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PET Imaging Study of 89Zr-DFO-YS5

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ClinicalTrials.gov Identifier: NCT05245006
Recruitment Status : Recruiting
First Posted : February 17, 2022
Last Update Posted : March 31, 2022
Sponsor:
Collaborators:
United States Department of Defense
Fortis Therapeutics, Inc.
Information provided by (Responsible Party):
Robert Flavell, MD, PhD, University of California, San Francisco

Brief 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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Metastatic Castration-resistant Prostate Cancer Drug: 89Zr-DFO-YS5 Biological: YS5 antibody Procedure: Positron Emission Tomography (PET)/Computerized tomography (CT) Procedure: Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI) Phase 1

Detailed Description:

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.(Cohort C)

SECONDARY OBJECTIVES:

  1. To determine the safety of 89Zr-DFO-YS5.
  2. To determine average organ uptake of 89Zr-DFO-YS5.
  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.

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. Participants in Cohort A will be followed throughout the course of their scan(s).

Cohort B: The dose of cold, non-radiolabeled antibody administered will be varied, to determine the optimal antibody dose for image quality and participants will be followed for an additional three weeks after dose administration to assess for adverse events. The optimized cold antibody dose will be used for imaging in Cohort C.

Cohort C: PET imaging will be acquired at the optimal time point and antibody dose following 89Zr-DFO-YS5, and participants will be followed for an additional three weeks after dose administration to assess for adverse events, and until progression. Participants in this cohort will have the option to receive a repeat 89Zr-DFO-YS5 PET at the time of disease progression.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
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
Actual Study Start Date : March 18, 2022
Estimated Primary Completion Date : December 31, 2025
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort A: 89Zr-DFO-YS5
Participants receive one dose of 89Zr-DFO-YS5 up to 3 millicurie (mCi), and undergo a whole body PET performed at 1-4 hours, approximately 20-28 hours, 48-96 hours, and 120-168 hours post injection for up to 4 scans total.
Drug: 89Zr-DFO-YS5
3 mCi will be administered intravenously
Other Names:
  • immunoPET agent
  • Imaging Agent

Procedure: Positron Emission Tomography (PET)/Computerized tomography (CT)
Imaging which combines a CT scan and a PET scan
Other Names:
  • PET/CT
  • PET/CT Scan
  • Whole Body PET/CT

Procedure: Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI)
Imaging which combines an MRI scan and a PET scan
Other Names:
  • PET/CT
  • PET/MRI Scan
  • Whole Body PET/MRI

Experimental: Cohort B: YS5, 89Zr-DFO-YS5, Multiple Scans
89Zr-DFO-YS5 will be co-administered with unlabeled YS5 antibody. Participants will receive either 20 mg or 50 mg of YS5 prior to imaging and administration of 89Zr-DFO-YS5 and whole body PET scan performed at 1-4 hours, approximately 20-28 hours, 48-96 hours, and 120-168 hours post injection for up to 4 scans total.
Drug: 89Zr-DFO-YS5
3 mCi will be administered intravenously
Other Names:
  • immunoPET agent
  • Imaging Agent

Biological: YS5 antibody
20 or 50 mg administered intravenously
Other Names:
  • YS5
  • Unmodified YS5 antibody

Procedure: Positron Emission Tomography (PET)/Computerized tomography (CT)
Imaging which combines a CT scan and a PET scan
Other Names:
  • PET/CT
  • PET/CT Scan
  • Whole Body PET/CT

Procedure: Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI)
Imaging which combines an MRI scan and a PET scan
Other Names:
  • PET/CT
  • PET/MRI Scan
  • Whole Body PET/MRI

Experimental: Cohort C: YS5, 89Zr-DFO-YS5 with scan at progression
89Zr-DFO-YS5 will be co-administered with unlabeled YS5 antibody prior to PET imaging for a single scan. Participants in have the option to receive a repeat 89Zr-DFO-YS5 PET at the time of disease progression.
Drug: 89Zr-DFO-YS5
3 mCi will be administered intravenously
Other Names:
  • immunoPET agent
  • Imaging Agent

Biological: YS5 antibody
20 or 50 mg administered intravenously
Other Names:
  • YS5
  • Unmodified YS5 antibody

Procedure: Positron Emission Tomography (PET)/Computerized tomography (CT)
Imaging which combines a CT scan and a PET scan
Other Names:
  • PET/CT
  • PET/CT Scan
  • Whole Body PET/CT

Procedure: Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI)
Imaging which combines an MRI scan and a PET scan
Other Names:
  • PET/CT
  • PET/MRI Scan
  • Whole Body PET/MRI




Primary Outcome Measures :
  1. Optimal time point for imaging using 89Zr-DFO-YS5 PET post-injection (Cohort A) [ Time Frame: Up to 7 days ]
    For Cohort A, the optimal time point will be selected based on optimal maximun Standardized uptake value (SUVmax) of metastatic lesions, and ratio of SUVmax to blood pool. Due to the limited samples, the investigator will use all available lesions without considering the location of the lesions or the possible intra-correlation of the lesions from the same participant.

  2. Optimal antibody dose for imaging using 89Zr-DFO-YS5 PET (Cohort B) [ Time Frame: Up to 7 days ]
    For Cohort B, the optimal dose of antibody will be selected based on the optimal SUVmax of metastatic lesions, and ratio of SUVmax to blood pool. Due to the limited samples, the investigator will use all available lesions without considering the location of the lesions or the possible intra-correlation of the lesions from the same participant.

  3. Proportion of participants with metastatic lesions accurately detected in mCRPC using 89Zr-DFO-YS5 PET (sensitivity) (Cohort C) [ Time Frame: Up to 24 months ]
    Sensitivity is the probability that a test will indicate disease among those with the actual disease: True Positive / (True Positive + False Negative). Lesions will be graded on a semi-quantitative scale ranging from 1-5 as is common for 89Zr-antibody human imaging studies (1 = no uptake, 2 = probably no uptake, 3 = equivocal, 4 = probably positive, 5 = definitely positive). Using as a cut-off to 4 or 5 on the semi-quantitative scale, the sensitivity of 89Zr-DFO-YS5 PET will be descriptively reported on a lesion-per-lesion basis, using as reference standard staging scans including CT or MRI of the chest/abdomen/pelvis and whole body bone scan. The sensitivity estimate will be based on lesion level without considering the location of the lesions or the possible intra-correlation of the lesions from the same patient.

  4. Median SUVmax [ Time Frame: Up to 24 months ]
    The median and range of SUVmax across all metastatic lesions per participant will be descriptively reported using mediastinal blood pool and normal organ as background uptake values

  5. Average SUVmax (SUVmax-ave) [ Time Frame: Up to 24 months ]
    The average SUVmax-ave across all metastatic lesions per participant will be descriptively reported using mediastinal blood pool and normal organ as background uptake values.


Secondary Outcome Measures :
  1. Proportion of participants with treatment-related Adverse Events [ Time Frame: Up to 3 weeks after last dose administration, approximately 35 days ]
    The frequency and severity of adverse events following Zr-DFO-YS5 injection will be descriptively reported, using CTCAE version 5.0

  2. Average organ uptake of 89Zr-DFO-YS5 [ Time Frame: Up to 24 months ]
    Average organ uptake of 89Zr-DFO-YS5 on PET will be estimated.

  3. Intra-tumoral uptake of 89Zr-DFO-YS5 by tumor type (Cohort C) [ Time Frame: Up to 24 months ]
    The median and range for intra-tumoral SUVmax within metastatic lesions will be descriptively reported

  4. Intra-tumoral uptake of 89Zr-DFO-YS5 by Site of Disease (Cohort C) [ Time Frame: Up to 24 months ]
    The median and range for intra-tumoral SUVmax within metastatic lesions will be descriptively reported

  5. Inter-tumoral heterogeneity (Cohort C) [ Time Frame: Up to 24 months ]
    The median and range for intra-tumoral SUVmax within metastatic lesions will be descriptively reported to assess for Inter-tumoral heterogeneity.

  6. Inter-participant heterogeneity (Cohort C) [ Time Frame: Up to 24 months ]
    The median and range for intra-tumoral SUVmax within metastatic lesions will be descriptively reported to assess for Inter-participant heterogeneity

  7. Tumor-to-background signal (Cohort C) [ Time Frame: Up to 24 months ]
    The median and range for intra-tumoral SUVmax within metastatic lesions will be descriptively reported



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  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)(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.
  7. Currently progressing by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria at the time of study entry.

Exclusion Criteria:

  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05245006


Contacts
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Contact: Maya Aslam 877-827-3222 Maya.Aslam@ucsf.edu

Locations
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United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Maya Aslam       Maya.Aslam@ucsf.edu   
Contact    877-827-3222    cancertrials@ucsf.edu   
Principal Investigator: Robert Flavell, MD, PhD         
Sponsors and Collaborators
Robert Flavell, MD, PhD
United States Department of Defense
Fortis Therapeutics, Inc.
Investigators
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Principal Investigator: Robert Flavell, MD, PhD University of California, San Francisco
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Responsible Party: Robert Flavell, MD, PhD, Principal Investigator, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT05245006    
Other Study ID Numbers: 209210
NCI-2022-01310 ( Registry Identifier: NCI Clinical Trials Reporting Program (CTRP) )
First Posted: February 17, 2022    Key Record Dates
Last Update Posted: March 31, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Robert Flavell, MD, PhD, University of California, San Francisco:
First-in-Human
immunoPET agent
CD46 positive malignancy
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Antibodies
Immunoglobulins
Immunologic Factors
Physiological Effects of Drugs