64Cu-GRIP B in Patients With Advanced Genitourinary Malignancies

a study on Prostate Cancer Kidney Cancer Urethral Cancer Kidney Neoplasm

Summary

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

Description

Summary

This is a first-in-human phase I/II imaging study of 64Cu-GRIP B PET in patients with advanced genitourinary (GU) malignancies. The tracer is designed to detect extracellular granzyme B as it is secreted by activated immune cells in the tumor microenvironment, which may highlight tumors that will regress on treatment with immunomodulatory therapies. The study population is focused on genitourinary malignancies, including renal cell and urothelial cancer, two tumor types with high mutational burden and tumor infiltrating lymphocytes compared to other tumor types, and have a predictable response rate at the population level to immune checkpoint inhibitors.

Official Title

A First-in-Human, Phase I/II PET Imaging Study of 64Cu-GRIP B, a Radiotracer Targeting Granzyme B, in Patients With Advanced Genitourinary Malignancies

Details

PRIMARY OBJECTIVES:

  1. Cohort A: To determine safety, dosimetry, and pharmacokinetics of 64Cu-GRIP B PET in patients with metastatic GU malignancy (renal, urothelial, or prostate)
  2. Cohort B and C: To determine the mean percent change in both tumor maximum standardized uptake value (SUVmax), and ratio of SUVmax/blood standardized uptake value average (SUVave) on 64Cu-GRIP B PET in patients with participants with metastatic renal cell carcinoma (RCC) and urothelial carcinoma (UC) (Cohort B) or metastatic castrate-resistant prostate cancer (mCRPC) (Cohort C).

SECONDARY OBJECTIVES:

  1. To determine the safety and average organ dosimetry of 64Cu-GRIP B PET in patients with participants with metastatic RCC and UC (Cohort B) or mCRPC (Cohort C).
  2. To descriptively report the patterns of intra-tumoral uptake of 64Cu-GRIP B on whole body PET, including by site of disease, uptake by tumor type, inter-tumoral and inter-patient heterogeneity, and tumor-to-background signal at baseline and at the time of progression (Cohorts B and C) in participants with metastatic RCC and UC (Cohort B) or mCRPC (Cohort C).
  3. To descriptively report Grade >= 2 immune-related adverse event(s) in patients with metastatic RCC and UC (Cohort B) who have 64Cu-GRIP B PET performed within 14 days of onset of event.
  4. To descriptively report the number of lesions identified on 64Cu-GRIP B PET compared with conventional imaging in patients with metastatic RCC and UC (Cohort B) or mCRPC (Cohort C).
  5. To determine whether baseline uptake on 64Cu-GRIP B PET is associated with subsequent clinical outcomes, including objective response, progression-free survival, response defined as decrease > 50% from baseline (PSA50), and immune-related adverse events (irAE) in participants with metastatic RCC and UC (Cohort B) or mCRPC (Cohort C).

OUTLINE:

A total of 6 participants will be enrolled in Cohort A, initially. Successful completion of the feasibility portion of the study (Cohort A) will provide the necessary preliminary data to support subsequent enrollment in Cohorts B and C. All participants will receive 64Cu-GRIP B PET at baseline. For participants in Cohorts B & C, another PET scan will be performed 8 weeks following initiation of checkpoint inhibitor treatment, and at disease progression. Participants will be followed for up to 2 years for longitudinal endpoints.

Keywords

Prostate Cancer, Renal Cancer, Urethral Cancer, Imaging Study, Radiotracer, Granzyme B, Kidney Neoplasms, Urethral Neoplasms, Copper, Copper-64 labeled Granzyme B (64Cu-GRIP B), Positron Emission Tomography (PET)

Eligibility

You can join if…

Open to people ages 18 years and up

  1. Disease characteristics by cohort, as defined by:

    Cohort A:

    • Histologically-confirmed metastatic solid tumor malignancy (3 Male, 3 Female)
    • Locally advanced or metastatic disease on conventional imaging

    Cohort B:

    Cohort C:

  2. Planned treatment with immune checkpoint inhibitor (Cohorts B and C only)
  3. Willing to undergo paired tumor biopsies and has safely accessible bone or soft tissue lesion (Cohorts B and C only)
  4. The subject is able and willing to comply with study procedures and provide signed and dated informed consent.
  5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  6. Age 18 years or older at the time of study entry.
  7. Adequate organ function, as defined by:
    • Serum creatinine <= 1.5 x upper limit of normal (ULN) or estimated creatinine clearance > 60 mL/min
    • Total bilirubin <= 1.5 x ULN (< 3 x ULN in patients with documented or suspected Gilbert's).
    • Hemoglobin >= 8.0 g/dL
    • Platelet count >= 75,000/microliter
    • Absolute neutrophil count ≥ 1000/microliter
  8. Patients must not be pregnant or breast feeding. Women of childbearing potential are required to obtain a negative pregnancy test within 14 days of PET Imaging scan. Effective contraception (men and women) must be used in subjects of child-bearing potential.

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. Is currently pregnant or breastfeeding.

Location

  • UCSF accepting new patients
    San Francisco California 94143 United States

Lead Scientist at UCSF

  • Rahul Aggarwal, MD
    I am a Medical Oncologist within the Division of Hematology/Oncology at the University of California San Francisco. My clinical practice focuses on patients with advanced solid tumor malignancies with a particular emphasis on genitourinary malignancies including prostate, kidney, bladder, and testicular cancer. I serve as the Co-Leader for the GU Medical Oncology program at UCSF.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Rahul Aggarwal
ID
NCT05888532
Phase
Phase 1/2 research study
Study Type
Interventional
Participants
Expecting 61 study participants
Last Updated
Contact us about this trial