Kidney Cancer Clinical Trial
64Cu-GRIP B in Patients With Advanced Malignancies
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.
Full Description
PRIMARY OBJECTIVES:
I. To determine the safety, dosimetry, and pharmacokinetics of 64Cu-GRIP B PET in patients with metastatic GU malignancy (renal, urothelial, or prostate) (3 males, 3 females). (Cohort A) II. To determine the mean percent change in both tumor maximum standardized uptake value (SUVmax) and ratio of SUVmax//blood average standardized uptake value (SUVave) on 64Cu-GRIP B PET in patients with participants with metastatic renal cell carcinoma (RCC) and urothelial carcinoma (UC) (Cohort B) or metastatic castration-resistant prostate cancer (mCRPC) (Cohort C).
SECONDARY OBJECTIVES:
I. To determine the safety and average organ dosimetry of 64Cu-GRIP B PET in patients with participants with metastatic RCC and UC (Cohort B), mCRPC (Cohort C) or other solid tumor malignancies (Cohort D).
II. 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 in patients with participants with metastatic RCC and UC (Cohort B), mCRPC (Cohort C), or other solid tumor malignancies (Cohort D).
III. To descriptively report PET at 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.
IV. To descriptively report the number of lesions identified on 64Cu-GRIP B PET compared with conventional imaging in patients with participants with metastatic RCC and UC (Cohort B), mCRPC (Cohort C), or other solid tumor malignancies (Cohort D).
V. To determine whether baseline uptake on 64Cu-GRIP B PET is associated with subsequent clinical outcomes including objective response, progression-free survival, prostate-specific antigen 50% reduction (PSA50) response, and immune-related adverse events in participants with metastatic RCC and UC (Cohort B), mCRPC (Cohort C), or other solid tumor malignancies (Cohort D).
OUTLINE: Patients are assigned to 1 of 4 cohorts:
Cohort A: Participants with metastatic GU malignancy (renal,urothelial, or prostate) Cohort B: Participants with metastatic renal cell carcinoma (RCC) or urothelial cancer (UC).
Cohort C: Participants with mCRPC Cohort D: Participants with solid tumor malignancies
All participants will receive 64Cu-GRIP B PET at baseline. For participants in Cohorts B and C, another PET scan will be performed 8 weeks and at disease progression. Participants in Cohort D will undergo PET/CT or PET/MRI throughout the study and may undergo an optional 64Cu-GRIP B PET at the time of progression. Safety monitoring includes adverse event assessment at screening, 60 minutes (+/- 15 min), 2 hours (+/- 30 min), and 24 hours (+/- 4 hours) following 64Cu-GRIP B injections. Participants will be followed for up to 2 years for longitudinal endpoints.
Eligibility Criteria
Inclusion Criteria:
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:
Histologically-confirmed metastatic renal cell carcinoma (any histologic sub-type) or urothelial carcinoma
Locally advanced or metastatic disease on conventional imaging
Cohort C:
Histologically-confirmed prostate adenocarcinoma
Metastatic castration resistant prostate cancer by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria
Planned treatment with immune checkpoint inhibitor (Cohorts B and C only)
Willing to undergo paired tumor biopsies and has safely accessible bone or soft tissue lesion (Cohorts B and C only)
The subject is able and willing to comply with study procedures and provide signed and dated informed consent.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
Age 18 years or older at the time of study entry.
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
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.
Exclusion Criteria:
Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent.
Any condition that, in the opinion of the Principal Investigator, would impair the patient's ability to comply with study procedures.
Is currently pregnant or breastfeeding.
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There is 1 Location for this study
San Francisco California, 94143, United States More Info
Principal Investigator
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