Kidney Cancer, Metastatic Renal Cell Carcinoma, Renal Cell Carcinoma
Conditions
Brief summary
To assess whether changes in quantitative tumor perfusion parameters after 3 or 6 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
Interventions
DIAGNOSTIC_TESTDoppler Ultrasound
Power Doppler measurements will be made
DEVICESIEMENS S3000 and Verasonics Vantage 256
Vantage 256 used for power Doppler ultrasound, manufactured by Verasonics
DRUGStandard-of-care Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) tyrosine kinase inhibitor (TKI) plus immune checkpoint inhibitor (ICI)
Standard-of-care Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) tyrosine kinase inhibitor (TKI) plus immune checkpoint inhibitor (ICI).
DRUGStandard-of-care non-immune checkpoint inhibitor (ICI) such as single-agent VEGFR2 TKI
Standard-of-care non-immune checkpoint inhibitor (ICI) such as single-agent VEGFR2 TKI
Sponsors
National Institutes of Health (NIH)
Stanford University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older * Pathology-confirmed diagnosis of Renal cell carcinoma (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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Initial Objective Response- First Participation | 12 weeks | Initial objective response was 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. |
| Initial Objective Response- Second Participation | 12 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Initial Per-Lesion Response Compared To Baseline - First Participation | 12 weeks | The relative change in tumor diameter of a single lesion between treatment 'baseline' and the first on-treatment response evaluation 8-16 weeks after the start of treatment, using RECIST v1.1 for tumor diameter measurements. This was measured as percent change and reported as mean ± standard deviation. |
| Initial Per-Lesion Response Compared To Baseline - Second Participation | 12 weeks | The relative change in tumor diameter of a single lesion between treatment 'baseline' and the first on-treatment response evaluation 8-16 weeks after the start of treatment, using RECIST v1.1 for tumor diameter measurements. This was measured as percent change and reported as mean ± standard deviation. |
| Initial Relative Change in Tumor Burden Compared to Baseline - First Participation | 8-16 weeks after the start of treatment | Tumor burden was assessed as the sum of all tumor diameters at baseline compared to the first on-treatment response evaluation (8-16 weeks after the start of treatment) using RECIST v1.1 criteria |
| 12-month Progression Free Survival (PFS)- Second Participation | 12 months | 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-month Progression Free Survival (PFS)- First Participation | 12 months | PFS was 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). |
| Initial Relative Change in Tumor Burden Compared to Baseline - Second Participation | 8-16 weeks after the start of treatment | Tumor burden was assessed as the sum of all tumor diameters at baseline compared to the first on-treatment response evaluation (8-16 weeks after the start of treatment) using RECIST v1.1 criteria |
Countries
United States
Participant flow
Pre-assignment details
A total of 22 participants were enrolled in the study. Twelve participants started in Arm 1 and five participants started in Arm 2. Additional two participants consecutively participated in both arms; these participants are reported in Arm 3. Three participants were enrolled but did not start treatment and are not included in any arm.
Participants by arm
| Arm | Count |
|---|---|
| ARM 1: Tyrosine Kinase Inhibitor (TKI) Plus Immune Checkpoint Inhibitor (ICI) Patients are planned to be treated with vascular endothelial growth factor 2 (VEGFR2) tyrosine kinase inhibitor (TKI) plus immune checkpoint inhibitor (ICI)
Doppler Ultrasound: Power Doppler measurements will be made.
SIEMENS S3000 and Verasonics Vantage 256: Vantage 256 used for power Doppler ultrasound, manufactured by Verasonics. | 12 |
| ARM 2: Non-ICI Therapy Patients are planned to be treated with non-ICI therapy
Doppler Ultrasound: Power Doppler measurements will be made.
SIEMENS S3000 and Verasonics Vantage 256: Vantage 256 used for power Doppler ultrasound, manufactured by Verasonics. | 5 |
| ARM 3: Enrolled Consecutively in Both Arms Patients were enrolled consecutively in both arms. | 2 |
| Total | 19 |
Baseline characteristics
| Characteristic | ARM 1: Tyrosine Kinase Inhibitor (TKI) Plus Immune Checkpoint Inhibitor (ICI) | ARM 2: Non-ICI Therapy | ARM 3: Enrolled Consecutively in Both Arms | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 4 Participants | 0 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 1 Participants | 2 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 1 Participants | 2 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 4 Participants | 0 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 0 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) White | 6 Participants | 3 Participants | 1 Participants | 10 Participants |
| Region of Enrollment United States | 12 participants | 5 participants | 2 participants | 19 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 11 Participants | 4 Participants | 1 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 12 | 0 / 5 | 0 / 2 |
| other Total, other adverse events | 2 / 12 | 0 / 5 | 0 / 2 |
| serious Total, serious adverse events | 0 / 12 | 0 / 5 | 0 / 2 |
Outcome results
Primary
Initial Objective Response- First Participation
Initial objective response was 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.
Time frame: 12 weeks
Population: Two of fourteen participants in Arm 1 were not evaluable because they were removed from the study during active participation without undergoing any response evaluation.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ARM 1: Tyrosine Kinase Inhibitor (TKI) Plus Immune Checkpoint Inhibitor (ICI) | Initial Objective Response- First Participation | Yes (CR or PR) | 5 Participants |
| ARM 1: Tyrosine Kinase Inhibitor (TKI) Plus Immune Checkpoint Inhibitor (ICI) | Initial Objective Response- First Participation | No (SD or PD) | 7 Participants |
| ARM 2: Non-ICI Therapy | Initial Objective Response- First Participation | Yes (CR or PR) | 1 Participants |
| ARM 2: Non-ICI Therapy | Initial Objective Response- First Participation | No (SD or PD) | 4 Participants |
Primary
Initial Objective Response- Second Participation
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.
Time frame: 12 weeks
Population: This measure reflects outcome data from the second participation of two individuals enrolled in both Arm 1 and Arm 2. For their second participation, these individuals are grouped under Arm 3. Each participant is counted once in this outcome based on the second treatment period. For one of the two participants the outcome measure was not defined for their second treatment period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ARM 1: Tyrosine Kinase Inhibitor (TKI) Plus Immune Checkpoint Inhibitor (ICI) | Initial Objective Response- Second Participation | Yes (CR or PR) | 0 Participants |
| ARM 1: Tyrosine Kinase Inhibitor (TKI) Plus Immune Checkpoint Inhibitor (ICI) | Initial Objective Response- Second Participation | No (SD or PD) | 1 Participants |
Secondary
12-month Progression Free Survival (PFS)- First Participation
PFS was 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).
Time frame: 12 months
Population: Three of fourteen patients in arm 1 were not evaluable.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ARM 1: Tyrosine Kinase Inhibitor (TKI) Plus Immune Checkpoint Inhibitor (ICI) | 12-month Progression Free Survival (PFS)- First Participation | Yes (No PD and no death experienced) | 7 Participants |
| ARM 1: Tyrosine Kinase Inhibitor (TKI) Plus Immune Checkpoint Inhibitor (ICI) | 12-month Progression Free Survival (PFS)- First Participation | No (PD or death experienced) | 4 Participants |
| ARM 2: Non-ICI Therapy | 12-month Progression Free Survival (PFS)- First Participation | Yes (No PD and no death experienced) | 3 Participants |
| ARM 2: Non-ICI Therapy | 12-month Progression Free Survival (PFS)- First Participation | No (PD or death experienced) | 2 Participants |
Secondary
12-month Progression Free Survival (PFS)- Second Participation
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.
Time frame: 12 months
Population: This outcome measure reflects 12-month progression-free survival for two participants who enrolled a second time after initial treatment. These participants are grouped under Arm 3, and each is counted once based on survival status from their second participation. For one participant the outcome measure was not defined for their second participation.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ARM 1: Tyrosine Kinase Inhibitor (TKI) Plus Immune Checkpoint Inhibitor (ICI) | 12-month Progression Free Survival (PFS)- Second Participation | Yes (No PD and no death experienced) | 0 Participants |
| ARM 1: Tyrosine Kinase Inhibitor (TKI) Plus Immune Checkpoint Inhibitor (ICI) | 12-month Progression Free Survival (PFS)- Second Participation | No (PD or death experienced) | 1 Participants |
Secondary
Initial Per-Lesion Response Compared To Baseline - First Participation
The relative change in tumor diameter of a single lesion between treatment 'baseline' and the first on-treatment response evaluation 8-16 weeks after the start of treatment, using RECIST v1.1 for tumor diameter measurements. This was measured as percent change and reported as mean ± standard deviation.
Time frame: 12 weeks
Population: Two of fourteen participants in Arm 1 were not evaluable because they were removed from the study during active participation without undergoing any response evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ARM 1: Tyrosine Kinase Inhibitor (TKI) Plus Immune Checkpoint Inhibitor (ICI) | Initial Per-Lesion Response Compared To Baseline - First Participation | -28.0 Percentage change from baseline | Standard Deviation 23 |
| ARM 2: Non-ICI Therapy | Initial Per-Lesion Response Compared To Baseline - First Participation | -4.6 Percentage change from baseline | Standard Deviation 19 |
Secondary
Initial Per-Lesion Response Compared To Baseline - Second Participation
The relative change in tumor diameter of a single lesion between treatment 'baseline' and the first on-treatment response evaluation 8-16 weeks after the start of treatment, using RECIST v1.1 for tumor diameter measurements. This was measured as percent change and reported as mean ± standard deviation.
Time frame: 12 weeks
Population: The total number of participants analyzed for this outcome measure reflects only those who were evaluable. Two participants in Arm 1 were not evaluable because they were removed from the study during active participation without undergoing any response evaluation. One participant in Arm 3 received a treatment during the second participation, for which the outcome measure was not defined.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ARM 1: Tyrosine Kinase Inhibitor (TKI) Plus Immune Checkpoint Inhibitor (ICI) | Initial Per-Lesion Response Compared To Baseline - Second Participation | -6.3 Percentage change from baseline | Standard Deviation 18.7 |
Secondary
Initial Relative Change in Tumor Burden Compared to Baseline - First Participation
Tumor burden was assessed as the sum of all tumor diameters at baseline compared to the first on-treatment response evaluation (8-16 weeks after the start of treatment) using RECIST v1.1 criteria
Time frame: 8-16 weeks after the start of treatment
Population: Two of fourteen participants in Arm 1 were not evaluable because they were removed from the study during active participation without undergoing any response evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ARM 1: Tyrosine Kinase Inhibitor (TKI) Plus Immune Checkpoint Inhibitor (ICI) | Initial Relative Change in Tumor Burden Compared to Baseline - First Participation | -16.0 Percentage change from baseline | Standard Deviation 70.3 |
| ARM 2: Non-ICI Therapy | Initial Relative Change in Tumor Burden Compared to Baseline - First Participation | 43.7 Percentage change from baseline | Standard Deviation 94.8 |
Secondary
Initial Relative Change in Tumor Burden Compared to Baseline - Second Participation
Tumor burden was assessed as the sum of all tumor diameters at baseline compared to the first on-treatment response evaluation (8-16 weeks after the start of treatment) using RECIST v1.1 criteria
Time frame: 8-16 weeks after the start of treatment
Population: This measure reflects outcome data from the second participation of two individuals enrolled in both Arm 1 and Arm 2. For their second participation, these individuals are grouped under Arm 3. Each participant is counted once in this outcome based on the second treatment period. For one of the two participants the outcome measure was not defined for their second treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ARM 1: Tyrosine Kinase Inhibitor (TKI) Plus Immune Checkpoint Inhibitor (ICI) | Initial Relative Change in Tumor Burden Compared to Baseline - Second Participation | -20.7 Percentage change from baseline | Standard Deviation 0 |