[18F]Fluciclovine and [18F]FLT PET/CT Assessment of Primary High-Grade Brain Tumors

NCT03276676 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: HCI104704
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The hypothesis of this exploratory clinical trial in patients with high-grade a primary brain tumor who receive chemoradiation is that the PET imaging agents \[18F\]Fluciclovine and/or \[18F\]FLT will be a better predictor of tumor response than standard MRI based brain tumor response criteria. When used in conjunction, the two PET agents may be better able to predict tumor aggressiveness and thus overall survival than the use of individual-tracer PET biomarkers. This may eventually lead to improved assessment of response (including time to progression and overall survival) and differentiation of tumor recurrence/progression from treatment effect (pseudoprogression).

Conditions

Brain Tumor

Outcome Measures

Primary Outcomes (1)

• Count of Patients Showing >25% Reduction in Cerebral Uptake of [18F]FLT and [18F]Fluciclovine

  Cerebral uptake of \[18F\]FLT and \[18F\]Fluciclovine measured in terms of SUVmax and SUVmean at each imaging time point ((1) prior to any tumor-directed therapy, (2) within 1-4 weeks after the conclusion of the initial (\~6-8 weeks) chemoradiotherapy, and (3) following suspected recurrence/progression versus treatment effect (pseudoprogression) shown with MRI, within 6 months of the completion of chemoradiation). Using the first time point as baseline for the following two time points, the percent change is calculated from SUVmean and SUVmax for each of the radiotracers studied in this trial. This measure only applies to Group A, as multiple time points of scan data are needed to calculate change in uptake.

  (1) Baseline [18F]FLT and [18F]Fluciclovine scans were acquired prior to initiating therapy, follow-up scans were acquired (2) 1-4 weeks following conclusion of initial chemoradiation, and (3) within 6 months of completion of chemoradiation.

Study Arms (2)

Group A

EXPERIMENTAL

Participants enrolled in Group A will undergo a maximum of 6 scans throughout this study. \[18F\]FLT- and \[18F\]Fluciclovine-PET/CT scans at up to three imaging time points: (1) prior to any tumor-directed therapy, (2) within 1-4 weeks after the conclusion of the intitial (\~6-8 weeks) chemoradiotherapy, and (3) following suspected recurrence/progression versus treatment effect (pseudoprogression) shown with MRI, within 6 months of the completion of chemoradiation

Drug: [18F]FLT; Drug: [18F]Fluciclovine

Group B

EXPERIMENTAL

Participants enrolled in Group B will undergo 2 scans as part of this study. \[18F\]FLT- and \[18F\]Fluciclovine-PET/CT scans will be acquired at a single timepoint, at the time of suspected pseudoprogression.

Drug: [18F]FLT; Drug: [18F]Fluciclovine

Interventions

[18F]FLT DRUG

PET exams of \[18F\]FLT will be acquired in each patient at up to three time points: (1) prior to any tumor-directed therapy, either prior to surgery or immediately after surgery providing a complete surgical resection was not performed and confirmed by a post-operative contrast MRI scan where residual tumor \> 1.0 cm in diameter was present and prior to any tumor-directed therapy; (2) at the conclusions of the initial (\~6-8 weeks) chemoradiotherapy; and (3) patients with MRI-documented possible recurrence/progression versus treatment effect (pseudoprogression) within 6 months from the time of completion of chemoradiation.

Group A; Group B

[18F]Fluciclovine DRUG

PET exams of \[18F\]Fluciclovine will be acquired in each patient at up to three time points: (1) prior to any tumor-directed therapy, either prior to surgery or immediately after surgery providing a complete surgical resection was not performed and confirmed by a post-operative contrast MRI scan where residual tumor \> 1.0 cm in diameter was present and prior to any tumor-directed therapy; (2) at the conclusions of the initial (\~6-8 weeks) chemoradiotherapy; and (3) patients with MRI-documented possible recurrence/progression versus treatment effect (pseudoprogression) within 6 months from the time of completion of chemoradiation.

Group A; Group B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Group A: Patients where there is compelling evidence, based on the MRI and/or CT imaging, that a high-grade primary brain tumor is present. Pathologic confirmation will occur with biopsy or surgery.
• Patients whose tumor is felt to be inoperable and a biopsy is performed but no surgery.
• Patients with a newly diagnosed primary malignant brain tumor (WHO Grade III or IV) who will be receiving chemoradiation and who either did not undergo surgical resection or underwent incomplete resection with residual tumor \> 1.0 cm in greatest diameter by contrast MRI postoperatively.
• Group B: Patients with pathologically proven malignant brain tumor (WHO Grade III or IV glial-based tumors) who have undergone chemoradiation and have MRI-documented possible recurrence/progression versus treatment effect (pseudoprogression) within 6 months from the time of completion of chemoradiation.
• Patients must document their willingness to be followed for at least 24 months after recruitment by signing informed consent documenting their agreement to have clinical endpoints and the results of histopathologic tissue analysis (when tissue becomes available from routine care) entered into a research database.
• All patients, or their legal guardians, must sign a written informed consent and HIPAA authorization in accordance with institutional guidelines.
• Determination of pregnancy status: Female patients who are not postmenopausal or surgically sterile will undergo a serum pregnancy test prior to each set of \[18F\]FLT and \[18F\]Fluciclovine PET scans. A negative test will be necessary for such patients to undergo research PET imaging.
• Pre-imaging laboratory tests must be performed within 28 days prior to the \[18F\]FLT imaging procedure. These must be less than 4.0 times below or above the upper or lower limit range for the respective laboratory test for entry into the study (unless clinically not relevant). In those instances where a laboratory value is outside of this range, then such a patient will be ineligible for enrollment unless at the discretion of the PI the abnormal lab value is of no clinical significance to the safety or integrity of the study results. . For follow-up scanning sessions after therapy has been instituted, laboratory testing will also be required due to the use of \[18F\]FLT. The patients have brain tumors and will have received chemoradiation; therefore, many routine laboratory tests may not be within the typical normal range. As such, a factor of 4.0 times above or below the upper or lower value for the normal range for any laboratory test will also be used to determine the acceptable range for the 2nd and possibly 3rd imaging time points (unless clinically not relevant as explained above). The baseline laboratory testing will include liver enzymes (ALT, AST), bilirubin (total), serum electrolytes, CBC with platelets, prothrombin time, partial thromboplastin time, BUN, and creatinine. For those patients receiving coumadin or another anticoagulant the upper limit for prothrombin time or partial thromboplastin time must not exceed 6 times the upper limit of the normal range. (Appendix E, Laboratory Study Results).

You may not qualify if:

• Patients with clinically significant signs of uncal herniation, such as acute pupillary enlargement, rapidly developing motor changes (over hours), or rapidly decreasing level of consciousness, are not eligible.
• Patients with known allergic or hypersensitivity reactions to previously administered radiopharmaceuticals. Patients with significant drug or other allergies or autoimmune diseases may be enrolled at the Investigator's discretion.
• Patients who are pregnant or lactating or who suspect they might be pregnant. Serum pregnancy tests will be obtained prior to each set of multi-tracer PET scans in female patients that are not postmenopausal or surgically sterile.
• Adult patients who require monitored anesthesia for PET scanning.
• Patients who are too claustrophobic to undergo PET scanning.
• Known HIV positive patients due to the previous toxicity noted with \[18F\]FLT in this patient group.

Sponsors & Collaborators

• University of Utah: lead
• Blue Earth Diagnostics: collaborator

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Brain Neoplasms

Interventions

alovudine; fluciclovine F-18

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Sam Mitchell
• Organization: Huntsman Cancer Institute, Center for Quantitative Cancer Imaging

sam.mitchell@hci.utah.edu

801-213-6110

Study Officials

• Jeffrey Yap, PhD

  University of Utah

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Both arms will undergo the same interventions, however, Group A will undergo three imaging sessions and Group B will undergo one imaging session

Study Record Dates

• First Submitted: September 5, 2017
• First Posted: September 8, 2017
• Study Start: September 24, 2018
• Primary Completion: April 12, 2021
• Study Completion: August 18, 2023
• Last Updated: December 27, 2024
• Results First Posted: December 27, 2024

Record last verified: 2024-10

Locations

US (1)