Advanced Solid Tumor, Bladder Cancer, Bladder Neoplasm, Nerve Sheath Neoplasms, Nerve Sheath Tumor, Nerve Sheath Tumor, Nos, Nerve Sheath Tumors, Solid Carcinoma, Solid Tumor, Adult, Solid Tumor Cancer, Solid Tumor Malignancies, Solid Tumor Neoplasms
Conditions
Keywords
Imaging Study
Brief summary
This is a single-center, pilot, PET-imaging study of the novel radiotracer 89Zirconium-89 DFO conjugated to the YS5 monoclonal antibody (\[89Zr\]DFO-YS5) in participants with nerve sheath tumor, bladder cancer, or advanced solid tumor neoplasms.
Detailed description
PRIMARY OBJECTIVE: I. To descriptively report patterns of \[89Zr\]DFO-YS5 uptake on whole-body PET. SECONDARY OBJECTIVE: II. To determine the safety of \[89Zr\]DFO-YS5. OUTLINE: Participants will be administered a single dose of \[89Zr\]DFO-YS5 followed by whole-body positron emission tomography (PET) imaging at a single time point. All participants will be followed for adverse events for approximately Participants in the main study will be followed for adverse events for approximately 1 month after \[89Zr\]DFO-YS5 radiotracer administration.
Interventions
DRUG[89Zr]DFO-YS5
Given intravenously (IV)
PROCEDUREPositron Emission Tomography (PET)-Magnetic resonance imaging (MRI)
Participants may receive a whole-body PET-MRI or a whole body PET-CT
PROCEDUREPositron Emission Tomography (PET)-Computerized tomography (CT)
Participants may receive a whole-body PET-CT or a whole-body PET-MRI
Sponsors
Robert Flavell, MD, PhD
Kyntra Bio
Fortis Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histological or cytological confirmation of malignant peripheral nerve sheath tumor, bladder cancer, or solid tumor neoplasm. 2. At least one soft tissue lesion measurable at 1 cm or greater in short axis measurement on cross sectional imaging such as Computerized tomography (CT), magnetic resonance imaging (MRI), or Positron Emission Tomography (PET)/CT (scan imaging as documented in the medical record). Exception: For participants with localized bladder cancer (pre-cystectomy), lesions smaller than 1 centimeter (cm) are permitted, provided there is cystoscopic confirmation of a bladder mass. 3. Clinically able to undergo PET-CT imaging or PET-MRI. 4. Age ≥ 18 years. 5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 or Karnofsky ≥ 50% (see Appendix 1). 6. Adequate organ function as defined below: * Total bilirubin: ≤ 1.5 x institutional upper limit of normal (ULN) (unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits). * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)): ≤ 3 x ULN. * Alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase (SGPT)): ≤ 3 x ULN. * Estimated creatinine clearance: ≥ 60 mL/min, calculated using the Cockcroft-Gault equation. 7. Females of reproductive potential (defined below) must be willing to undergo a urine or serum pregnancy test (i.e., human chorionic gonadotropin test) within 72 hours before administration of \[89Zr\]DFO-YS5. A female is considered to NOT be of reproductive potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice), if they meet 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). The result of the urine or serum pregnancy test must be negative in order to initiate the \[89Zr\]DFO-YS5 administration. If a urine pregnancy test is positive or equivocal, a confirmatory a serum pregnancy test is required. The individual must be excluded from participation if the serum pregnancy result is positive. Pregnant individuals are excluded from this study because there is an unknown but potential risk for adverse effects in the unborn child secondary to treatment of the study participant with \[89Zr\]DFO-YS5. 8. Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or endpoints of this study are eligible. 9. Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
1. Individuals with a contraindication to PET-CT imaging (e.g., severe claustrophobia) or PET-MRI (e.g., implanted devices, metallic objects, or other implants). Participants must be able to undergo either PET-CT or PET-MRI. 2. Individuals who are pregnant or breastfeeding/chest-feeding. Pregnant and breastfeeding/chest-feeding individuals are excluded because there is an unknown but potential risk for adverse effects in the unborn/nursing child secondary to treatment of the study participant with \[89Zr\]DFO-YS5. Females of childbearing potential must have a negative pregnancy test before administration of \[89Zr\]DFO-YS5, as outlined in inclusion criterion #7. Breastfeeding/chest-feeding should be discontinued before administration of \[89Zr\]DFO-YS5. 3. Individuals who do not agree to follow the below contraception requirements: Females of reproductive potential (defined below) must agree to use two forms of contraception, consisting of a barrier method (such as condoms) in combination with a secondary complementary method (such as hormonal, Intrauterine device (IUD), etc.), or strict abstinence, for the duration of study participation and for 1 month after administration of \[89Zr\]DFO-YS5. A female is considered to NOT be of reproductive potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice), if they meet 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). 4. Hypersensitivity to \[89Zr\]DFO-YS5 or any of its excipients. 5. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean maximum standard uptake value (SUVmax-avg) on Positron Emission Tomography (PET) scan | Up to 8 days | A volume of interest (VOI) will be placed around each lesion, and the calculated maximum standard uptake value (SUVmax) will be recorded for each lesion. Adjusted SUVmax data will then be averaged across up to 15 lesions within a given patient (SUVmax-avg) at each time point. In order to avoid clustering effects, analyses will be limited to the five largest osseous metastases, five largest lymph node metastases, and five largest visceral/soft tissue metastases. Metastatic lesion location, size (bidimensional axial measurement), and SUVmax will be tabulated. This will be conducted for all lesions. |
| Median intra-tumoral SUVmax | Up to 8 days | The median and range for intra-tumoral SUVmax within metastatic lesions will be descriptively reported, to assess for intra-tumoral heterogeneity and differences in uptake by site of disease. |
| Tumor-to-background signal (Ratio) | Up to 8 days | The tumor-to-background signal refers to comparing the standardized uptake value (SUV) of a lesion (tumor) to the SUV of a nearby normal organ or tissue that serves as a "background" reference. The ratio of the tumor-to-background signal on PET scan (normal organ as background uptake values) will be calculated as the SUVmax of tumor divided by the SUV of background organ |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with reported treatment-emergent adverse events | Up to 8 days | The proportion of participants with reported treatment-emergent Adverse events (AEs) will be classified and graded according to the NCI CTCAE version. 5.0 by severity and type evaluated from the time of administration through the Day 6-8 Visit (120-168 hours post-dose). |
Countries
United States
Contacts
CONTACTMaya Aslam
PRINCIPAL_INVESTIGATORRobert Flavell, MD
University of California, San Francisco
Outcome results
None listed