Randomized Study of Stereotactic Body Radiation Therapy (SBRT) in Patients With Oligoprogressive Metastatic Cancers of the Breast and Lung

Inclusion Criteria:

- Age 18 or older

- Willing and able to provide informed consent

- Histologically confirmed metastatic TNBC and NSCLC (without EGFR mutation or ALK/ROS1
rearrangement) with metastatic disease detected on imaging. Biopsy of metastasis prior
to enrollment is per treating physician's discretion per standard of care. It is
preferred but not required.

- Patient has received at least first-line prior treatment with systemic therapy (either
cytotoxic or targeted, including maintenance therapies).

- Patients who received prior immunotherapy are allowed.

- Patients who had any prior radiation therapy near or overlapping with the
oligoprogressive sites are allowed to enroll.

- Patients with the following medical conditions precluding them from participating in
other systemic therapy or drug trials are allowed:

- active liver disease, including viral or other hepatitis, or cirrhosis

- any other significant medical condition not under control, including any acute
coronary syndrome within the past 6 months.

- a permanent pacemaker

- a QTc > 480 ms in the baseline EKG

- peripheral neuropathy of grade >/= 2 per NCI CTCAE

- history or known autoimmune disease

- current chronic systemic steroid therapy or any immunosuppressive therapy

- history of primary immunodeficiency or solid organ transplant

- known positive human immunodeficiency virus (HIV), chronic or active hepatitis B or C,
or active hepatitis A

- active infection requiring systemic antibiotic therapy

- Patients can have more than 5 metastases but can only have 1-5 oligo-progressive
lesions.

- Oligoprogression, defined as Response Evaluation Criteria in Solid Tumors (RECIST) or
Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) documented
progression in up to 5 individual lesions

Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria as a guide:

1. At least a 20% increase in the sum of the longest diameter (LD) of the lesion, taking
as reference the smallest sum LD recorded since the last imaging OR

2. The appearance of one or more new lesions OR

3. New/malignant FDG uptake in the absence of other indications of progressive disease or
an anatomically stable lesion OR

4. >/= 5mm increase in the diameter sum of the lesion

OR

Using Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) as a guide:

1. >30% increase in 18F-FDG SUV peak, with >0.8 SUV units increase in tumor SUV from the
baseline scan in pattern typical of tumor and not of infection/treatment effect OR

2. Visible increase in the extent of 18F-FDG tumor uptake OR

3. New 18F-FDG avid lesions typical of cancer (including new bone lesion) and not related
to treatment effect and/or infection

OR

Development of a new soft tissue metastatic lesion at least 5mm in size or any new bone
metastasis

OR

Progressive enlargement of a known metastasis on 2 consecutive imaging studies at least 2
months apart with a minimum 5mm increase in size

- All sites of oligoprogression can be safely treated

- Maximum 5 progressing metastases in any single extra-cranial organ system (i.e. lung,
liver, bone)

- No restriction on the total number of metastases

- For patients with brain metastases and oligoprogression elsewhere where stereotactic
radiation to the brain is warranted, the brain lesions can be treated prior to
randomization. This will not be counted toward the 5 progressive lesions.

- Any symptomatic metastatic sites requiring prompt palliative radiation (e.g. cord
compression) can also be treated with standard fractionation radiation prior to
randomization. This will not be counted toward the 5 progressive lesions.

Exclusion Criteria:

- Pregnancy.

- Leptomeningeal disease.

- Progressive pleural disease or peritoneal implants.

- Serious medical comorbidities precluding radiotherapy, such as ataxia-telangiectasia
or scleroderma.

- Any other condition which in the judgment of the investigator would make the patient
inappropriate for entry into this study.