64Cu-GRIP B in Patients With Advanced Malignancies
Status
RECRUITING
Phase
PHASE1, PHASE2
Age
≥ 18 Years
Enrollments
91Conditions
Prostate Cancer, Renal Cancer, Urethral Cancer, Advanced Solid Tumor, Metastatic Castration-resistant Prostate Cancer, Solid Tumor, AdultDrugs
Copper-64 labeled Granzyme B (64Cu-GRIP B)Summary
This phase I/II clinical trial evaluates if using a radiotracer targeting granzyme B, 64-copper granzyme targeting restricted interaction peptide specific to family member B (64 Cu-GRIP B) with positron emission tomography (PET) imaging can be safe and useful for detecting granzyme B (GrB) in patients with advanced cancers that has spread to nearby tissue or lymph nodes (advanced). Granzyme B (GrB) is a biomarker produced by immune cells in response to immunotherapy, which may highlight tumors that are more likely to respond to treatment. The study population is focused on genitourinary (GU) 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. The information gained from this trial may allow researchers to develop future trials where 64Cu-GRIP B PET may serve as a biomarker to monitor early response to immunomodulatory therapies which are used to stimulate or suppress the immune system and may help the body fight cancer.
Detailed 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.
Locations
1 location Found with status Recruiting
Status
- RECRUITING
Contact Person
- Khadija Siddiqua
- 310-794-7329
- [email protected]
Principal Investigator
- Rahul Aggarwal, MD
Eligibility Criteria
Inclusion Criteria:
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:
* 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
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.
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. Is currently pregnant or breastfeeding.
Study Plan
Cohort A: 64Cu-GRIP B, Metastatic GU malignancies
EXPERIMENTAL
Participants with metastatic GU malignancy (renal, urothelial, or prostate) (3 males, 3 females), dosimetry calculation will be performed by obtaining whole body (vertex to thighs) PET images up to five time points from 0.5 to 24 hours post 64Cu-GRIP B injections. An additional intravenous line will be placed in the contra-lateral arm to collect blood for this group.
DRUG:
Copper-64 labeled Granzyme B (64Cu-GRIP B)Description:
Given IV prior to imagingPROCEDURE:
Positron Emission Tomography (PET)Description:
Imaging procedure
Cohort B: 64Cu-GRIP B, RCC and UC participants
EXPERIMENTAL
Participants with renal cell and urothelial carcinoma will have longitudinal imaging performed prior to treatment outside of this study with anti-programmed death-1 (PD-1)/anti-PD-1 ligand 1 (PD-L1) blockade (with or without concomitant anti-CTLA4 treatment), after 8 weeks of checkpoint blockade, and again at the time of disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
DRUG:
Copper-64 labeled Granzyme B (64Cu-GRIP B)Description:
Given IV prior to imagingPROCEDURE:
Positron Emission Tomography (PET)Description:
Imaging procedure
Cohort C: 64Cu-GRIP B, mCRPC participants
EXPERIMENTAL
Participants with metastatic castration resistant prostate cancer (mCRPC)) will have longitudinal imaging performed prior to treatment outside of this study, 8 weeks following initiation of treatment outside of this study, and at the time of disease progression by Prostate Cancer Working Group 3 (PCWG3) criteria.
DRUG:
Copper-64 labeled Granzyme B (64Cu-GRIP B)Description:
Given IV prior to imagingPROCEDURE:
Positron Emission Tomography (PET)Description:
Imaging procedure
Cohort D: 64Cu-GRIP B, Advanced malignancies
EXPERIMENTAL
participants with solid tumor malignancies will have longitudinal imaging performed prior to treatment outside of this study, 8 weeks following initiation of treatment, and the opportunity to have an optional scan at the time of progression.
DRUG:
Copper-64 labeled Granzyme B (64Cu-GRIP B)Description:
Given IV prior to imagingPROCEDURE:
Positron Emission Tomography (PET)Description:
Imaging procedure
Outcome Measures
Primary Outcome Measures
Frequency of treatment-emergent adverse events (Cohort A)
Percent of injected activity (Cohort A)
Time to maximum observed concentration (Tmax) (Cohort A)
Maximum observed concentration (Cmax) (Cohort A)
Area under the concentration-time curve (AUC) (Cohort A)
AUC extrapolated to infinity (Cohort A)
Median clearance (Cohort A)
Apparent terminal elimination rate constant (Cohort A)
Apparent terminal elimination half-life (Cohort A)
Change in SUVmax (Cohorts B, C, and D)
Change in SUVmax/SUVave (Cohorts B, C, and D)
Secondary Outcome Measures
Frequency of treatment-emergent adverse events (Cohorts B, C, and D)
Mean SUVmax in metastatic lesions by disease site (Cohorts B, C and D)
Percent of lesions detected for metastatic participants (Cohorts B, C and D)
Median change in SUVmax from baseline with reported immune-related adverse event (Cohort B)
Median change in SUVmax-ave from baseline with reported immune-related adverse event (Cohorts B)
Association of baseline uptake with object response (ORR) (Cohorts B, C and D)
Association of baseline uptake with progression-free survival (PFS) (Cohorts B, C and D)
Association of baseline uptake with reported PSA50 response (Cohort C)
Association of baseline uptake with reported immune-related adverse events (irAEs)(Cohorts B, C and D)
Timeline
Last Updated
December 22, 2023Start Date
June 5, 2023Today
January 16, 2025Completion Date ( Estimated )
January 31, 2027
Sponsors of this trial
Lead Sponsor
Rahul AggarwalCollaborating Sponsors
National Cancer Institute (NCI), U.S. Army Medical Research Acquisition Activity
RECRUITING 
21 - 64 Years