Carcinoma, Renal Cell
Conditions
Brief summary
The specific aims of this study are: 1. To determine the safety and feasibility of treating patients with a combination of MRI guided stereotactic body radiation therapy and microwave ablation. 2. To assess short and long-term toxicity rates of patients treated with a combined modality approach. 3. To assess local control, survival, and pathologic response to treatment
Detailed description
Renal cell carcinoma is traditionally managed via a surgical approach. Increasingly, local therapy with radiofrequency and microwave ablation is being utilized as an alternative for patients who may not tolerate a nephrectomy or who refuse one. Although local control rates for small lesions are excellent, they drop off precipitously for lesions over 4 cm. Furthermore, lesions in critical areas such as the renal hilum may be difficult to treat with this method. Stereotactic body radiation therapy (SBRT) has had a long record of treating patients with inoperable tumors in locations such as the lung and central nervous system, and there is increasing evidence that it may be useful for patients with renal cell carcinoma. The recent emergence of MRI-guided radiation therapy allows for direct visualization of tumors during treatment, and may potentially allow clinicians to treat tumors more precisely. This phase I study will treat renal cell carcinoma patients using a combination of MRI-guided stereotactic body radiation therapy and microwave ablation.
Interventions
RADIATIONStereotactic Body Radiation Therapy (SBRT)
Patients will be treated on study with a course of SBRT treatment by a radiation oncologist. Three SBRT dose levels targeting the primary tumor will be evaluated; level I: 6 Gy x 5 fractions (a common palliative dose), level II: 8 Gy x 5 fractions, and level III: 10 Gy x 5 fractions (a common definitive dose).
PROCEDUREMicrowave Ablation (MWA)
Performed under sedation using ultrasound and computed tomography (CT) guidance for percutaneous antenna placement and confirmation. Depending on size and location of tumor, one to three antennas (Certus 140; NeuWave Medical) will be used. The system is an FDA-approved, high-powered third-generation MW device that uses CO2 gas cooling to prevent shaft heating. The gas cooling allows the probes to be stuck into tissue by creating a small ice ball at the tip using the Joule-Thomson method, similar to the tissue cooling mechanism of cryoablation systems. Probes are 17-gauge, and various ablation zone configurations are available depending on the probe selected. An ablation protocol using the 65W power setting for 5 minutes will be used for most patients. Ultrasound will be used for real-time monitoring of the extent of ablation to achieve a 5mm margin beyond tumor, and immediate post-procedure imaging performed using contrast-enhanced CT (CECT) for patients with adequate renal functions.
Sponsors
University of Wisconsin, Madison
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with imaging findings consistent with renal cell carcinoma * Deemed medically inoperable per urology evaluation * Tumor size \>4cm in largest dimension * ECOG performance status of \<2 * Signed informed consent document(s) * Patients with metastatic disease will not be excluded
Exclusion criteria
* Patients who fail MRI screening * Pregnant or nursing women * History of prior radiation therapy to the upper abdomen * History of invasive cancer in the last 3 years (except for appropriately treated low-rist prostate cancer, treated non-melanoma/melanoma skin cancer, appropriately treated ductal carcinoma in situ or early stage invasive carcinoma of breast and appropriately treated in-situ/early stage cervical/endometrial cancer) * Treatment with a non-approved or investigational drug within 28 days of study treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting Toxicity With SBRT Combined With Microwave Ablation for Renal Cell Carcinoma | Until 30 days after ablation (up to 12 weeks on study) | Dose-limiting toxicity (DLT) will be defined as grade 4 or higher non-hematologic toxicity attributable to treatment. This will exclude toxicities not caused by treatment, such as pain due to tumor progression. Toxicities will be defined per NCI CTCAE v5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Local Control Rate Per RECIST Criteria as Reported by Count of Participants | 8 weeks | Radiologic response per RECIST criteria and volumetric measurements. |
| Progression Free Survival | 8 weeks | — |
| Overall Survival | 8 weeks | — |
| Tumor Pathology of Post-SBRT Specimen (H&E Staining) | 8 weeks | H&E staining for percentage of viable tumor remaining as measured by the presence of necrosis, fibrosis, hyalinization, and/or calcification, compared to pre-SBRT pathology |
Other
| Measure | Time frame | Description |
|---|---|---|
| Tumor Pathology of Post-SBRT Specimen (Pathologic Evaluation) | 8 weeks | Pathologic evaluation for percentage of viable tumor remaining as measured by the presence of necrosis, fibrosis, hyalinization, and/or calcification, compared to pre-SBRT pathology |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled from June 2018 to September 2022.
Participants by arm
| Arm | Count |
|---|---|
| Radiotherapy & Microwave Ablation 3+3 dose-escalation wherein three dose levels of stereotactic body radiation therapy (SBRT) would be evaluated:
1. Dose level I: 6 Gy x 5 fractions
2. Dose level II: 8 Gy x 5 fractions
3. Dose level III: 10 Gy x 5 fractions
Radiation treatments will be delivered two to three times a week, with five fractions completed over two weeks.
Four to six weeks after radiation treatment, patients will undergo repeat CT or MRI imaging to assess tumor response and suitability for microwave ablations.
Eight weeks after the conclusion of SBRT, patients will undergo microwave ablation (approximately 12 weeks after registration). | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Radiotherapy & Microwave Ablation |
|---|---|
| Age, Customized 70-79 years old | 2 Participants |
| Age, Customized 80-89 years old | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 2 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Dose-limiting Toxicity With SBRT Combined With Microwave Ablation for Renal Cell Carcinoma
Dose-limiting toxicity (DLT) will be defined as grade 4 or higher non-hematologic toxicity attributable to treatment. This will exclude toxicities not caused by treatment, such as pain due to tumor progression. Toxicities will be defined per NCI CTCAE v5.0.
Time frame: Until 30 days after ablation (up to 12 weeks on study)
Population: 1 participant did not undergo ablation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radiotherapy & Microwave Ablation | Dose-limiting Toxicity With SBRT Combined With Microwave Ablation for Renal Cell Carcinoma | 0 dose limiting toxicities |
Secondary
Local Control Rate Per RECIST Criteria as Reported by Count of Participants
Radiologic response per RECIST criteria and volumetric measurements.
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiotherapy & Microwave Ablation | Local Control Rate Per RECIST Criteria as Reported by Count of Participants | 2 Participants |
Secondary
Overall Survival
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiotherapy & Microwave Ablation | Overall Survival | 2 Participants |
Secondary
Progression Free Survival
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiotherapy & Microwave Ablation | Progression Free Survival | 2 Participants |
Secondary
Tumor Pathology of Post-SBRT Specimen (H&E Staining)
H&E staining for percentage of viable tumor remaining as measured by the presence of necrosis, fibrosis, hyalinization, and/or calcification, compared to pre-SBRT pathology
Time frame: 8 weeks
Population: tumor pathology was not analyzed as study was terminated early, no data collected
Other Pre-specified
Tumor Pathology of Post-SBRT Specimen (Pathologic Evaluation)
Pathologic evaluation for percentage of viable tumor remaining as measured by the presence of necrosis, fibrosis, hyalinization, and/or calcification, compared to pre-SBRT pathology
Time frame: 8 weeks