Stereotactic Ablative Radiotherapy (SABR) of Pelvis and Prostate Targets For High Risk Prostate Cancer

Patients will be accrued in alternating dose levels. The two distinct areas of dose
escalations (pelvic lymph node and prostate lesion) will take place one at a time. Minimum
waiting periods will be assigned between each dose cohort to observe toxicity. The phase I
portion of the study will be completed when dose limiting toxicity is reached or when a
sufficiently high dose level (i.e.,5.5 Gy per fraction to a total 27.5 Gy for pelvic lymph
node region and 11Gy per fraction to a total of 55Gy to the prostate lesion), is attained to
consider the therapy likely to be efficacious. All patients will be treated with a total of
24 months of androgen suppression therapy (ADT). Radiation therapy will start 8-12 weeks
after initiation of ADT.

No. Patients for each cohort: 7-15 Cohort 1: 9.5 Gy per fraction to prostate/SV, 10 Gy per
fraction to prostate lesion, 4.5Gy per fraction to pelvic lymph node region for 5 fractions
for a total of 47.5 / 50 / 22.5 Gy to Prostate+SV /Prostate lesions/Nodes Cohort 2: 9.5 Gy
per fraction to prostate/SV, 10 Gy per fraction to prostate lesion, 5Gy per fraction to
pelvic lymph node region for 5 fractions for a total of 47.5 / 50 / 25 Gy to Prostate+SV
/Prostate lesions/Nodes Cohort 3: 9.5 Gy per fraction to prostate/SV, 10.5 Gy per fraction to
prostate lesion, 5Gy per fraction to pelvic lymph node region for 5 fractions for a total of
47.5 / 52.5 / 25 Gy to Prostate+SV /Prostate lesions/Nodes Cohort 4: 9.5 Gy per fraction to
prostate/SV, 10.5 Gy per fraction to prostate lesion, 5.5 Gy per fraction to pelvic lymph
node region for 5 fractions for a total of 47.5 / 52.5 / 27.5 Gy to Prostate+SV /Prostate
lesions/Nodes Cohort 5: 9.5 Gy per fraction to prostate/SV, 11 Gy per fraction to prostate
lesion, 5.5 Gy per fraction to pelvic lymph node region for 5 fractions for a total of 47.5 /
55 / 27.5 Gy to Prostate+SV /Prostate lesions/Nodes

Inclusion Criteria:

- Signed study specific informed consent form.

- PSA ≥20

- OR Gleason score ≥ 8

- OR Appropriate staging studies identifying as AJCC stage cT3+

- (MR stage T3a without other high risk factors permitted at investigator
discretion).

- No direct evidence of regional or distant metastases after appropriate staging studies
as indicated clinically.

- Clinically negative lymph nodes as established by imaging (abdominal and pelvic CT or
abdominal and pelvic MRI), nodal sampling, or dissection within 90 days prior to
registration.

- Patients with lymph nodes equivocal or questionable by imaging are eligible if the
nodes are < 2.0 cm in the short axis.

- No distant metastases (M0) on bone scan within 90 days prior to registration.

- Histologic confirmation of cancer by biopsy

- Adenocarcinoma of the prostate

- Age ≥18

- Zubrod Performance Status 0-2

- AUA score must be ≤20 (alpha blockers allowed)

- CT or Ultrasound-based volume estimation of prostate gland ≤80 grams (repeat
ultrasound measurement after hormone downsizing allowed)

- Agreement to use effective contraceptive methods such as condom/diaphragm and
spermicidal foam, intrauterine device, or prescription birth control pills.

- Equivocal bone scan findings are allowed if plain films are negative for metastasis.

- Deemed eligible for Complete Androgen Blockade (CAB) hormone therapy by treating
physician, including baseline liver function evaluation. For patients not eligible for
anti-testosterone therapy, hormone therapy with LHRH agonist alone will be permitted
on case by case basis by study P.I.

- Use of previous hormonal therapy for up to 9 months is allowed for the treatment of
prostate cancer as well as for prostate volume reduction.

- MRI Pelvis/Prostate feasible for staging and planning

- Clinically eligible for rectal spacer insertion (e.g. Duraseal, SpaceOAR, or
equivalent product) per physician evaluation

Exclusion Criteria:

- Positive lymph nodes or metastatic disease from prostate cancer by imaging studies (CT
or MRI), unless biopsy proven to be negative.

- Evidence of metastatic disease by imaging study

- Prior invasive malignancy unless disease free for a minimum of 3 years (oral cavity,
or non-melanomatous skin cancer are all permissible)

- Previous pelvic radiotherapy

- Previous surgery or chemotherapy for prostate cancer

- Previous transuretheral resection of the prostate (TURP) or cryotherapy to the
prostate

- Previous androgen depravation therapy given for more than 9 months prior to therapy

- Concomitant antineoplastic therapy (including surgery, cryotherapy, conventionally
fractionated radiotherapy, and chemotherapy) while on this protocol.

- History of Crohn's Disease or Ulcerative Colitis.

- Not actively on immunosuppressive medications.

- Previous significant obstructive symptoms; AUA score must be ≤20 (alpha blockers
allowed)

- Significant psychiatric illness

- Men of reproductive potential may not participate unless they agree to use an
effective contraceptive method.

- Ultrasound or CT estimate of prostate volume > 80 grams (after hormone downsizing
allowed).

- Severe, active co-morbidity

- No nodal disease

- No known allergies to spacer material: Polyethylene glycol (PEG) hydrogel