Trial of Salvage Radiation Therapy to Induce Systemic Disease Regression After Progression on Systemic Immunotherapy

Study Groups and Radiation Therapy:

If you are found to be eligible to take part in this study, you will receive radiation
therapy. The radiation oncologist will decide what type of radiation you receive. Depending
on the type of radiation that is chosen for you, you may receive radiation anywhere between 4
days to 3 weeks. The study doctor will discuss what type of radiation you will have and how
often you will receive it. You may be receiving sub-therapeutic doses of radiation.

Within 7 days before you begin radiation therapy, you will have radiation simulation to plan
radiation treatment. During radiation simulation, you will go through the motions of
receiving radiation (though you will not receive radiation) to help you understand the
radiation process. This will also help the doctor know where to "aim" the radiation when you
receive radiation. This may take up to 1 hour.

Study Visits:

At start of your radiation therapy and then every 4-12 weeks while you are on study:

- You will have a physical exam.

- You will have an MRI, CT, or PET/CT scan. You will not have these scans the day after
you receive radiation therapy.

Length of Study:

You may receive radiation for up to 3 weeks. However, you will continue to have study visits
every 4-12 weeks. You will continue having study visits unless the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over after you have completed the follow-up visits
for 1 year.

End-of-Study Visit:

About 30 days after the study stops or you decide to withdraw from the study, you will have a
physical exam and you will be asked about any side effects you may have and if you have had a
change in medication. If you cannot come to MD Anderson for this visit, a member of the study
staff will call you. This call should last about 10 minutes.

Follow-Up:

About every 12 weeks for up to 1 year, you will be asked about any side effects you may have
had and your medical history will be recorded. If you cannot come to MD Anderson for this
visit, a member of the study staff will call you. This call should last about 10 minutes.

After 1 year of follow up, you will continue to have follow-up as part of your standard of
care (collecting information about any side effects you may have and your medical history).
If the follow-up is at another hospital, the information about your medical history, physical
exam, lab tests, PET, MRI, or CT scans will be sent to MD Anderson for review.

Inclusion Criteria:

1. Pathologically confirmed diagnosis of cancer

2. Progressive disease via RECIST 1.1 on prior study or standard of care therapy
utilizing an immunotherapy agent OR a clinical status that requires salvage radiation
treatment (e.g.: palliative RT) at the discretion of treating Physician and/or PI.

3. Be within 6 months (+/-1 week) between last dose of an immunotherapy agent and study
enrollment. *a. Patients may continue with maintenance immunotherapy as part of
standard of care therapy while receiving radiation.

4. Have at least one site of metastatic disease amenable to radiation. All lesions
amenable to radiation may be irradiated at the discretion of treating Radiation
Oncologist, depending on the location, size and number of lesions.

5. Be willing and able to provide written informed consent/assent for the trial.

6. Be >/= 18 years of age on day of signing informed consent.

7. Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG)
performance scale.

8. Female subject of childbearing potential should have a negative urine or serum
pregnancy within 28 days prior to first fraction of radiation. *Note: If the urine
test is positive or cannot be confirmed as negative, a serum pregnancy test will be
required.

9. We will allow prior radiation to other sites, with no washout period, prior to study
entry as long as the high dose regions of the prior and proposed radiation fields do
not overlap or it can overlap, as long as the area being treated is getting low dose
radiation; this can be done alone or in combination with high dose to a previously
un-irradiated area.

Exclusion Criteria:

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

2. Has had prior radiation therapy within the past 3 months where the high dose area of
the prior radiation would overlap with the high dose area of the intended radiation
based on the judgment of the treating radiation oncologist.

3. Has not recovered (i.e., previous treatment. *Note: Subjects with permanent neuropathy) or toxicities corrected through routine medical management (e.g. thyroid
replacement for hypothyroidism) are an exception to this criterion and may qualify for
the study. **Note: If subject received major surgery, they must have recovered
adequately from the toxicity and/or complications from the intervention prior to
starting therapy. ***Note: Subjects with asymptomatic dermatologic abnormalities are an exception to this criterion and may qualify for the
study pending the judgment of the treating radiation oncologist.

4. Has an active infection requiring intravenous systemic therapy or hospital admission.

5. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.

6. Is pregnant or expecting to conceive or within the projected duration of the trial,
starting with the screening visit through 60 days after the last fraction of
radiation.