Stereotactic Ablative Radiotherapy (SABR) for Low Risk Prostate Cancer With Injectable Rectal Spacer

A phase II study to assess safety and efficacy of the spacer injection process, ability of
the spacer to effectively provide the space necessary to reduce acute events in the rectum,
and also meet the SABR based rectal constraints, and to monitor stability of this process
during SABR. Unlike IMRT, which uses smaller dose/fraction, when using such high
dose/fraction, even a few mm of shift in spacer positioning may impact the dose that the
rectum receives, and therefore, a rigorous study of stability of material during the SABR
treatments will need to be determined. If there is some shift, by doing this study, we may be
able to determine the margin of error that will be necessary in considering rectal organ
dosimetry, based on the possible shift in positiong that may occur with the spacer over time.

As the SABR therapy is strictly local, we will select for patients with prostate cancer
locally confined to the prostate gland. As such, we will select eligibility criteria of low
risk patients to minimize risk of extraprostatic spread, seminal vesicle invasion, and nodal
spread. Hormonal therapy may also be used to shrink prostates that are massively enlarged as
this may also help further reduce length of rectum that will be irradiated. As the primary
toxicity will likely be mucosal damage, we will avoid enrolling patients with pre-existing
mucosal dysfunction (including those with previous radiation, TURP, very large prostate
glands, inflammatory bowel disease) and immunosuppressed individuals based on our phase I
experience[13]. In this way, patients will be uniformly selected in a fashion that would
identify patients likely to receive benefit from the therapy.

Inclusion Criteria:

- All patients must be willing and capable to provide informed consent to participate in
the protocol.

- Eligible patients must have appropriate staging studies identifying them as AJCC stage
T1 (a, b, or c) or T2a or T2b adenocarcinoma of the prostate gland. The patient should
not have direct evidence of regional or distant metastases after appropriate staging
studies. Histologic confirmation of cancer will be required by biopsy performed within
180 days of registration.

- The patient's Zubrod performance status must be 0-2.

- The Gleason score should be less than or equal to 6 or 3+4 if < 50% of a 12 core
biopsy was involved.

- The serum PSA should be less than or equal to 10 ng/ml.

- Study entry PSA must not be obtained during the following time frames: 10 day period
following prostate biopsy; following initiation of ADT; within 30 days after
discontinuation of finasteride; or within 90 days after discontinuation of
dutasteride.

- Age ≥ 18 years.

- Patients may have used prior hormonal therapy, but it should be limited to no more
than 9 months of therapy prior to enrollment.

- The ultrasound, or CT based volume estimation of the patient's prostate gland should
be ≤ 60 grams.

Exclusion Criteria:

- Subjects who have had previous pelvic radiotherapy or have had chemotherapy or surgery
for prostate cancer.

- Subjects who have plans to receive other concomitant or post treatment adjuvant
antineoplastic therapy while on this protocol including surgery, cryotherapy,
conventionally fractionated radiotherapy, hormonal therapy, or chemotherapy given as
part of the treatment of prostate cancer.

- Subjects who have undergone previous transurethral resection of the prostate (TURP) or
cryotherapy to the prostate. Subjects who have significant urinary obstructive
symptoms; AUA score must be ≤15 (alpha blockers allowed).

- Subjects who have a history of significant psychiatric illness.

- Men of reproductive potential who do not agree that they or their partner will use an
effective contraceptive method such as condom/diaphragm and spermacidal foam,
intrauterine device (IUD), or prescription birth control pills.

- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
for a minimum of 3 years (e.g., carcinoma in situ of the breast, oral cavity, or
cervix are all permissible).

- Severe, active co-morbidity, defined as follows:

- Unstable angina and/or congestive heart failure requiring hospitalization within
the last 6 months.

- Transmural myocardial infarction within the last 6 months.

- Acute bacterial or fungal infection requiring intravenous antibiotics at the time
of registration.

- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy within 30 days before
registration.

- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
note, however, that laboratory tests for liver function and coagulation
parameters are not required for entry into this protocol.

- Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition;
note, however, that HIV testing is not required for entry into this protocol. The
need to exclude patients with AIDS from this protocol is necessary because the
treatments involved in this protocol may be significantly immunosuppressive.
Protocol-specific requirements may also exclude immuno-compromised patients.

- Patients with history of inflammatory colitis (including Crohn's Disease and
Ulcerative colitis) are not eligible.

- Subjects with a known allergy to polyethylene glycol hydrogel (spacer material) or
contraindication to spacer products (Duraseal or SpaceOAR).

- Subjects with evidence of extraprostatic extension (T3a) or seminal vesicle
involvement (T3b) on clinical evaluation.