Serial Ultrasound of Solid Tumor Lesions to Detect Early Response to Cancer Immunotherapy

Study Overview
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Brief Summary
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Primary objective is to assess whether changes in quantitative tumor perfusion parameters after 3 weeks of treatment, as measured by CEUS, can predict initial objective response to therapy, defined by current standard-of-care Secondary objectives are to evaluate if there is an optimal ultrasound imaging modality (CEUS or conventional power Doppler or LEAD ultrasound) or optimal time point to predict initial objective response and to assess the correlation of tumor perfusion parameters with change in overall tumor burden, change in diameter on a per-lesion basis, and with 12-month progression-free survival (PFS).

Official Title
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Serial Ultrasound of Solid Tumor Lesions to Detect Early Response to Cancer Immunotherapy

Conditions
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Solid Tumor

Intervention / Treatment
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* Diagnostic Test: Doppler ultrasound
* Diagnostic Test: Long Ensemble Angular-coherence Doppler [LEAD] ultrasound
* Diagnostic Test: Contrast-enhanced ultrasound (CEUS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older pathology-confirmed diagnosis of cancer at least one solid tumor lesion greater than 1 cm in diameter (primary tumor and/or at metastatic site), amenable to ultrasound imaging planned to be treated with ipilimumab plus nivolumab or other ICI therapy written informed consent Exclusion Criteria: known hypersensitivity to sulfur hexafluoride lipid microsphere or its components, such as polyethylene glycol (PEG) 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ultrasound<br>Patients receiving standard of care immune checkpoint inhibitor are followed with the ultrasound studies at treatment baseline, 3 weeks and 6 weeks. | Diagnostic Test: Doppler ultrasound<br>* Power doppler measurements will be made using a portable Siemens S2000 ultrasound scanner<br>Diagnostic Test: Long Ensemble Angular-coherence Doppler [LEAD] ultrasound<br>* Long Ensemble Angular-coherence Doppler measurements will be made using a Verasonics Vantage 256 scanner with a C5-2v<br>Diagnostic Test: Contrast-enhanced ultrasound (CEUS)<br>* Contrast-enhanced ultrasound measurements will be made using Lumason IV contrast injection followed by an injection of normal saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Initial objective response per RECIST v1.1 | Initial objective response is defined as having either Complete Response (CR) or Partial Response (PR) per RECIST v1.1 | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Initial relative change in tumor burden | defined as relative change in the sum of diameters of all measurable tumors, assessed between treatment 'baseline' and first on-treatment response evaluation | 16 weeks | 
| Initial lesion response | defined as the relative change in tumor diameter of a single lesion between treatment 'baseline' and first on-treatment response evaluation | 16 weeks | 
| progression-free survival (PFS) | defined as not having experienced any PD per RECIST v1.1 | 12 months |