Efficacy and Safety Study of Cetuximab or Cetuximab Plus Docetaxel to Treat Prostate Cancer Before Prostatectomy

With the larger number of men who undergo screening with assays for serum prostate specific
antigen, urologists continue to see considerable numbers of patients with locally advanced
prostate disease. There is a higher risk of treatment failure in any patient with a tumor
that extends through the prostate capsule, more aggressive pathology (Gleason score of 7 or
higher), or patients with a PSA of greater than 10 ng/ml. The rationale for adding molecular
targeted drugs such as Cetuximab (epithelial growth factor inhibitor), with or without
chemotherapy such as Docetaxel, is that such therapy has the potential to demonstrate tumor
shrinkage of the prostate and, in addition, micrometastatic cells. Cetuximab alone or
Cetuximab plus Docetaxel utilizing the preprostatectomy model, with the adjuvant delivery of
Cetuximab for 6 months, will provide data for the following points:

1. demonstration of a PSA response prior to prostatectomy;

2. demonstration whether a change in the natural history, with a delay in the onset of
metastatic disease in patients with advanced local prostate cancer, can be achieved;

3. laboratory and tissue correlation to assess changes in proliferative, apoptosis, and
pathologic parameters; and

4. metabolic imaging utilizing CT-PET with FDG to assess whether this will be a useful
modality in exhibiting a response to therapy, compared with conventional radiographic
imaging.

This will provide the basis for future development of neoadjuvant chemotherapy prior to
prostatectomy.

Inclusion Criteria:

- Histologic proof of prostatic adenocarcinoma without evidence of regional and/or
distant metastasis, clinical stage T1c or T2a with high grade disease (Gleason's
8-10) on initial biopsy, or clinical stage T2b-T2c with Gleason's grade 7 or above
with a PSA ≥ 10ng/ml, or clinical stage T3.

- Recent (< 6 weeks prior to study entry) negative bone scan and MRI of abdomen and
pelvis.

- Appropriate surgical candidate for radical prostatectomy and a performance status of
< 2 (Zubrod scale).

- Patients should have adequate bone marrow function defined as an absolute peripheral
granulocyte count > 1,500 and platelet count of > 100,000, adequate hepatic function
with a bilirubin < 1.5 mg % and SGPT < 2.5x the upper limits of normal, adequate
renal function defined as serum creatinine < 1.5 x ULN.

- Patients must have normal coagulation profile (PT, PTT) and no history of substantial
non-iatrogenic bleeding diatheses. Use of anticoagulants is limited to local use only
(for control of central line patency).

- Patients must have no history of congestive heart failure or previous MI within the
last 12 months.

Exclusion Criteria:

- Previous or current hormonal treatment, chemotherapy, radiation therapy,
immunotherapy or other investigational status drug.

- Unable to tolerate transrectal ultrasound.

- Patients who are not appropriate surgical candidates for radical prostatectomy based
on the evaluation of co-existent medical diseases and competing causes of death.
Patients with uncontrolled cardiac, hepatic, renal or neurologic/psychiatric disorder
are not eligible. Patients with uncontrolled and symptomatic orthostatic hypotension
or uncontrolled hypertension are not eligible.

- Patients who are HIV positive or have chronic hepatitis B or C infections are not
eligible.

- Patients on oral steroid medications are not eligible.

- Patients with significant arteriosclerotic disease, as defined by a previous arterial
bypass claudication limiting activity, or a history of cerebrovascular events within
the last year (including TIA) are not eligible.

- Prior severe infusion reaction to a monoclonal antibody.