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

G

Guido A. Davidzon, MD, SM

Status and phase

Terminated
Phase 1

Conditions

Intracranial Neoplasm
Healthy Subject
Glioblastoma

Treatments

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

Study type

Interventional

Funder types

Other

Identifiers

NCT03539731
44597 (Other Identifier)
IRB-44597
NCI-2018-00826 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

27 patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Age ≥18 years old.

  1. 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:

  2. ANC ≥ 1.5 X 10^9/L w/o myeloid growth factor support for 7 d preceding lab assessment

  3. 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

  4. Platelet count ≥ 100 X 10^9/L w/o blood transfusions for 7 d preceding lab assessment

  5. Bilirubin ≤ 1.5 X ULN except for pts w/ documented history of Gilbert's disease

  6. ALT and AST ≤ 2.5 X ULN

  7. Alkaline phosphatase (AP) ≤ 3 X ULN

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

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

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

    3. (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.

    4. (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.

    5. (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.

Trial design

Primary purpose

Diagnostic

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

27 participants in 4 patient groups

Group I ([18F]DASA-23, PET)
Active Comparator group
Description:
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.
Treatment:
Procedure: Positron Emission Tomography
Drug: Fluorine F 18 DASA-23
Group II ([18F]DASA-23, PET)
Experimental group
Description:
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.
Treatment:
Procedure: Positron Emission Tomography
Drug: Fluorine F 18 DASA-23
Group III ([18F]DASA-23, PET)
Experimental group
Description:
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.
Treatment:
Procedure: Positron Emission Tomography
Drug: Fluorine F 18 DASA-23
Group IV ([18F]DASA-23, PET)
Active Comparator group
Description:
Healthy volunteers receive \[18F\]DASA-23 IV and undergo brain PET/MRI brain scan for 60 mins
Treatment:
Procedure: Positron Emission Tomography
Drug: Fluorine F 18 DASA-23

Trial contacts and locations

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Data sourced from clinicaltrials.gov

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