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

NCT03539731 | Terminated Phase 1 FDA Drug

• 3 other identifiers: IRB-44597NCI-2018-0082644597
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Subject; Intracranial Neoplasm; Glioblastoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

• Overall survival in patients with suspected recurrent glioblastoma

  From time of initial diagnosis up to 2 years

Study Arms (4)

Group I ([18F]DASA-23, PET)

ACTIVE COMPARATOR

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.

Drug: Fluorine F 18 DASA-23; Procedure: Positron Emission Tomography

Group II ([18F]DASA-23, PET)

EXPERIMENTAL

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.

Drug: Fluorine F 18 DASA-23; Procedure: Positron Emission Tomography

Group III ([18F]DASA-23, PET)

EXPERIMENTAL

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.

Drug: Fluorine F 18 DASA-23; Procedure: Positron Emission Tomography

Group IV ([18F]DASA-23, PET)

ACTIVE COMPARATOR

Healthy volunteers receive \[18F\]DASA-23 IV and undergo brain PET/MRI brain scan for 60 mins

Drug: Fluorine F 18 DASA-23; Procedure: Positron Emission Tomography

Interventions

Fluorine F 18 DASA-23 DRUG

Given IV

Also known as: [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

Group I ([18F]DASA-23, PET); Group II ([18F]DASA-23, PET); Group III ([18F]DASA-23, PET); Group IV ([18F]DASA-23, PET)

Positron Emission Tomography PROCEDURE

Undergo PET scan

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging

Group I ([18F]DASA-23, PET); Group II ([18F]DASA-23, PET); Group III ([18F]DASA-23, PET); Group IV ([18F]DASA-23, PET)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Guido A. Davidzon, MD, SM: lead

Study Sites (1)

Stanford University, School of Medicine

Palo Alto, California, 94304, United States

Location

Related Publications (2)

• 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.

  PMID: 31938892 DERIVED

• 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.

  PMID: 30989436 DERIVED

MeSH Terms

Conditions

Brain Neoplasms; Glioblastoma

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Guido A Davidzon, MD

  Stanford Cancer Institute Palo Alto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: May 16, 2018
• First Posted: May 29, 2018
• Study Start: April 23, 2018
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: August 12, 2024

Record last verified: 2024-08

Locations

US (1)