Analysis of Primary and Metastatic Tumors in Patients With Renal Cell Carcinoma and Urothelial Carcinoma

Study Overview
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Brief Summary
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This is a comparative study using resected/ biopsied tumors samples collected from renal cell carcinoma and urothelial carcinoma patients who underwent surgical removal of lesions, followed by immune checkpoint blockade (ICB) treatment targting programmed cell death 1 (PD1) but developed new lesions later were also removed and stored in the biosample repository (BSR). The histology and genomic analysis of the pre-treatment and metastatic samples from the same patient would be used to find out the changes that may have lead to metastasis. Also, metastatic samples from ICB naive patients would be collected and compared with those from ICB treated patients to find out if the metastasis in treated patients was due to development of reistance.

Official Title
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Defining the Genomic and Histologic Landscape of Primary and Metastatic Tumors With Divergent Kinetics in Patients With Renal Cell Carcinoma (RCC) and Urothelial Carcinoma (UC) Treated With Immune Checkpoint Blockade (ICB)

Conditions
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Renal Cell Carcinoma, Urothelial Carcinoma, Bladder Cancer, Ureter Cancer, Urethral Cancer

Intervention / Treatment
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* Biological: Immune checkpoint inhibitor targeting PD1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible patients will include retrospectively identified patients with RCC or UC who have received treatment with ICB and achieved clinical benefit but subsequently developed a solitary new/progressive lesion that was removed surgically. Patients with other tumor types who otherwise meet criteria may be included at a later time Additionally, a group of patients with RCC who have undergone a metastasectomy but who did not receive treatment with ICB will be identified. These patients may be approached for study participation to serve as a comparator group Exclusion Criteria: -
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients treated with immune check point blocker<br>Patients who were treated with immune checkpoint inhibitor targeting PD1 and developed metastatic lesion later | Biological: Immune checkpoint inhibitor targeting PD1<br>* RCC and UC patients treated with immune checkpoint blockade<br>|
| Patients treated with targeted/ observational therapy<br>Patients who were not treated with immune checkpoint inhihibitor and developed metastatic lesion following other targeted therapy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histopathological characterization of samples from ICB treated patients | To characterize differences in histopathology and patterns of genomic expression between baseline tumors and metastases exhibiting divergent growth kinetics (escape metastases) in patients treated with immune checkpoint blockade (ICB) | 18 months | 
| Genomic characterization of samples from ICB treated patients | To characterize expression of different genes between baseline tumors and metastases exhibiting divergent growth kinetics (escape metastases) in patients treated with immune checkpoint blockade (ICB) | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histopathological characterization of samples from patients treated with targeted or observational therapy | To characterize differences in histopathology between baseline tumors and metastases in patients with RCC treated with observation or targeted therapy. | 18 months | 
| Comparison of Histopathological characteristics of metastatic samples from ICB naive and treated patients | To characterize differences in histopathology and patterns of genomic expression between escape metastases in patients treated with ICB from patients treated with targeted therapy or observation. | 18 months | 
| Genomic characterization of samples from patients treated with targeted or observational therapy | To characterize differences in patterns of genomic expression between baseline tumors and metastases in patients with RCC treated with observation or targeted therapy | 18 months | 
| Comparison of genomic characteristics of metastatic samples from ICB naive and treated patients | To characterize differences in patterns of genomic expression between escape metastases in patients treated with ICB from patients treated with targeted therapy or observation. | 18 months |