Antiandrogen Therapy and Radiation Therapy With or Without Docetaxel in Treating Patients With Prostate Cancer That Has Been Removed by Surgery

PRIMARY OBJECTIVES:

I. To assess the benefit of docetaxel as measured by improvement in freedom from progression
(phase II) and subsequently metastasis free survival (phase III) when given in combination
with radiation and androgen deprivation in treatment of high risk prostate cancer
post-radical prostatectomy.

SECONDARY OBJECTIVES:

I. To assess overall survival. II. To assess local time to progression. III. To assess
undetectable prostate-specific antigen (PSA) with a non-castrate testosterone at 2.5 years
post treatment.

IV. To assess the utility of genomic profiling in making adjuvant therapy decisions
post-prostatectomy.

V. To assess toxicity of docetaxel in the post-operative setting when combined with radiation
and androgen deprivation therapy.

VI. To assess treatment response by genomically defined sub-groups of prostate cancer
patients.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive androgen deprivation therapy comprising leuprolide acetate, goserelin
acetate, bicalutamide, flutamide, or nilutamide for 6 months. Beginning 8 weeks after the
start of androgen deprivation therapy, patients receive external beam radiation therapy
(EBRT) for 7.5 weeks.

ARM II: Patients receive androgen deprivation therapy and EBRT as in Arm I. Within 4-6 weeks
after completion of radiation therapy, patients receive docetaxel intravenously (IV) on day 1
of every 21 days for 6 courses in the absence of disease progression or unexpected toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years,
then every 6 months for 3 years, and then yearly.

Inclusion Criteria:

- Patients post-prostatectomy with baseline Gleason >= 7 (per prostatectomy pathology)
and baseline PSA nadir >= 0.2 ng/ml obtained prior to step 1 registration

- Baseline testosterone level obtained post prostatectomy prior to step 1 registration

- Pathologically (histologically) proven diagnosis of adenocarcinoma of the prostate as
confirmed at time of prostatectomy; prostatectomy must have been performed =< 365 days
(1 year) prior to step 1 registration

- Primary treatment with radical prostatectomy

- Any type of radical prostatectomy is permitted, including retropubic, perineal,
laparoscopic or robotically assisted

- Prior ablative treatment for treatment of benign prostatic hypertrophy or focal
high-intensity focused ultrasound therapy (HIFU) prior to prostatectomy is allowed

- Prior androgen deprivation (luteinizing hormone-releasing hormone [LHRH] agonist
and/or non-steroidal anti-androgen) is allowed if discontinued at least 90 days prior
to study enrollment and given for =< 90 days duration; finasteride or dutasteride must
be stopped before treatment but should not determine eligibility; for patients on
prior LHRH analogs, the discontinuation date should be calculated based the expected
duration of the sustained release injection, not simply the injection date of the drug

- Pathologically proven to be lymph node negative by pelvic lymphadenectomy (pN0) or
lymph node status pathologically unknown (undissected pelvic lymph nodes [pNx])

- Any pT-stage based on American Joint Committee on Cancer 7th edition is acceptable for
study entry based on the following diagnostic workup:

- History/physical examination within 60 days prior to step 1 registration

- No distant metastases, based upon the following minimum diagnostic workup:

- A computed tomography (CT) scan of the abdomen and pelvis (with contrast if renal
function is acceptable; a CT without contrast is permitted if the patient is not
a candidate for contrast) or magnetic resonance imaging (MRI) of the pelvis
within 120 days prior to step 1 registration; lymph nodes will be non-metastatic
unless they measure more than 1.5 cm short axis;

- Bone scan within 120 days prior to step 1 registration (a sodium fluoride [NaF]
positron emission tomography/computed tomography [PET/CT] is an acceptable
substitute); if the bone scan is suspicious, a plain x-ray, CT scan, NaF PET/CT
and/or MRI must be obtained to rule out metastasis

- Eastern Cooperative Oncology Group (ECOG) performance status of =< 1 within 90 days
prior to step 1 registration

- Platelets >= 1 X 10^6 cells/mm^3 (100,000) based upon complete blood count (CBC)

- Hemoglobin >= 10.0 g/dl based upon CBC (Note: The use of transfusion or other
intervention to achieve Hgb >= 10.0 g/dl is not allowed)

- Absolute neutrophil count greater than 1.5 x 10^9/L (1500)

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 1.5 x the upper
limit of normal

- Total bilirubin normal unless history of Gilbert's syndrome

- The patient or a legally authorized representative must provide study-specific
informed consent prior to step 1 registration

- Available surgical formalin-fixed paraffin-embedded (FFPE) specimen for genomic
analysis on DECIPHER Genomic Resource Information Database (GRID) platform

Exclusion Criteria:

- Definitive clinical or radiologic evidence of metastatic disease

- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
for a minimum of 2 years) Ta bladder cancer is not considered invasive

- Prior radiotherapy to the region of the study cancer that would result in overlap of
radiation therapy fields

- Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
different cancer is allowable if completed more than two years prior to step 1
registration; prior androgen deprivation is allowed

- Prior whole gland ablative therapy (i.e. cryoablation or high intensity focused
ultrasound [HIFU]) for prostate cancer is allowed; prior focal HIFU or treatment for
benign prostatic hypertrophy is allowed

- Prostatectomy performed greater than 365 days (1 year) prior to step 1 registration

- Severe and/or active co-morbidity defined as follows:

- History of inflammatory bowel disease

- History of active hepatitis B or C; blood tests are not required to determine if
the patient has had hepatitis B or C, unless the patient reports a history of
hepatitis

- 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 step 1 registration

- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization within 15 days of step 1 registration or precluding
study therapy at the time of step 1 registration

- Uncontrolled severe illness or medical condition (including uncontrolled
diabetes), which in the judgment of the treating physician would make the
administration of chemotherapy inadvisable

- Concurrent or planned treatment with strong inhibitors (e.g. ketoconazole,
clarithromycin, etcetera [etc]) or strong inducers (e.g. carbamazepine,
phenytoin, rifampin, phenobarbital, efavirenz, tipranavir, St. John's wort) of
cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who
are already on these treatments)

- Human immunodeficiency virus (HIV) positive with cluster of differentiation 4 (CD4)
count < 200 cells/microliter; note that patients who are HIV positive are eligible,
provided they are under treatment with highly active antiretroviral therapy (HAART)
and have a CD4 count >= 200 cells/microliter within 30 days prior to step 1
registration; note also that HIV testing is not required for eligibility for this
protocol