Fluoroethyltyrosine for Evaluation of Intracranial Neoplasms

Phase 2

Completed

Conditions: Low Grade Glioma
Recurrent WHO Grade III Glioma
Recurrent Glioblastoma
Recurrent World Health Organization (WHO) Grade II Glioma
Intracranial Neoplasm

Interventions: Drug: F-18 Fluoroethyltyrosine (FET)
Procedure: Positron Emission Tomography (PET)

Registration Number: NCT04044937

Lead Sponsor: Thomas Hope

Brief Summary: This phase II trial studies how well F-18 fluoroethyltyrosine (fluoroethyltyrosine) works in detecting tumors in participants with intracranial tumors that have come back. FET accumulates in malignant cells within intracranial neoplasms and can be used to detect recurrent disease and characterize the grade of glial neoplasms. Imaging agents such as FET can help oncologist to see the tumor better during a positron emission tomography (PET) scan.

Detailed Description: PRIMARY OBJECTIVES:

I. To determine if F-18 fluoroethyltyrosine (FET) PET can differentiate between benign treatment-related changes and recurrence in comparison to pathology in population 1 with recurrent metastatic disease and high-grade gliomas.

II. To determine if FET PET can accurately differentiate between low-grade and high-grade gliomas in population 2.

SECONDARY OBJECTIVES:

I. To determine if FET PET can differentiate between benign treatment-related changes and recurrence in comparison to pathology or imaging follow-up in population 1.

II. To determine if FET PET can differentiate between benign treatment-related changes and recurrence in comparison to pathology in population 1 with recurrent low-grade gliomas.

OUTLINE:

Participants receive F-18 fluoroethyltyrosine intravenously (IV) over approximately 1 minute and undergo PET over 40 minutes. After completion of study treatment, participants are followed up periodically.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 143

Inclusion Criteria

Age > 3 years.
Presence or suspicion of intracranial neoplasm in two populations.
- Population 1: Patients after primary treatment (radiation therapy and/or surgery) with suspicion of recurrence on magnetic resonance imaging (MRI). Three sub-populations will be considered:
  - Recurrent metastatic lesions.
  - Recurrent high-grade gliomas (grades 3 and 4).
  - Recurrent low-grade gliomas (grades 1 and 2).
- Population 2: Patients prior to primary treatment with planned biopsy or surgical resection.

Exclusion Criteria

Patient with known incompatibility to PET or computed tomography (CT)/MRI scans.
Patient unlikely to comply with study procedures, restrictions and requirements and judged by the investigator to be unsuitable for study participation.
- Sedation or anesthesia can be used for patients who cannot tolerate the exam.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Population 1: Intracranial neoplasms (glial or metastatic disease)	F-18 Fluoroethyltyrosine (FET)	Participants with intracranial neoplasms (glial or metastatic disease) with concern for recurrence or progression on conventional imaging (e.g., MRI) will receive F-18 fluoroethyltyrosine (FET) injected intravenously over approximately 1 minute and receive a single PET image lasting up to 40 minutes. Repeat FET PET will be offered to adult patients.
Population 2: Suspected glial neoplasms	Positron Emission Tomography (PET)	Participants with suspected glial neoplasms (Grade 2-4) planning to undergo a non-investigational biopsy or surgery prior to non-investigational, primary treatment (radiation therapy and/or surgery) will receive F-18 fluoroethyltyrosine (FET) injected intravenously over approximately 1 minute and receive a single PET image lasting up to 40 minutes. Repeat FET PET will be offered to adult patients.
Population 2: Suspected glial neoplasms	F-18 Fluoroethyltyrosine (FET)	Participants with suspected glial neoplasms (Grade 2-4) planning to undergo a non-investigational biopsy or surgery prior to non-investigational, primary treatment (radiation therapy and/or surgery) will receive F-18 fluoroethyltyrosine (FET) injected intravenously over approximately 1 minute and receive a single PET image lasting up to 40 minutes. Repeat FET PET will be offered to adult patients.
Population 1: Intracranial neoplasms (glial or metastatic disease)	Positron Emission Tomography (PET)	Participants with intracranial neoplasms (glial or metastatic disease) with concern for recurrence or progression on conventional imaging (e.g., MRI) will receive F-18 fluoroethyltyrosine (FET) injected intravenously over approximately 1 minute and receive a single PET image lasting up to 40 minutes. Repeat FET PET will be offered to adult patients.

Primary Outcome Measures

Name	Time	Method
Misclassification rate for either high grade or low grade in patients with suspected neoplasms (Population 2)	Up to 6 months	Readers will have access only to FET PET images for participants with suspected glial neoplasms (Grade 2-4) planning to undergo biopsy or surgery prior to primary treatment during evaluation and will grade the lesions in a binary fashion as having Grade II glial neoplasms or having Grade III/IV glial neoplasms. True positive (TP2): FET PET read as positive for Grade III/IV neoplasm, pathology demonstrates Grade III/IV neoplasm. False positive (FP2): FET PET read as positive for Grade III/IV neoplasm, pathology demonstrates Grade II neoplasm. True negative (TN2): FET PET read as positive for Grade II neoplasm, pathology demonstrates Grade II neoplasm. False negative (FN2): FET PET read as positive for Grade II neoplasm, pathology demonstrates Grade III/IV neoplasm. Misclassification rate = \[FP2+FN2\]/\[FP2+FN2+TP2+TN2\]
Misclassification rate for either having recurrent disease or not having recurrent disease for patients previously treated for glial and metastatic disease (Population 1)	Up to 6 months	Radiologists will classify lesions as having recurrent disease or not having recurrent disease. True Positives (TP) are defined as an FET PET read positive for tumor and pathology/follow-up demonstrates tumor recurrence in at least one biopsy sample, False positives (FP) are defined as an FET PET read positive for tumor and pathology/follow-up demonstrates negative tumor recurrence in all of the biopsy samples, True negatives (TN) are defined as an FET PET read as negative for tumor and pathology/follow-up also negative tumor recurrence in all of the biopsy samples and a false negative (FN) is defined as an FET PET read as negative for tumor and pathology/follow-up demonstrates tumor recurrence in at least one biopsy sample. Misclassification rate = \[FP+FN)\]/\[FP+FN+TP+TN\]

Secondary Outcome Measures

Name	Time	Method
Misclassification rate for FET PET in the evaluation of recurrent low-grade gliomas (Population 1)	Up to 6 months	Low-grade glioma is defined by low uptake of FET. Radiologists will classify lesions based on imaging as either having recurrent disease or not having recurrent disease. True Positives (TP1L) are defined as an FET PET read positive for low-grade tumor and pathology/follow-up demonstrates low-grade tumor recurrence in at least one biopsy sample, False positives (FP1L) are defined as an FET PET read positive for low grade tumor recurrence and pathology/follow-up demonstrates negative low-grade tumor recurrence in all of the biopsy samples, True negatives (TN1L) are defined as an FET PET read as negative for low-grade tumor recurrence and pathology/follow-up also negative for low grade tumor recurrence in all of the biopsy samples and a false negative (FN1L) is defined as an FET PET read as negative for low grade tumor recurrence and pathology/follow-up demonstrates low grade tumor recurrence in at least one biopsy sample. Misclassification rate = \[FP1L+FN1L)\]/\[FP1L+FN1L+TP1L+TN1L\]
Binary characterization of follow-up imaging as positive/negative for tumor recurrence	Up to 6 months	Participants with available histology (performed within 4 weeks of FET scans) or follow-up imaging (performed within 6 months of FET scan) will be included and a composite truth standard for recurrence or treatment-related changes will be evaluated for each case. In the absence of pathology, the composite truth standard will use available clinical information to make a determination. Positive for tumor recurrence on follow-up imaging will be based on Response assessment in neuro-oncology criteria (RANO) criteria reads. Follow-up imaging has to be performed within six months of the FET PET imaging study to be considered for evaluation. Additionally, the composite truth standard may consider tumor board notes and subsequent management of the patient to make a determination.
Degree of inter-rater reliability for tracer uptake	Up to 6 months	Fleiss' kappa statistic will be used to determine the agreement between the assessment of FET-PET tumor targeting (tracer uptake in target lesion: yes/ no), as assessed by three independent blinded readers. Scores range from 0 to 1 with higher scores indicating a great degree of agreement
Degree of inter-rater reliability for radiological interpretations	Up to 6 months	Cohen's kappa statistics will be used to determine the reproducibility of the assessment by individual readers when analyzing the same data repeatedly and measures the agreement between two raters who each classify items into mutually exclusive categories.