A Randomized Phase Ib/II Study of Preoperative GDC-0449 and Androgen Ablation Compared to Androgen Ablation Alone Followed by Radical Prostatectomy for Select Patients With Locally Advanced Adenocarcinoma of the Prostate
I. To assess the difference in less than or equal to 5% tumor involvement between patients
between the two arms.
I. To assess differences in hedgehog signaling, androgen signaling, markers linked to high
grade prostate cancer (PCa) progression, proliferation, apoptosis, and the expression of
androgen producing enzymes in the tumor microenvironment between the two arms.
II. To assess safety of preoperative GDC-0449 in combination with luteinizing
hormone-releasing hormone (LHRH).
III. To assess the difference in proportion of patients with negative disease surgical
margins between the two arms.
IV. To collect and archive tissue from the primary tumor, bone marrow and blood (serum,
plasma), bone marrow aspirate for future study.
V. To assess difference in relapse rate (biochemical, objective) and time to progression.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I (androgen-ablation therapy and Hedgehog antagonist GDC-0449): Patients receive LHRH
analogue comprising leuprolide intramuscularly or goserelin subcutaneously on day 1 and
Hedgehog antagonist GDC-0449 orally once daily on days 1-28. Treatment repeats every 28 days
for up to 16 weeks in the absence of disease progression or unacceptable toxicity.
ARM II (androgen-ablation therapy): Patients receive LHRH analogue comprising leuprolide or
goserelin as in group 1. Treatment repeats every 28 days for up to 16 weeks in the absence
of disease progression or unacceptable toxicity.
After completion of study therapy, patients undergo radical prostatectomy.
Tissue specimens from radical prostatectomy may be analyzed for differences in hedgehog
signaling, androgen signaling, markers linked to prostate cancer progression, proliferation,
apoptosis, and the expression of androgen-producing enzymes in the tumor microenvironment by
reverse transcriptase-PCR and IHC.
After completion of study therapy, patients are followed up every 6 months for up to 8
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Proportion of patients with =< 5% tumor involvement
Up to 8 years
M.D. Anderson Cancer Center
United States: Food and Drug Administration
|M D Anderson Cancer Center||Houston, Texas 77030|