioblastoma	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.	From pre-treatment to one week after initiation of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of [18F]DASA-23 PET imaging in identifying intracranial tumors in patients with intracranial tumors.	Sensitivity will be reported as a percentage with 95% confidence interval.	Time of the [18F]DASA-23 PET scan
Specificity of [18F]DASA-23 PET imaging in identifying intracranial tumors in patients with intracranial tumors.	Specificity will be reported as a percentage with 95% confidence interval	Time of the [18F]DASA-23 PET scan
Accuracy of [18F]DASA-23 PET imaging in identifying intracranial tumors in patients with intracranial tumors.	Accuracy will be reported as a percentage with 95% confidence interval.	Time of the [18F]DASA-23 PET scan
Progression-free survival in patients with suspected recurrent glioblastoma	The percent change in SUV from the pre-treatment [18F]DASA-23 PET scan to the post-treatment [18F]DASA23 PET scan will be calculated. Patients will be divided into two groups based on whether their percent change in SUV is above or below the median. Kaplan-Meier curves for the two groups will be plotted and a log-rank test for difference in progression-free survival will be performed. A Cox proportional-hazards regression of progression-free survival on group will be performed. Progression-free survival will be reported as median survival time, with range.	Time from diagnosis up to 1 year
Overall survival in patients with suspected recurrent glioblastoma	The percent change in SUV from the pre-treatment [18F]DASA-23 PET scan to the post-treatment [18F]DASA23 PET scan will be calculated. Patients will be divided into two groups based on whether their percent change in SUV is above or below the median. Kaplan-Meier curves for the two groups will be plotted and a log-rank test for difference in overall survival will be performed. A Cox proportional-hazards regression of overall survival on group will be performed. Overall survival will be reported as median survival time, with range.	From time of initial diagnosis up to 2 years

Collaborators and Investigators

• Sponsor: Guido A. Davidzon, MD, SM
• Investigators: Principal Investigator: Guido A Davidzon, MD, Stanford Cancer Institute Palo Alto

Publications and helpful links

General Publications

• Beinat C, Patel CB, Haywood T, Shen B, Naya L, Gandhi H, Holley D, Khalighi M, Iagaru A, Davidzon G, Gambhir SS. Human biodistribution and radiation dosimetry of [18F]DASA-23, a PET probe targeting pyruvate kinase M2. Eur J Nucl Med Mol Imaging. 2020 Aug;47(9):2123-2130. doi: 10.1007/s00259-020-04687-0. Epub 2020 Jan 15.
• Beinat C, Patel CB, Xie Y, Gambhir SS. Evaluation of Glycolytic Response to Multiple Classes of Anti-glioblastoma Drugs by Noninvasive Measurement of Pyruvate Kinase M2 Using [18F]DASA-23. Mol Imaging Biol. 2020 Feb;22(1):124-133. doi: 10.1007/s11307-019-01353-2.

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2018
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: May 16, 2018
• First Submitted That Met QC Criteria: May 25, 2018
• First Posted (Actual): May 29, 2018

Study Record Updates

• Last Update Posted (Actual): August 12, 2024
• Last Update Submitted That Met QC Criteria: August 8, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Glioblastoma; Brain Neoplasms; Anti-Infective Agents; Antiparasitic Agents; Antinematodal Agents; Anthelmintics; Piperazine
• Other Study ID Numbers: IRB-44597; NCI-2018-00826 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 44597 (Other Identifier: Stanford IRB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No