Study of Stereotactic Body Radiation Therapy for Oligometastatic Renal Cell Carcinoma

Study Therapy:

If you are found to be eligible to take part in this study, you will receive radiation
therapy, surgery, and/or other local therapies.

The study doctor will discuss with you the dose and schedule of radiation that you will
receive, based on the disease site.

You may ask the treating doctor for more information about standard-of-care surgery and the
other local therapies, how they are given, and their risks. You will be asked to sign
separate consent forms.

Length of Study Participation:

Your radiation doctor will decide how long you continue receiving radiation treatment. It can
take 1 day to 3 weeks.

Local therapy may take from a few weeks to months to complete. This will vary depending on
the number of disease sites that need to be treated. With radiation, it can take from 1 day
to 3 weeks. You will then be monitored and no local therapy will be given.

If the disease spreads to a new lesion that can be treated with local therapy, you will be
allowed to receive local therapy on study without starting systemic therapy, if the treating
doctor (medical oncologist) thinks it is appropriate. Local therapy again would usually take
1 day to 3 weeks.

The doctor will discuss this schedule with you.

You will be taken off study during or after the treatment period if the disease gets worse
and you start systemic therapy (therapy within the bloodstream) directed towards disease that
has spread, if you develop an illness that prevents your participation, or if you are unable
to follow study directions. If this happens, you will enter the follow-up period.

Your participation on the study will be over after the follow-up.

Study Visits:

On the day you complete radiation or 1 day later, blood (about 4 teaspoons) will be drawn for
routine tests.

At 6 weeks and then every 12 weeks after completing local therapy:

- You will have a physical exam.

- Blood (about 4 teaspoons) will be drawn for routine tests.

- You will have imaging to check the status of the disease.

- At Week 12 only, you will have a tumor biopsy of the site that was treated with
radiation to check the status of the disease and to find out the amount of immune cells
that have entered the tumor.

If the disease gets worse, blood (about 4 teaspoons) will be drawn for routine tests within 4
weeks of the disease getting worse.

Long-Term Follow-Up:

About every 18 weeks for 1 year, a member of the study team may review your medical charts or
call you or a family member to ask how you are doing. The calls should last about 5-10
minutes. If you are already scheduled to be in clinic around these time points, you will also
have a physical exam and imaging performed.

Inclusion Criteria:

1. Oligometastatic RCC patients (less than or equal to 5 sites of metastases at the time
of study entry).

2. Pathologically confirmed diagnosis of RCC of any histology.

3. At least one site which in the opinion of the treating radiation oncologist is
treatable with SBRT and can be biopsied.

4. 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. 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).

5. Be greater than or equal to 18 years of age on the day of signing informed consent.

6. 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.

7. Demonstrate adequate organ function as defined below, all screening labs should be
performed within 28 days prior to study enrollment.

8. Hematological: Absolute neutrophil count (ANC) greater than or equal to 1,000 /mcL,
Platelets greater than or equal to 50,000 / mcL, Hemoglobin greater than or equal to 9
g/dL or greater than or equal to 5.6 mmol/L, Renal: Calculated creatinine clearance
greater than or equal to 30 mL/min creatinine clearance (CrCl) using the
Cockcroft-Gault Formula. Hepatic: 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, 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

Exclusion Criteria:

1. Receipt 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.

2. Has a diagnosis of active scleroderma, lupus, or other rheumatologic disease which in
the opinion of the treating radiation oncologist precludes safe radiation therapy.

3. 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.

4. 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.

5. Presence of diffuse metastatic processes including leptomeningeal disease, diffuse
bone marrow involvement, and peritoneal carcinomatoses, which by the discretion of the
treating physician cannot be treated definitively.

6. 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.