Bicalutamide and RO4929097 in Treating Patients With Previously Treated Prostate Cancer
Condition: Adenocarcinoma of the Prostate; Recurrent Prostate Cancer; Stage IV Prostate Cancer
MeSH terms: Prostatic Neoplasms; Adenocarcinoma
Intervention: placebo; gamma-secretase/Notch signalling pathway inhibitor RO4929097; bicalutamide
Intervention description: Given orally; Given orally; Given orally
Intervention MeSH terms: Bicalutamide; 2,2-dimethyl-N-(6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-N'-(2,2,3,3,3-pentafluoropropyl)malonamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 10.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This partially randomized phase II trial is studying how well giving bicalutamide together
      with RO4929097 works in treating patients with previously treated prostate cancer. Androgens
      can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide, may
      lessen the amount of androgens made by the body. RO4929097 may stop the growth of tumor cells
      by blocking some of the enzymes needed for cell growth. Giving bicalutamide together with
      RO4929097 may be an effective treatment for prostate cancer
    

Eligibility criteria:

        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