Study of Effectiveness of IMC-A12 Antibody Combined With Hormone Therapy Prior to Surgery to Treat Prostate Cancer

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.

Inclusion Criteria:

- Men 18 years or older with clinically localized prostate cancer who have chosen
surgery (prostatectomy) and are at high risk of cancer relapse due to clinical stage,
Gleason Score, PSA level, or a combination of the three.

- Good health and laboratory values within reasonable limits

Exclusion Criteria:

- Patients with prostate cancer that has spread outside the prostate.

- Patients who have low testosterone

- Patients who have received hormonal therapies or drugs which affect hormone
metabolism

- Patients with serious medical conditions such as diabetes, other cancers, stroke,
cardiovascular disease.

- Patients who are receiving other investigational therapy or chemotherapy.

- Patients who are unwilling to use contraceptives during and for a short time after
the study

- Inability to give informed consent for any reason