Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at San Francisco, California
Dates
study started
estimated completion
Principal Investigator
by Robert Flavell, MD, PhD
Headshot of Robert Flavell
Robert Flavell

Description

Summary

CD46 is an exciting new therapeutic target in prostate cancer, with the antibody drug conjugate FOR46 under investigation in phase I clinical trials. The hypothesis of the study is that CD46 expression, measured via our novel imaging biomarker, is a characteristic feature of mCRPC, and particularly common in the most lethal forms of the disease including adenocarcinoma and Small-cell neuroendocrine carcinoma (SCNC). These data will provide crucial information about the feasibility of targeting cluster of differentiation 46 (CD46) in mCRPC, will be used guide the development of novel therapeutic and theranostic agents, to help develop treatments that improve outcomes for men with the most lethal forms of prostate cancer.

Official Title

A First-in-Human, Pilot PET Imaging Study of 89Zr-DFO-YS5, an immunoPET Agent for Detecting CD46 Positive Malignancy in Men With Prostate Cancer

Details

This single center imaging study involves one microdose of the imaging agent, followed by whole body PET imaging. Imaging data will be acquired in up to four PET studies to determine tumor and normal tissue uptake and dosimetry.

PRIMARY OBJECTIVES:

  1. To determine the optimal time point for imaging (based on analyzing the 4 scans of all participants using 89Zr-DFO-YS5 PET post-injection. (Cohort A)
  2. To determine the optimal antibody dose for imaging using 89Zr-DFO-YS5 PET. (Cohort B).
  3. To determine the sensitivity of metastatic lesion detection in mCRPC using 89Zr-DFO-YS5 PET as compared with conventional imaging.(Cohorts C & D)

SECONDARY OBJECTIVES:

  1. To determine the safety of 89Zr-DFO-YS5.
  2. To determine average organ uptake of 89Zr-DFO-YS5 (Cohort C & D).
  3. To descriptively report the patterns of intra-tumoral uptake of 89Zr-DFO-YS5 on whole body PET, including by site of disease, uptake by tumor type, inter-tumoral and inter-patient heterogeneity, and tumor-to-background signal (Cohorts C & D).

ARMS:

Cohort A: PET imaging data will be acquired up to four times to determine tumor and normal tissue uptake and dosimetry. The optimized scan time will be used for imaging in Cohorts B and C.

Cohort B: A dose of cold, non-radiolabeled antibody administered will be varied to determine the optimal antibody dose for image quality. The optimized antibody dose will be used in Cohort C and D. Participants will be followed for an additional 4-5 weeks after dose administration to assess for adverse events. Participants have the option to receive a repeat scan at the time of disease progression.

Cohort C: PET imaging will be acquired at the optimal time point and optimal antibody dose determined in Cohorts A & B. Participants in Cohort C have the option to receive a repeat scan at the time of disease progression.

Cohort D: PET imaging will be acquired at four time points using the antibody to enable calculation of tumor and organ dosimetry. This cohort enrolls concurrently with Cohort C.

All participants will be followed for up to 5 weeks after their first scan to assess for adverse events

Keywords

Prostate Cancer, Metastatic Castration-resistant Prostate Cancer, First-in-Human, immunoPET agent, CD46 positive malignancy, Prostatic Neoplasms, Antibodies, Immunoglobulins, 89Zr-DFO-YS5, YS5 antibody, Positron Emission Tomography (PET)/Computerized tomography (CT), Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI)

Eligibility

You can join if…

Open to people ages 18 years and up

  1. Participants must have histologically or cytologically confirmed metastatic, castration resistant prostate cancer (mCRPC).
  2. Age >=18 years
  3. Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Karnofsky >60%).
  4. Demonstrates adequate organ function as defined below:
    1. Total bilirubin <1.5 X upper limit of normal (ULN).
    2. Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase (SGOT)) <= 3 X institutional upper limit of normal (ULN).
    3. Alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase (SGPT)) <= 3 X institutional ULN.
    4. Creatinine clearance >= 60 mL/min, calculated using the Cockcroft-Gault equation.
  5. Ability to understand a written informed consent document, and the willingness to sign it.
  6. Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

You CAN'T join if...

  1. Patients who because of age, general medical, or psychiatric condition, or physiologic status cannot give valid informed consent.
  2. Any condition that, in the opinion of the Principal Investigator, would impair the patient's ability to comply with study procedures.
  3. Patients who have received the same antibody (YS5) earlier as part of therapy or detection.

Location

  • UCSF accepting new patients
    San Francisco California 94143 United States

Lead Scientist at UCSF

  • Robert Flavell, MD, PhD
    Robert Flavell, MD, PhD, is the Chief of Molecular Imaging and Therapeutics Clinical Section in the Department of Radiology and Biomedical Imaging at the University of California, San Francisco. He received his medical degree from Weill Cornell Medical College, and his PhD from the Rockefeller University as part of the Tri-Institutional MD PhD program.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Robert Flavell, MD, PhD
ID
NCT05245006
Phase
Phase 1 research study
Study Type
Interventional
Participants
Expecting 24 study participants
Last Updated