CivaSheet With Radical Prostatectomy & Adjuvant External Beam Radiation

Using preoperative MRI imaging to identify areas suspicious of local advancement in addition
to identifying areas with a higher likelihood of a positive margin during RP due to the
presence of high risk features, Civasheet® and its inherently flexible structure allow the
sheet to be directly implanted on areas suspicious for local advancement and positive
surgical margins for direct application of radiation to these areas. The custom, single
planar layer, integrative gold shielding of Civasheet® also allows radiation to be provided
unidirectionally to allow healthy tissue (i.e., bladder, rectum) to be shielded from
radiation; possibly affording a lower rate of gastrointestinal (GI) and genitourinary (GU)
toxicity and adverse events. During EBRT, radiation especially for high risk PCa is provided
at high rates to the entire prostatic bed with the seminal vesicles, pelvic lymph nodes and a
surrounding margin often targeted to eliminate positive margins and cancer from locally
advanced areas in which the cancer may have spread (i.e., seminal vesicles, bladder neck).
These high rates of radiation often damage surrounding tissue and result in rectal and
bladder complications in addition to urethral strictures among other adverse complications.
Since Civasheet® will provide radiation to the prostatic bed, a lower dose of EBRT will be
used to treat the prostatic bed and potentially lower adverse bladder and rectal effects
compared to RP + RT at 60 Gy. 103 Pd seeds of Civasheet® also illuminate on imaging.
Therefore placing Civasheet® based on pre-operative identification of areas suspicious for
local advancement and areas of likely positive surgical margins during RP will allow for
targeted EBRT to the locally advanced areas. Since EBRT can be targeted using Civasheet®, a
lower and more direct dose of radiation during EBRT may be used to treat local advancement
and positive surgical margins which will potentially reduce toxicity and complications
associated with higher doses of radiation.

The above properties are likely to facilitate improved cancer control with more direct and
local application of radiation to areas of local advancement surrounding the prostate. These
features are also likely to facilitate a reduced complication and toxicity profile since
Civasheet® allows EBRT to be applied more accurately and at a lower dose and also the
unidirectional radiation applied directly by Civasheet® protects surrounding healthy tissue
from receiving radiation.No other studies have attempted to use Civasheet® to improve PCa
control and reduce toxicity and complications associated with radiation for participants with
high-risk prostate cancer. The investigators anticipate that implanting Civasheet® on areas
suspicious for local advancement and positive margins based on pre-operative MRI findings and
identification of high risk features in addition to relying on the illumination provided by
Civasheet® for targeted adjuvant EBRT will provide a safer complication profile and
eventually provide evidence for superior cancer control, lower toxicity and less adverse
events than EBRT+ RP alone in a future randomized controlled trial. The investigators
therefore propose a phase I single-arm open label dose escalation study to evaluate the MTD
and safety of Civasheet® with RP and adjuvant EBRT in a 3+3 dose escalation design among
participants with high risk PCa.With this study, the investigators to better understand the
MTD, safety and toxicity profile of Civasheet® in the setting of RP + adjuvant EBRT in the
treatment of high-risk PCa.

Inclusion Criteria:

- Any subject with National Comprehensive Cancer Network (NCCN) very high or high risk
adenocarcinoma of the prostate defined as ≥T3a, Gleason score ≥ 8, or PSA > 20 who is
eligible for RP (open or robotic) with adjuvant EBRT as an initial treatment option.

- Any subject with NCCN Intermediate Risk adenocarcinoma of the prostate defined as
T2b-T2c, Gleason score 7, or PSA 10-20 who is eligible for RP (open or robotic) with
adjuvant EBRT as an initial treatment option and at least one of the following adverse
features present in pre-operative imaging: seminal vesicle infiltration (SVI),
extracapsular extension (ECE), N1 disease.

- Subject must have had a pre-operative MRI or must obtain a pre-operative MRI to be
eligible for participation in this study.

- Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

- Any subject who has undergone prior radiation to the pelvis.

- Subjects presenting with distant metastases.

- On any investigational drug(s), androgen deprivation therapy or therapeutic device(s)
within 30 days preceding screening.

- Currently taking immunosuppressants, or with poorly controlled diabetes (HbA1c >8).