Bicalutamide and RO4929097 in Treating Patients With Previously Treated Prostate Cancer

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