Imaging of Solid Tumors Using 18F-TRX

PRIMARY OBJECTIVE:

I. To determine the safety of fluorine F 18 trioxolane (18F-TRX) in participants with any solid tumor malignancy with at least 3 metastatic lesions on conventional imaging (Cohort 1); or known or presumed high grade glioma, locally advanced metastatic clear cell renal cell carcinoma with at least 3 lesions on conventional imaging, and metastatic castration-resistant prostate cancer (mCRPC) with at least 1 metastatic lesion on conventional imaging (Cohort 2).

SECONDARY OBJECTIVES:

I. To determine the organ dosimetry and pharmacokinetics of 18F-TRX (Cohort 1).

II. To determine the sensitivity for detection of malignant lesions with 18F-TRX PET in participants with metastatic castration-resistant prostate cancer (n = 30), locally advanced or metastatic clear cell renal cell carcinoma (n = 10), and World Health Organization (WHO) grade 3 or 4 glioma (n = 10) (Cohort 2).

III. To determine the feasibility of lesion detection using 18F-TRX in participants with known or presumed high grade glioma, locally advanced metastatic clear cell renal cell carcinoma with at least 3 lesions on conventional imaging, and mCRPC with at least 1 metastatic lesion on conventional imaging (Cohort 2).

EXPLORATORY OBJECTIVE:

I. To correlate 18F-TRX uptake with Six-Transmembrane Epithelial Antigen of Prostate 3 (STEAP3) expression determined by immunohistochemistry (IHC) evaluation of tumor tissue obtained within 3 months of PET.

OUTLINE:

Participants are assigned to 1 of 2 cohorts:

COHORT 1: Participants receive 18F-TRX intravenously (IV) and undergo up to 8 PET/CT or PET/MRI scans.

COHORT 2: Participants receive 18F-TRX IV and undergo a single scan.

After completion of study intervention, patients are followed up 1-7 days post-injection.

Inclusion criteria

• Age ≥ 18 years
• Advanced solid tumor malignancy in one of the following cohorts:

• Cohort 1 (n = 6): Any solid tumor malignancy with at least 3 metastatic lesions on conventional imaging
• Cohort 2 (n = 50):

• WHO grade 3 or 4 glioma - patients with known (by integrated molecular and histopathologic diagnosis) or presumed (by imaging; e.g., enhancing necrotic and/or hypervascular intrinsic brain tumor) high grade (WHO grade 3 or 4) glioma (n = 10), Locally advanced or metastatic clear cell renal cell carcinoma with at least three metastatic lesions on conventional imaging (n = 10).
• Metastatic castration-resistant prostate cancer with at least one metastatic lesion on conventional imaging including cross-sectional imaging of the chest, abdomen and pelvis and whole body bone scan or prostate-specific membrane antigen (PSMA) PET scan (n = 30).
• Ability to understand and the willingness to sign a written informed consent document.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Negative serum or urine pregnancy test (women of childbearing potential only) within 72 hours of baseline procedures.
• Absolute neutrophil count > 1.5 x 10^6/L.
• Platelets > 75,000 x 10^6/L.
• Hemoglobin > 8 g/dL.
• Total bilirubin < 1.5 x upper limit of normal.
• Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase (SGOT)) < 2.5 x upper limit of normal (< 5 x upper limit of normal in patients with liver metastases on conventional imaging).
• Alanine aminotransferase (ALT)(serum glutamic-pyruvic transaminase (SGPT)) < 2.5 x upper limit of normal (< 5 x upper limit of normal in patients with liver metastases on conventional imaging).
• Creatinine clearance > 50 ml/min, calculated using the Cockcroft-Gault equation.

Exclusion criteria

• Individuals with any condition or social circumstance that, in the opinion of the investigator, would impair the participant's ability to comply with study procedures.
• Individuals receiving strong inhibitors or inducers of CYP3A4.
• Uncontrolled active infection or other medical condition that would preclude safe participation in the study as judged by the Investigator.
• Individuals who are pregnant.

• Individuals of childbearing potential (defined below) must agree to undergo a urine pregnancy test prior to participating in the study scans. Pregnant individuals are excluded because there is an unknown but potential risk for adverse effects in the unborn child secondary to administration of 18F-TRX to the study participant.
• A female is considered to not be of childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice), if the participant meets either of the following two criteria: (1) has reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause); or (2) has undergone surgical sterilization (i.e., hysterectomy and/or bilateral oophorectomy for removal of uterus and/or ovaries).
• Individuals who are breastfeeding/chestfeeding.

• Breastfeeding/chestfeeding individuals are excluded because there is an unknown but potential risk for adverse effects in the unborn/nursing child secondary to administration of 18F-TRX to the study participant.
• Breastfeeding/chestfeeding should be discontinued before administration of 18F-TRX.