A Randomized Phase II Study of Peripheral Androgen Blockade With Bicalutamide Followed by Placebo or Treatment With the Gamma Secretase Inhibitor RO4929097 in Men With Rising PSA After Definitive Local Therapy for Adenocarcinoma of the Prostate
I. To determine the difference in the time to PSA progression in patients with
adenocarcinoma of the prostate who have rising PSA after definitive local therapy treated
with bicalutamide with vs without gamma-secretase/Notch signalling pathway inhibitor
I. To determine the proportion of patients from each arm who achieve complete response (by
PSA) during the combination phase.
II. To determine the proportion of patients from each arm with PSA progression during the
III. To determine the time to PSA nadir during the combination phase for patients in each
IV. To determine the time to PSA progression during the combination phase for patients in
V. To determine the time to PSA progression during the observation phase. VI. To determine
the proportion of patients with PSA progression during the observation phase.
VII. To assess the safety and tolerability of gamma-secretase inhibitor RO4929097 in
combination with bicalutamide.
VIII. To evaluate expression for targets of gamma secretase inhibitor in a prostate tissue
IX. To collect serum for future evaluation of soluble markers of gamma-secretase inhibition
OUTLINE: This is a multicenter study.
INDUCTION PHASE: All patients receive induction therapy comprising oral bicalutamide once
daily for at least 16 weeks. Patients whose PSA declines at least 50% continue to the
RANDOMIZATION PHASE: Patients are stratified according to prior therapy (radiotherapy vs
surgery) and randomized to 1 of 2 treatment arms.
ARM I: Patients receive oral placebo once daily on days 1-3, 8-10, and 15-17. Treatment
repeats every 21 days for 18 courses in the absence of PSA progression.
ARM II: Patients receive oral gamma-secretase/Notch signalling pathway inhibitor RO4929097
(RO4929097) once daily on days 1-3, 8-10, and 15-17. Treatment repeats every 21 days for 18
courses in the absence of PSA progression.
Patients with no disease progression continue to the combination phase. Patients with
disease progression undergo imaging studies to verify the absence of metastatic disease
before continuing to the combination phase.
COMBINATION PHASE: All patients then receive oral bicalutamide once daily on days 1-21 and
oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days for 12
months in the absence of disease progression or unacceptable toxicity.
Blood and tumor tissue samples may be collected periodically for correlative studies. After
completion of study treatment, patients are followed up every 6 weeks for 12 months.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Time to PSA progression
Time to PSA progression will be compared in the two groups using a log-rank test.
Up to 12 months
UMDNJ - Robert Wood Johnson University Hospital
United States: Food and Drug Administration
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