Serial Ultrasound in Metastatic Renal Cell Carcinoma (mRCC)

Study Overview
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Brief Summary
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To assess whether changes in quantitative tumor perfusion parameters after 3 weeks of treatment, as measured by power doppler ultrasound, can predict initial objective response, defined by current standard-of-care, to therapy at 12 weeks after start of treatment

Official Title
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Early Therapeutic Monitoring of Response to Therapy With Serial Ultrasound in Metastatic Renal Cell Carcinoma (mRCC)

Conditions
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Kidney Cancer, Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma

Intervention / Treatment
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* Diagnostic Test: Doppler Ultrasound
* Device: Vantage 256 with C5-2v transducer
* Drug: Vascular Endothelial Growth Factor Receptor 2 tyrosine kinase inhibitor
* Other: non-ICI therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Pathology-confirmed diagnosis of metastatic RCC At least one tumor lesion greater than 1 cm in diameter, amenable to ultrasound imaging Written informed consent. Specific inclusion criteria: arm 1: planned to be treated with combination of VEGFR2 tyrosine kinase inhibitor (TKI) plus immune checkpoint inhibitor (ICI) arm 2: planned to be treated with non-ICI therapy Exclusion Criteria: -Any comorbid condition that, in the opinion of the treating provider or the Protocol Directors, compromises the participant's ability to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years

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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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tyrosine kinase (TKI) inhibitor plus immune checkpoint inhibitor (ICI)<br>Patients are planned to be treated with vascular endothelial growth factor 2 (VEGFR2) tyrosine kinase inhibitor (TKI) plus immune checkpoint inhibitor (ICI) | Diagnostic Test: Doppler Ultrasound<br>* Power doppler measurements will be made<br>Device: Vantage 256 with C5-2v transducer<br>* Vantage 256 with C5-2v transducer, used for power doppler ultrasound, manufactured by Verasonics<br>Drug: Vascular Endothelial Growth Factor Receptor 2 tyrosine kinase inhibitor<br>* Participants will receive less than 4 weeks of TKI treatment during the first 12 weeks<br>* Other names: TKI;|
| Experimental: Non-ICI therapy<br>Patients are planned to be treated with non-ICI therapy | Diagnostic Test: Doppler Ultrasound<br>* Power doppler measurements will be made<br>Device: Vantage 256 with C5-2v transducer<br>* Vantage 256 with C5-2v transducer, used for power doppler ultrasound, manufactured by Verasonics<br>Other: non-ICI therapy<br>* TKI monotherapy, combination of TKI with other kinase inhibitor, localized tumor therapy such as radiation, chemo- or radioembolization<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure Initial Objective response | Initial objective response is defined as having either Complete Response (CR) or Partial Response (PR) per RECIST v1.1 at first on-treatment response evaluation 8-16 weeks after initiating treatment. The results will be expressed as number without dispersion. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative change in tumor burden compared to baseline | Relative change will be assessed as sum of all tumor diameters between treatment 'baseline' and first on-treatment response evaluation 8-16 weeks after start of treatment, using RECIST v1.1 for tumor diameter measurements, expressed as mean +/- standard deviation and median with interquartile range | 12 weeks | 
| Lesion response compared to baseline | Relative change in tumor diameter of a single lesion between treatment 'baseline' and first on-treatment response evaluation 8-16 weeks after start of treatment, using RECIST v1.1 for tumor diameter measurements, will be measured as mean +/- standard deviation and median with interquartile range. | 12 weeks | 
| Progression free survival (PFS) | PFS is defined as not having experienced any progressive disease (PD) per RECIST v1.1 within the first 12 months after initiating treatment (day 1 will be treatment start date), as a number and proportion without dispersion. | 12 months |