Trial Outcomes & Findings for Functional Microscale Organotypic Assays to Predict Patient Response to Anti-Angiogenesis Therapies (NCT NCT03387514)

Last Updated: 2022-12-21

Results Overview

Tumor FDG PET SUV data is provided from baseline PET tumor data. Participants with baseline 18F-DCFPyL PSMA PET/CT prior to surgical nephrectomy and metastatic disease sampling were analyzed based single timepoints for PET SUVmax values of tumor uptake (primary and metastatic disease)

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

5 participants

Primary outcome timeframe

Baseline

Results posted on

2022-12-21

Participant Flow

Participants were recruited from the University of Wisconsin Carbone Cancer Center from December 2018 to June 2021.

Participant milestones

Participant milestones
Measure	18F-DCFPyL Whole Body PET/CT Scan PSMA-based 18F-DCFPyL PET tracer for PET/CT exams administered at the following timepoints: PET1 - Prior to scheduled nephrectomy PET2 - to establish a new baseline PET before systemic therapy * PET2A - Post-surgery and prior to start of standard of care systemic therapy * PET2B - 12-16 weeks from start of first line systemic therapy (immune-based or anti-angiogenic) PET3 - If first line systemic therapy did not include anti-angiogenesis therapy and new systemic therapy does include anti-angiogenesis therapy * PET3A - Prior to start of additional anti-angiogenesis therapy * PET3B - 12-16 weeks from the start of additional anti-angiogenesis therapy PET4 - obtained at clinical progression or 2 years following initial systemic therapy
Overall Study STARTED	5
Overall Study PET 1	5
Overall Study Tissue Samples	4
Overall Study PET 2A	0
Overall Study PET 2B	0
Overall Study PET 3A	0
Overall Study PET 3B	0
Overall Study PET 4	0
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	18F-DCFPyL Whole Body PET/CT Scan PSMA-based 18F-DCFPyL PET tracer for PET/CT exams administered at the following timepoints: PET1 - Prior to scheduled nephrectomy PET2 - to establish a new baseline PET before systemic therapy * PET2A - Post-surgery and prior to start of standard of care systemic therapy * PET2B - 12-16 weeks from start of first line systemic therapy (immune-based or anti-angiogenic) PET3 - If first line systemic therapy did not include anti-angiogenesis therapy and new systemic therapy does include anti-angiogenesis therapy * PET3A - Prior to start of additional anti-angiogenesis therapy * PET3B - 12-16 weeks from the start of additional anti-angiogenesis therapy PET4 - obtained at clinical progression or 2 years following initial systemic therapy
Overall Study Withdrawal by Subject	2
Overall Study Physician Decision	1
Overall Study Lost to Follow-up	2

Baseline Characteristics

Functional Microscale Organotypic Assays to Predict Patient Response to Anti-Angiogenesis Therapies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	18F-DCFPyL Whole Body PET/CT Scan n=5 Participants PSMA-based 18F-DCFPyL PET tracer for PET/CT exams administered at the following timepoints: PET1 - Prior to scheduled nephrectomy PET2 - to establish a new baseline PET before systemic therapy * PET2A - Post-surgery and prior to start of standard of care systemic therapy * PET2B - 12-16 weeks from start of first line systemic therapy (immune-based or anti-angiogenic) PET3 - If first line systemic therapy did not include anti-angiogenesis therapy and new systemic therapy does include anti-angiogenesis therapy * PET3A - Prior to start of additional anti-angiogenesis therapy * PET3B - 12-16 weeks from the start of additional anti-angiogenesis therapy PET4 - obtained at clinical progression or 2 years following initial systemic therapy
Age, Customized 30-39 years	1 Participants n=5 Participants
Age, Customized 40-49 years	0 Participants n=5 Participants
Age, Customized 50-59 years	1 Participants n=5 Participants
Age, Customized 60-69 years	2 Participants n=5 Participants
Age, Customized 70-79 years	1 Participants n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	5 participants n=5 Participants
PET maximum SUV (SUVmax)	6.60 SUV STANDARD_DEVIATION 3.16 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline

Population: Five patients with baseline 18F-DCFPyL PSMA PET/CT prior to surgical nephrectomy and metastatic disease sampling were analyzed based on limited sample size and single timepoints for PET SUVmax values of tumor uptake (primary and metastatic disease).

Outcome measures

Outcome measures
Measure	18F-DCFPyL PET/CT Scan - Primary n=5 Participants Primary Renal Tumor	18F-DCFPyL PET/CT Scan - Metastases n=5 Participants Metastatic Lesions	18F-DCFPyL PET/CT Scan - Bone Metastases n=5 Participants Bone Metastases	18F-DCFPyL PET/CT Scan - Soft Tissue Metastases n=5 Participants Soft tissue metastases
Baseline Tumor FDG PET SUV Data by Disease Type at Baseline	8.78 SUV Standard Deviation 3.35	5.51 SUV Standard Deviation 2.56	7.57 SUV Standard Deviation 3.43	4.63 SUV Standard Deviation 1.70

PRIMARY outcome

Timeframe: Up to 24 months

Population: Data were not collected for Immunohistochemical PSMA staining due to termination of funding for this study due to low accrual (see section on limitation and caveats).

Compare PSMA imaging to histopathological endpoints which include tumor vascular density, immunohistochemical staining for PSMA and neovascularization (CD105, CD31 markers)

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to 24 months

Population: Data were not collected for Tumor vascular density due to termination of funding for this study due to low accrual (see section on limitation and caveats).

Compare PSMA imaging to histopathological endpoints which include tumor vascular density, immunohistochemical staining for PSMA and neovascularization (CD105, CD31 markers)

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to 24 months

Population: Data were not collected for CD105 and CD31 neovascularization due to termination of funding for this study due to low accrual (see section on limitation and caveats).

Compare PSMA imaging to histopathological endpoints which include tumor vascular density, immunohistochemical staining for PSMA and neovascularization (CD105, CD31 markers)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 24 months

Population: Patient tumor specimen were processed and positively selected for CD31 cells, for endothelial and epithelial cell fractions. Microphysiological models were established using the two cell populations using a mold casting strategy. Models were treated with therapeutic agents after 24 hr in culture and incubated with the agent for 72hr. Imaging with confocal microscopy was used to determine individual sprout numbers. Values were acquired from at least 2 independent experiments.

Patient-derived uVESSEL models (from primary \& metastatic sites) and incorporating patient-derived immune cells, will be tested for response to anti-angiogenic therapies including pazopanib, sunitinib, cabozantinib, and axitinib. Response will be quantified via multiple endpoints, e.g. vessel sprouting, PSMA expression, cell death.

Outcome measures

Outcome measures
Measure	18F-DCFPyL PET/CT Scan - Primary n=1 Participants Primary Renal Tumor	18F-DCFPyL PET/CT Scan - Metastases n=1 Participants Metastatic Lesions	18F-DCFPyL PET/CT Scan - Bone Metastases Bone Metastases	18F-DCFPyL PET/CT Scan - Soft Tissue Metastases Soft tissue metastases
Measure Therapy Response of Patient Specific uVESSEL (a Micro Scale Organotypic Co-culture Model): Vessel Sprouting Vehicle Control	4.333 Sprout number Standard Error 1.211	5.364 Sprout number Standard Error 0.927	—	—
Measure Therapy Response of Patient Specific uVESSEL (a Micro Scale Organotypic Co-culture Model): Vessel Sprouting Sunitinib	2.000 Sprout number Standard Error 1.155	13.330 Sprout number Standard Error 2.369	—	—
Measure Therapy Response of Patient Specific uVESSEL (a Micro Scale Organotypic Co-culture Model): Vessel Sprouting Pazopanib	2.400 Sprout number Standard Error 1.140	15.330 Sprout number Standard Error 3.964	—	—
Measure Therapy Response of Patient Specific uVESSEL (a Micro Scale Organotypic Co-culture Model): Vessel Sprouting Cabozantinib	3.333 Sprout number Standard Error 0.333	21.300 Sprout number Standard Error 3.512	—	—
Measure Therapy Response of Patient Specific uVESSEL (a Micro Scale Organotypic Co-culture Model): Vessel Sprouting Axitinib	NA Sprout number Standard Error NA Not tested	NA Sprout number Standard Error NA Not Tested	—	—

SECONDARY outcome

Timeframe: Up to 24 months

Population: Data were not collected to evaluate the predictive power and validation of the uVESSEL model due to termination of funding for this study due to low accrual (see section on limitation and caveats).

Using the clinical, pathological and imaging endpoints, predictive models will e developed using responses to uVESSEL model above. More specifically the objective response (dichotomous endpoint of yes or no) measured using PSMA-based PET/CT will be used as a dependent variable in a logistic regression model with response to uVESSEL model from above as an independent predictor to segregate uVESSEL responses into two groups corresponding to responders and non-responders to anti-angiogenic therapies.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 24 months

Population: Data were not collected due to termination of funding for this study due to low accrual (see section on limitation and caveats).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 24 months

Population: A version of the models without endothelial cells was generated to evaluate tumor (only) response to therapeutics. To this end, a luminescent reagent was used to assess the amount of ATP in the models, which can be correlated to the number of live cells in the model. Measurements were taken at day 0 and at day 4 (after 72h of treatment) and normalized to account for patient-specific ATP variations. Values were acquired from at least 2 independent experiments.

Outcome measures

Outcome measures
Measure	18F-DCFPyL PET/CT Scan - Primary n=1 Participants Primary Renal Tumor	18F-DCFPyL PET/CT Scan - Metastases n=1 Participants Metastatic Lesions	18F-DCFPyL PET/CT Scan - Bone Metastases Bone Metastases	18F-DCFPyL PET/CT Scan - Soft Tissue Metastases Soft tissue metastases
Measure Therapy Response of Patient Specific uVESSEL (a Micro Scale Organotypic Co-culture Model): Cell Death Vehicle Control	148.8 Sprout number Standard Error 6.838	70.67 Sprout number Standard Error 3.23	—	—
Measure Therapy Response of Patient Specific uVESSEL (a Micro Scale Organotypic Co-culture Model): Cell Death Sunitinib	28.98 Sprout number Standard Error 4.86	38.38 Sprout number Standard Error 2.06	—	—
Measure Therapy Response of Patient Specific uVESSEL (a Micro Scale Organotypic Co-culture Model): Cell Death Pazopanib	94.74 Sprout number Standard Error 1.62	89.46 Sprout number Standard Error 2.57	—	—
Measure Therapy Response of Patient Specific uVESSEL (a Micro Scale Organotypic Co-culture Model): Cell Death Cabozantinib	54.05 Sprout number Standard Error 1.23	110.40 Sprout number Standard Error 7.05	—	—

Adverse Events

18F-DCFPyL Whole Body PET/CT Scan

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Steve Cho, MD

UW School of Medicine and Public Health

Phone: 608-263-5585

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place