Stereotactic Body Radiation Therapy in Treating Patients With Oligometastatic Renal Cell Carcinoma

Study Overview
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Brief Summary
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This trial studies how well stereotactic body radiation therapy works in treating patients with kidney cancer that has spread to other places in the body. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the feasibility of incorporating stereotactic body radiation therapy (SBRT) as a component of definitive local treatment for oligometastatic renal cell carcinoma (RCC). II. To estimate the 12-month progression free survival (PFS) rate after study enrollment utilizing a strategy of definitive local treatment to all sites of disease in oligometastatic RCC as measured by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). SECONDARY OBJECTIVES: I. To determine the effect of SBRT on cellular replication, measured by ki-67 staining. II. To determine the systemic therapy free survival at 12 months. III. To estimate the overall survival at 12 months after study enrollment. IV. To estimate the freedom from new lesion development at 12 months. V. To determine the treatment related toxicities associated with SBRT as part of definitive local therapy for oligometastatic RCC. OUTLINE: Patients undergo SBRT over 1 day to 3 weeks based on the judgment of the treating radiation oncologist. After completion of study treatment, patients are followed up at 6 and 12 weeks, and then every 18 weeks for 1 year.

Official Title
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Feasibility Study of Stereotactic Body Radiation Therapy for Oligometastatic Renal Cell Carcinoma

Conditions
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Malignant Neoplasms of Urinary Tract, Oligometastatic Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma, Stage IV Renal Cell Cancer AJCC v8

Intervention / Treatment
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* Radiation: Stereotactic Body Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Oligometastatic RCC patients (less than or equal to 5 sites of metastases at the time of study entry). Pathologically confirmed diagnosis of RCC of any histology. At least one site which in the opinion of the treating radiation oncologist is treatable with SBRT and can be biopsied. Be willing and able to undergo biopsy of a lesion planned for SBRT both post treatment and pretreatment. In the event that a lesion amenable to SBRT was biopsied prior to enrollment, this material can be used in lieu of a planned biopsy if the tissue is available for review and ki-67 staining at MD Anderson. Be greater than or equal to 18 years of age on the day of signing informed consent. NOTE: Patients may be allowed on this trial without a biopsy if they are deemed medically unfit for biopsy or if the biopsy poses undue risk in the opinion of the treating physician(s). Eastern Cooperative Oncology Group (ECOG) performance status 0-2. NOTE: If subject is unable to walk due to paralysis, but is mobile in a wheelchair, subject is considered to be ambulatory for the purpose of assessing their performance status. Absolute neutrophil count (ANC) greater than or equal to 1,000 /mcL (within 28 days prior to study enrollment). Platelets greater than or equal to 50,000 / mcL (within 28 days prior to study enrollment). Hemoglobin greater than or equal to 9 g/dL or greater than or equal to 5.6 mmol/L (within 28 days prior to study enrollment). Calculated creatinine clearance greater than or equal to 30 mL/min creatinine clearance (CrCl) using the Cockcroft-Gault formula (within 28 days prior to study enrollment). Serum total bilirubin less than or equal to 1.5 mg//dl (except for subjects with Gilbert syndrome, who may have total bilirubin less than 3.0 mg/dl) OR direct bilirubin less than or equal to ULN for subjects with total bilirubin levels greater than 1.5 mg/dl (within 28 days prior to study enrollment). Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) less than or equal to 3 X upper limit of normal ULN OR less than or equal to 5 X ULN for subjects with liver metastases (within 28 days prior to study enrollment). Exclusion Criteria: Receipt of > 1 line of systemic therapy directed towards the metastatic disease. NOTE: Systemic therapy as a component of prior definitive therapy directed towards non-metastatic disease will be allowed. For example, patients receiving adjuvant IL-2 after nephrectomy for an initial M0 diagnosis and who subsequently developed metastatic relapse will be allowed on study. In this instance, there will be no mandatory wash-out period required for enrollment. At trial entry the patient must have received their last dose of systemic therapy e.g. last intravenous (IV) administration or oral (PO tablet/pill) administration 4 weeks prior to initiation of the first dose of radiation. Has a diagnosis of active scleroderma, lupus, or other rheumatologic disease which in the opinion of the treating radiation oncologist precludes safe radiation therapy. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial as determined by the treating physician and/or member of the study team. Has a metastatic effusion (e.g. pleural effusion or ascites). Note that patients with an effusion that is too small to sample will be eligible for the trial. Presence of diffuse metastatic processes including leptomeningeal disease, diffuse bone marrow involvement, and peritoneal carcinomatouses, which by the discretion of the treating physician cannot be treated definitively. Is pregnant or expecting to conceive or within the projected duration of the trial at the screening visit. NOTE 1: Female subject of childbearing potential should have a negative urine or serum pregnancy within 28 days prior to study registration up to the first fraction of radiation. NOTE 2: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (SBRT)<br>Patients undergo SBRT over 1 day to 3 weeks based on the judgment of the treating radiation oncologist. | Radiation: Stereotactic Body Radiation Therapy<br>* Undergo SBRT<br>* Other names: Stereotactic Ablative Body Radiation Therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stereotactic body radiation therapy (SBRT) into a treatment plan | Evaluate the feasibility as a component of definitive local treatment for oligometastatic renal cell carcinoma (RCC). | Up to 12 months | 
| Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | The probabilities of participants remaining alive and progression free will be estimated using the Kaplan Meier method with corresponding 95% confidence intervals. | At 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in cellular replication as measured by ki-67 staining | The number of cells with ki-67 staining per 10 high powered fields will be calculated in pre- and post SBRT samples. The percent difference in in ki-67 staining will be calculated by dividing the difference in pre- and post- ki67 staining by the pretreatment ki-67. Will estimate the median relative change with 95% confidence interval. | Baseline up to 12 months | 
| Systemic therapy free survival | The probabilities of patients remaining off systemic therapy at 12 months will be estimated utilizing the Kaplan Meier method with corresponding 95% confidence intervals. | At 12 months | 
| Overall survival | The probabilities of participants remaining alive will be estimated utilizing the Kaplan Meier method with corresponding 95% confidence intervals. | At 12 months | 
| Freedom from new lesion development | A participant will be considered to have a new lesion when standard radiographic imaging identifies a new lesion that is non-contiguous with any other lesions measured at baseline. The probabilities of patients remaining free from new lesions will be estimated utilizing the Kaplan Meier method with corresponding 95% confidence intervals. | At 12 months | 
| Treatment related toxicities associated with SBRT | The frequency of grade 2 and higher toxicities attributable to study treatment will be reported for all patients at all follow up visits. | Up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stereotactic Body Radiation Therapy, Radiation therapy, Malignant neoplasms of urinary tract, Oligometastatic renal cell carcinoma, RCC, SBRT, XRT