Trial Comparing Stereotactic Body Radiation Therapy to Radiofrequency Ablation for Renal Cell Carcinoma

Study Overview
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Brief Summary
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This study will assess whether Stereotactic Body Radiation Therapy (SBRT) can provide comparable local control, with similar or improved toxicity rates compared to Radio Frequency Ablation (RFA) when treating small renal cell carcinomas.

Official Title
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A Phase II Randomized Trial Comparing Stereotactic Body Radiation Therapy to Radiofrequency Ablation for the Treatment of Localized Renal Cell Carcinoma (RCC)

Conditions
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Renal Cell Carcinoma

Intervention / Treatment
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* Radiation: SBRT
* Radiation: RFA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for SBRT vs. RFA Randomization: Patients with renal cell carcinoma less than 4 cm in maximum diameter, who are poor surgical candidates are eligible for randomization between SBRT and RFA (Renal cell carcinoma must be pathologically proven). The primary tumor must be in a location amendable to RFA within the kidney. Patients must be appropriate candidates for RFA, with platelets ≥50,000/mm3 and an international normalized ratio of 1.5. Patients must have an ECOG (a measurement of general well being and activities of daily living; scores range from 0 to 5 where 0 represents perfect health) score ≤ 3. There is no required minimum renal function (patients will be counseled about the possible need for dialysis, if applicable, just as would be the case for radical or partial nephrectomy). Patients must sign an informed consent form approved for this purpose by the Institutional Review Board (IRB) of the University of Michigan Medical Center indicating that they are aware of the investigational aspects of the treatment and the potential risks. Ability to understand and the willingness to sign a written informed consent. If a patient is randomized to the RFA arm, but is deemed not to be an anesthesia candidate, he/she will be placed in the non-randomized SBRT cohort. Inclusion Criteria for non-randomized SBRT arm: Patients with renal cell carcinoma less than 8 cm in maximum diameter, patients with metastatic RCC who require local palliation or are progressing through systemic disease, patients who are poor surgical candidates and have tumor location not amenable to RFA, or patients who would prefer a noninvasive means of treatment are eligible for the non-randomized SBRT cohort (Renal cell carcinoma must be pathologically proven). There are no limitations based on location of the primary tumor within the kidney. Patients must have an ECOG score ≤ 3. There is no required minimum renal function (patients will be counseled about the possible need for dialysis, if applicable, just as would be the case for radical or partial nephrectomy). Patients must sign an informed consent form approved for this purpose by the Institutional Review Board (IRB) of the University of Michigan Medical Center indicating that they are aware of the investigational aspects of the treatment and the potential risks. Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria: Patients younger than 18 or pregnant women.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Randomized SBRT<br>Patients who meet eligibility criteria (unilateral primary renal cell carcinoma less than 4 cm in greatest diameter) and are randomized to Stereotactic Body Radiation Therapy (SBRT) will receive SBRT delivered in fractions of 20 Gy, approximately every other day, for a total of three treatments. If the target is deemed too close to organs at risk, 5 fractions of up to 10 Gy per fraction will be prescribed. | Radiation: SBRT<br> <br> * Other names: Stereotactic Body Radiation Therapy;|
| Active Comparator: Randomized RFA<br>Patients who meet eligibility criteria (unilateral primary renal cell carcinoma less than 4 cm in greatest diameter) and are randomized to Radiofrequency Ablation (RFA) will receive RFA. | Radiation: RFA<br> <br> * Other names: Radiofrequency Ablation;|
| Active Comparator: Non-Randomized SBRT<br>Patients with renal cell carcinoma's greater than or equal to 4 cm in diameter, and up to 8 cm in diameter, may be placed in the non-randomized stereotactic body radiation therapy arm. Patients with tumors not amenable to RFA, those with metastatic disease, and those who elect a noninvasive means of treatment will also be eligible to receive treatment in the non-randomized SBRT cohort. | Radiation: SBRT<br> <br> * Other names: Stereotactic Body Radiation Therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With Local Control of Disease | On imaging, local control will be defined as when the treated lesion shows no enhancement. | 12 months | 
| Cumulative Incidence of Grade 2 and Greater Toxicities | The number of patients reporting grade 2 and greater toxicities (for this trial the Common Terminology Criteria for Adverse Events or CTCAE was used). | up to 30 days after the last study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in Quality of Life (QOL) Scores Between SBRT and RFA Treatment Arms | QOL scores will be summarized descriptively by treatment at each time point using the Convalescence and Recovery Evaluation (CARE) and SF-12 quality of life assessments . Any differences between treatment groups will be tested in the context of a general linear model with terms for treatment, time, treatment time and possibly other patient level covariates that might explain QOL. | Pre-study, last day of treatment; 1, 3, 6, 12, 18, 24 and 36 months post treatment | 
| Difference in Patient Time Away (Measured in Days) Between SBRT and RFA Treatment Arms | Patient time away from work/home secondary to treatment will be captured via patient questionnaire as a number of days and will be summarized descriptively by treatment group. Any differences between treatment groups will be tested by a two-sample t-test or nonparametric Mann-Whitney test. | Pre-study, last day of treatment; 1, 3, 6, 12, 18, 24 and 36 months post treatment | 
| Metastasis Free Survival Time |  | 36 months post treatment | 
| Overall Survival Time |  | 36 months post treatment | 
| Difference in Incidence of Treatment Related Pain Between SBRT and RFA Treatment Arms | All patients will be followed to assess the development of treatment related pain, and resultant usage of analgesics (drug classification and dosage) for treatment related pain. Incidence and severity of pain will be recorded for all patients, using the Common Terminology Criteria for Adverse Events (CTCAE), as will any resultant use of analgesics, and these will be compared between the two arms and analyzed in the non-randomized SBRT cohort. | Pre-study, last day of treatment; 1, 3, 6, 12, 18, 24 and 36 months post treatment |