Stereotactic Body Radiation for Prostate Oligometastases

This research is being done to determine if we can improve the outcome of prostate cancer
patients who have failed primary treatment — surgery or local radiation to the prostate — and
have 3 or fewer bone metastases. Patients with metastatic prostate cancer disease will
usually be placed on hormonal therapy which can work well for a period of time, but hormonal
therapy can have side effects that greatly trouble men. Any effort to delay the start of
hormonal therapy would be an advantage to the patient. Radiation treatment usually takes many
weeks to deliver and is not given in a high enough doses to metastases to prevent them from
coming back locally. Stereotactic body radiation therapy (SBRT) is highly focused radiation,
given in a very dose intensive fashion and delivered in usually less than one week.
Stereotactic body radiation has been shown to be very effective on bone metastases.
Therefore, we are studying the effects of stereotactic body radiation treatment on patients
with five or fewer prostate cancer bone metastases to determine if we can stall the use of
hormonal therapy and/or prevent other bone metastases from developing elsewhere in the body.

Additionally, fundamental analysis of the oligometastatic state with be achieved through
correlation with investigational DCFPyL-PET imaging, which can help us find cancer that has
spread (metastatic disease) from its original site in people who have cancer in their
prostate to other parts of their body.

Specifically, 54 men with biochemically recurrent, oligometastatic prostate adenocarcinoma
will be accrued across 3 centers in the United States. Patients were stratified by primary
intervention (surgery vs radiotherapy), prior hormonal therapy, and PSA doubling time, then
randomized 2:1 to SBRT or observation. The primary clinical endpoint is progression at 6
months from randomization with the hypothesis that SBRT to all metastases will forestall
progression by disrupting the metastatic process. Secondary clinical endpoints include local
control at 6 months post-SBRT, SBRT-associated toxicity and quality of life, and ADT-free
survival (ADT-FS).

Alterations in the biology of the oligometastatic state induced by stereotactic ablative
radiotherapy (SABR) will be investigated using leading-edge correlatives, including: analysis
of circulating tumor cells (CTCs; Epic Sciences, San Diego, CA), deep sequencing of
circulating tumor DNA (ctDNA) using Cancer Personalized Profiling by deep sequencing
(CAPP-Seq) to non-invasively assess tumor burden, and ImmunoSEQ profiling of T-cell
repertoires to elucidate the immunological response to SABR (Adaptive Technologies, Seattle,
WA). Lastly, the use of the Color Genomics platform (Burlingame, CA), a hereditary cancer
assay assessing pathogenic mutations in 30 cancer predisposition genes that account for >90%
of the germline mutations known to occur in men with castrate resistant metastatic prostate
cancer (mCRPC), will help inform and allow for efforts to advance a more personalized
medicine approach to tailor screening and therapies in these men.

Inclusion Criteria:

- Patient must have at least one and up to three asymptomatic metastatic tumor(s) of the
bone or soft tissue develop within the past 6-months that are ≤ 5.0 cm or <250 cm3.

- Patient must have had their primary tumor treated with surgery and/or radiation.

- Histologic confirmation of malignancy (primary or metastatic tumor).

- PSADT <15 months. PSA doubling time (PSADT) will be calculated using as many PSA
values that are available from time of relapse (PSA > 0.2). To calculate PSADT, the
Memorial Sloan Kettering Cancer Center Prostate Cancer

Prediction Tool will be used. It can be found at the following web site:

https://www.mskcc.org/nomograms/prostate/psa-doubling-time.

- Patient may have had prior systemic therapy and/or ADT associated with treatment of
their primary prostate cancer. Patient may have had ADT associated with salvage
radiation therapy (to the primary prostate cancer or pelvis is allowed).

- PSA >1 but <50.

- Testosterone > 125 ng/dL.

- Patient must have a life expectancy ≥ 12 months.

- Patient must have an ECOG performance status ≤ 2.

- Patient must have normal organ and marrow function as defined as:

Leukocytes >2,000/μL Absolute Neutrophil Count >1,000/μL Platelets >50,000/μL

- Patient must have the ability to understand and the willingness to sign a written
informed consent document.

Exclusion Criteria:

- No more than 3 years of ADT is allowed, with the most recent ADT treatment having
occurred greater than 6 months prior to enrollment.

- DCFPyL-PET/MRI or DCFPyL-PET/CT scan within the past 6 months with results that
demonstrate more disease lesions than baseline CT/Bone Scan

- Castration-resistant prostate cancer (CRPC).

- Suspected pulmonary and/or liver metastases (greater >10 mm in largest axis).

- Patient receiving any other investigational agents.

- Patient is participating in a concurrent treatment protocol.

- Total bilirubin > 3 times the upper limit of normal.

- Liver Transaminases > 5-times the upper limit of normal.

- Unable to lie flat during or tolerate PET/MRI, PET/CT or SBRT.

- Liver Transaminases > 5-times the upper limit of normal.

- Prior salvage treatment to the primary prostate cancer or pelvis is allowed.

- Refusal to sign informed consent.