A Phase II Trial of Combination Therapy With Celecoxib and Taxotere for the Treatment of Stage D3 Prostate Cancer

The standard hormone therapy for patients with metastases is androgen deprivation. This
treatment leads to response in 75-80% of the patients, with median duration of response of
only 14-18 months. Once the patient becomes hormone resistant, there is no effective therapy
to prolong life. For patients with HRPC, the median life expectancy is 17 months.2 Thus
palliative care remains the standard therapy for HRPC. The most widely used chemotherapy
regimens are combinations of mitoxantrone with prednisone and taxanes with estramustine
phosphate.3,4,5 Taxotere has also demonstrated activity in prostate cancer cell lines.6
Several clinical studies have demonstrated its activity in patients with metastatic prostate
cancer as a single agent or in combination.4, 5 Taxotere may exert its effects in part
through anti-angiogenic effects.7 Recent work in animal models has provided additional
evidence for the beneficial role of angiostatic agents in the treatment of malignant
diseases. This is the first study of the two drugs used together in prostate cancer.

Inclusion Criteria:

- Patient must have histologically proven adenocarcinoma of the prostate gland.

- Patient must have evidence of progressive metastatic disease (e.g., bone, pelvic
mass, lymph node, liver or lung metastases) within 6 weeks prior to participation in
the study.

- Patients who have evaluable but not measurable disease must not have an elevated PSA
level as the only evidence of disease. While castrated, the patients should have
rising PSA on two consecutive measurements at least 1 week apart. The confirmatory
PSA must be obtained within 1 week prior to study registration and should be
>10ng/ml.

- Patients with bone metastases only (i.e., lacking soft-tissue disease) must have a
PSA level of > 10 ng/ml. Patients with soft tissue metastases and /or visceral
disease must have either measurable disease or a PSA level of > 10 ng/ml.

- Radiological evidence of hydronephrosis will not by itself constitute evidence of
metastatic disease.

- Patients must have had prior treatment with bilateral orchiectomy or other primary
hormonal therapy (e.g., estrogen therapy, LHRH analog + flutamide, etc.) with
evidence of treatment failure.

NOTE: patients who have not undergone bilateral orchiectomy must continue LHRH agonist
therapy (e.g., depot leuprolide or goserelin) while receiving this protocol therapy. For
these patients the testosterone level should be preferably checked before enrollment and
should be < 50 ng/dl.

- For patients previously treated with flutamide (Eulexin), nilutamide (Nilandron), or
bicalutamide (Casodex): Patients must have discontinued flutamide or nilutamide < 4
weeks and for bicalutamide 6 weeks prior to registration.

- Patients must not have received prior treatment with chemotherapy within the last 5
years.

- Patients must not have had prior radiotherapy < 4 weeks prior to this protocol
treatment.

- Patients must not have previously received Strontium 89, Samarium 153, or other
radioisotope therapies.

- Patients must have recovered from all toxicities due to prior treatment for prostate
cancer prior to receiving this protocol treatment.

- Patients must have adequate bone marrow function: (WBC > 4000/ mm3, granulocytes >
1500/ mm3, platelet count > 100,000/mm3, and Hemoglobin > 8.0 g/dl < 4 weeks prior to
participate in this study.

- Patients must have the following chemistry values < 4 weeks prior to participate in
this study:

- Total bilirubin must be within normal limits.

- Creatinine < 2.0 mg/d. or creatinine clearance > 50 ml/min

- Transaminases (SGOT and/or SGPT) may be up to 2.5 x institutional upper limit of
normal (ULN) if alkaline phosphastase is < ULN, or alkaline phosphastase may be up to
4 x ULN if transaminases are < ULN.

- Peripheral neuropathy must be < grade 1

- Patients must have no active angina pectoris, or known heart disease of New York
Heart Association Class III-IV. Patients must not have a history of myocardial
infarction < 6 months prior to the study participation.

- Patients with a history of prior malignancy are eligible provided they were treated
with curative intent and have been free of disease for the time period considered
appropriate for the specific cancer.

- No serious concurrent medical illness or active infection should be present which
would jeopardize the ability of the patient to receive the chemotherapy outlined in
this protocol with reasonable safety.

- Sexually active patients must use an accepted and effective method of contraception
while receiving protocol treatment.

- Patients must have a Karnofsky Performance Scale (KPS) score over 50. (equaling ECOG
Performance Scale of 0, 1, or 2).

- Age > 18 years

Exclusion Criteria:

- Patients with a history of severe hypersensitivity to Taxotere or other drugs
formulated with polysorbate 80 must be excluded