Inclusion Criteria:

- Histologically confirmed prostate cancer

- Stage D0 OR D1 disease (i.e., tumor originally diagnosed as being limited to the
prostate and regional lymph nodes)

- Has a rising PSA value after definitive local therapy (i.e., prostatectomy or
radiotherapy) and no radiographic evidence of disease

- PSA progression after local treatment:

- PSA values for patients after surgery must be ≥ 0.2 ng/mL, determined by two
measurements, ≥ 1 month apart and ≥ 6 months after prostatectomy

- PSA values for patients after radiotherapy must be ≥ 2.0 ng/mL above the nadir
PSA achieved after radiotherapy, determined by two measurements at 1 month apart
and ≥ 6 months after completion of the radiotherapy treatment (patients who
received adjuvant or salvage radiotherapy after prostatectomy must have PSA of ≥
0.2 ng/mL)

- The first two PSA values, along with a third (study baseline) value must all be
rising (i.e., there must be an overall rising trajectory, such that the third
value cannot be lower than the first value)

- No metastatic disease on baseline bone scan and CT scan of the abdomen/pelvis

- ECOG performance status 0-2

- Life expectancy ≥ 6 months

- WBC ≥ 3,000/mm^3

- ANC ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9 g/dL

- Serum creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance ≥ 40
mL/min for patients with creatinine levels above normal

- Bilirubin normal

- AST and/or ALT ≤ 2.5 times ULN

- Serum total testosterone level ≥ 150 ng/dL

- No uncontrolled electrolyte abnormalities including hypocalcemia, hypomagnesemia,
hyponatremia, hypophosphatemia, or hypokalemia, defined as less than the lower limit
of normal despite adequate electrolyte supplementation

- Fertile patients must use two effective forms of contraception (i.e., barrier
contraception and one other method of contraception) for 1 week before, during, and
for ≥ 12 months after completion of study treatment

- Able to swallow tablets

- No malabsorption syndrome or other condition that would interfere with intestinal
absorption

- No uncontrolled concurrent illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- A history of torsades de pointes

- Cardiac arrhythmia other than chronic, stable atrial fibrillation

- Psychiatric illness or social situation that would limit compliance with study
requirements

- Baseline QTc ≤ 450 msec

- No serologic positivity for acute hepatitis A, acute or chronic hepatitis B, or acute
or chronic hepatitis C

- No history of liver disease or other forms of hepatitis or cirrhosis

- No HIV-positive patients on combination antiretroviral therapy

- No serious concurrent systemic disorder that would compromise the safety of the
patient or compromise the patient's ability to complete the study, at the discretion
of the investigator

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to gamma-secretase inhibitor RO4929097 or bicalutamide

- Patients may not donate sperm or blood during or for ≥ 12 months after completion of
study treatment

- No concurrent medications or food that may interfere with the metabolism of RO4929097
including grapefruit and fresh-squeezed grapefruit juice

- Recovered from adverse events to < CTCAE grade 2

- At least 3 months since prior and no concurrent androgen-deprivation therapy (ADT)

- Hormone-ablative treatment is only allowed in the neoadjuvant setting or in the
setting of primary or salvage radiotherapy

- No more than 36 months of neoadjuvant/ adjuvant ADT

- More than 4 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas
or mitomycin C)

- More than 4 weeks since prior and no concurrent estrogens, estrogen-like substances
(i.e., PC-SPES, saw palmetto, or other herbal product that may contain
phytoestrogens), or any other hormonal therapy (including flutamide, nilutamide,
finasteride, ketoconazole, systemic corticosteroids, megestrol acetate, or
cyproterone acetate)

- No other concurrent investigational agents

- No concurrent medications with narrow therapeutic indices that are metabolized by
cytochrome P450 (CYP450), including warfarin sodium (Coumadin®)

- No concurrent medications that are strong inducers/inhibitors or substrates of CYP3A4

- No other investigational or commercial agents or therapies administered with the
intent to treat the patient's malignancy, including chemotherapy, immunotherapy,
hormonal cancer therapy, radiotherapy, or surgery for cancer

- No concurrent hormonal therapy with a leuteinizing hormone-releasing hormone (LHRH)
agonist therapy (e.g., leuprolide or goserelin) or LHRH antagonist (e.g., abarelix)

- No concurrent growth factors (e.g., G-CSF), packed RBC transfusions, or platelet
transfusions

- No concurrent antiarrhythmics or other medications known to prolong QTc