Phase II Study of Neoadjuvant IMC-A12 Combined With Androgen Deprivation Prior to Prostatectomy
Androgen deprivation has long been the principal means of controlling advanced prostate
cancer, but it does not cure the disease and all patients ultimately progress if tumor is
not eliminated with definitive local therapy. Neoadjuvant androgen deprivation prior to
radical prostatectomy can downstage localized disease and reduce the likelihood of residual
disease at the margins, but does not improve failure free survival. It has been
demonstrated that despite androgen deprivation with luteinizing hormone releasing hormone
(LHRH) agonists or orchiectomy, prostate tissue and prostate cancer maintain levels of
androgens which are more than adequate to continue to stimulate the androgen receptor and
downstream signaling. These levels of androgen may continue to allow both survival of tumor
cells and induction of resistance by overexpression of receptor.
The anti-insulin-like growth factor type I receptor (IGF-IR) antibody IMC-A12 blocks
translocation of the androgen receptor to the nucleus, dramatically augmenting efficacy of
androgen deprivation in human prostate xenograft models. The combination of androgen
deprivation with IMC-A12 is anticipated to more effectively treat cancer within the
prostate, optimizing local control, while potentially eliminating micrometastatic disease.
We propose to test this hypothesis in this phase II study, administering neoadjuvant
androgen deprivation therapy IMC-A12 prior to radical prostatectomy for patients with
clinically localized, high risk prostate cancer for 3 months.
Patients with clinically localized, and surgically resectable (cT1-T3) prostate cancer, at
high risk for relapse who are candidates for radical prostatectomy will be treated with LHRH
agonist and androgen receptor antagonist combined with IMC-A12, 10 mg/kg given intravenously
every 14 days for 12 weeks. Patients will undergo biopsy of the prostate prior to treatment
and radical prostatectomy 12 weeks after initiation of treatment.
The primary endpoint of the study is to evaluate the ability of LHRH agonist with IMC-A12 to
induce a complete pathologic remission
Samples from the current study will be compared to control, untreated prostatectomy
specimens from the Northwest Prostate SPORE Tissue Core and a concurrent set of specimens
from patients treated with 12 weeks of combined androgen deprivation.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The primary endpoint of the study is to determine the effects of combining androgen deprivation with IMC-A12 on pathologic tumor stage (pathologic complete response).
At the time of prostatectomy after 3 months of treatment
Bruce Montgomery, M.D.
University of Washington and Seattle Cancer Care Alliance
United States: Food and Drug Administration
|University of Washington Medical Center||Seattle, Washington 98195-6043|
|Virginia Mason Medical Center||Seattle, Washington 98111|
|Seattle Cancer Care Alliance||Seattle, Washington 98109|