Clinical Trial Comparing 3-D RT vs. IMRT in Post- Prostatectomy Prostate Cancer Patients

In 2015, the American Cancer Society estimates that almost 220,800 men are expected to be
diagnosed with prostate cancer, and about 27,540 men are expected to die of this disease.
Curative treatment of prostate cancer consists of either surgery (i.e., radical
prostatectomy) or radiation therapy (RT). Approximately one-third of men who undergo a
prostatectomy will require post-operative adjuvant or salvage RT.

During the last 2 decades, the techniques used to deliver RT have evolved from 2-D RT in the
1980's and early 1990's, to 3-D conformal RT (3-D CRT) in the late 1990's, to intensity
modulated radiation therapy (IMRT) within the last decade.

To date, no randomized prospective head to head comparison between 3-D CRT and IMRT to
assess toxicity differences has ever been conducted in the treatment of post-prostatectomy
prostate cancer patients. Retrospective evidence suggests comparable acute and late
genitourinary (GU) and gastrointestinal (GI) toxicity. In addition, no postoperative
randomized trials investigating hormonal therapy (HT) and RT have been published, but three
prior phase III studies of men treated definitively for prostate cancer, one by the
Radiation Therapy Oncology Group (RTOG) (86-10), one by investigators at Harvard, and one by
the Trans-Tasman Radiation Oncology Group, concluded that neoadjuvant and concurrent
short-term hormonal therapy (i.e., 4-6 months) RT reduces cause-specific mortality compared
with RT alone.

The purpose of this study is to estimate, correlate, and compare the incidence of acute
rectal, bladder and other acute toxicities between 3-D CRT and IMRT in prostate cancer
patients treated with post-operative radiation therapy, to quantify, compare, and correlate
the dose volume histogram (DVH) doses (e.g., Vmean, Vmedian, V25, V50, V75) to the
surrounding critical organs (i.e., rectum and bladder) between 3-D CRT and IMRT, and to
measure, compare, and correlate the quality of life scores of participants using the EORTC
Quality of Live Questionnaires (QLQ), called "QLQ-C30" and "EPIC-26". These survey
instruments will measure quality of life differences during the study; the comparison will
be done between 3-D CRT and IMRT treatment arms.

Hormonal therapy will also be required for patients with high risk disease (both the
adjuvant and salvage groups) and as per standard of care for patients with low risk disease,
but is not explored in this study.

There are 2 arms (groups) in this study:

Arm 1: 3-D Conformal Radiation Therapy (plus hormonal therapy)

Arm 2: Intensity Modulated Radiation Therapy (plus hormonal therapy)

INCLUSION Criteria:

Subjects must meet all of the inclusion criteria to participate in this study.

- Histologically documented adenocarcinoma of the prostate.

- Status post radical prostatectomy with sampling of the pelvic lymph nodes with
histologically confirmed adenocarcinoma of the prostate, with the patients falling
into either the "adjuvant low or high risk groups" or the "salvage low or high risk
groups" as indicated below. In those cases where patients undergo a prostatectomy
without any sampling of the pelvic lymph nodes, patients will be also considered
eligible if they are found to have a negative pelvic CT or MRI scan which shows no
evidence of lymphatic nodal metastases after the prostatectomy.

- "Adjuvant High Risk Group" are those patients with an undetectable or
persistent/decreasing PSA levels (before starting therapy) who MUST be able to
start radiation therapy treatments within 6 months of radical prostatectomy with
at least ONE of the 3 disease features:

- Pathologic T2N0 (with no clinical evidence of metastases) and Gleason Score
≥ 8

- Pathologic T3aN0 (with no clinical evidence of metastases) with
Extra-Capsular Extension and Gleason Score ≥ 8

- Pathologic T3bN0 (with no clinical evidence of metastases) with any Gleason
Score

- "Salvage High Risk Group" are those patients who experience a PSA failure
(defined as at least 1 detectable PSA level > 0.2 ng/ml or at least 2
consecutive increases in PSA levels over baseline which are at least 1 month
apart after radical prostatectomy) with at least ONE of the 4 following
features:

- Pathologic T3bN0 disease (with no clinical evidence of metastases),

- Pathologic T2-3aN0 disease (with no clinical evidence of metastases) with
Gleason Score ≥ 8,

- Pathologic T2-3aN0 disease (with no clinical evidence of metastases) with
PSA Doubling Time ≤ 10 months,

- Pathologic T2-3aN0disease (with no clinical evidence of metastases) with
Pre-RT PSA level ≥ 1.0 ng/ml

- "Adjuvant Low Risk Group" are those patients with an undetectable or
persistent/decreasing PSA levels (before starting therapy) who MUST be able to
start radiation therapy treatments within 6 months of radical prostatectomy with
at least ONE of the 2 disease features:

- Pathologic T2N0 (with no clinical evidence of metastases), Gleason Score ≤
7, with positive margins

- Pathologic T3aN0 (with no clinical evidence of metastases) with
Extra-Capsular Extension, Gleason Score ≤ 7, with or without positive
margins

- "Salvage Low Risk Group" are those patients who experience a PSA failure
(defined as at least 1 detectable PSA level > 0.2 ng/ml or at least 2
consecutive increases in PSA levels over baseline which are at least 1 month
apart after radical prostatectomy) with the following feature: - Pathologic
T2-3aN0 disease (with no clinical evidence of metastases) with Gleason Score ≤7,
with or without positive margins

- Neoadjuvant hormonal therapy prior to radical prostatectomy is allowed, and
post-prostatectomy hormonal therapy prior to any protocol therapy is also allowed.

- Prior chemotherapy, and/or radiation therapy is allowed if it has been at least 3
years or longer since those therapies were given from the time of registration, with
the exception of previous pelvic radiation which is NOT allowed under any
circumstances.

- Karnofsky Performance Status ≥ 70. (Appendix A)

- Hematologic parameters must be within the following limits:

- WBC ≥ 3,000/uL

- Platelet Count ≥ 100,000/uL

- Hemoglobin level ≥ 10.0 g/dl

- Patients with a history of an invasive malignancy within the last 3 years are not
eligible for the protocol; patients who are NED from a prior invasive malignancy for
at least 3 years or longer are eligible for the trial. Patients with history of
benign tumors such as a pituitary macroadenomas, meningiomas, or craniopharyngiomas
are eligible as long as the benign tumor is under local control regardless of the
time frame. Patients with concurrent adequately treated basal cell or squamous cell
carcinoma of the skin are also eligible for the protocol.

- Patients must sign an Informed Consent Form.

- Must not have concomitant medical, psychological or social circumstances which would
interfere with compliance with the protocol treatment and follow-up.

- Age ≥ 18 years.

- Men of childbearing potential must be willing to consent to using effective
contraception while on treatment and for a reasonable period thereafter, which should
be for at least 6 months after the completion of protocol therapy.

EXCLUSION CRITERIA

Subjects meeting any of the exclusion criteria at baseline will be excluded from study
participation.

- Patients who have received prior pelvic irradiation are not eligible.

- Any coexisting medical condition precluding full compliance with the study.

- Patients with active infections or known infection with HIV. Testing for HIV status
will not be required.

- Psychological, familiar, sociological or geographical conditions which would not
permit compliance with the study protocol.