Docetaxel Plus Lycopene in Castration Resistant, Chemotherapy-Naïve Prostate Cancer Patients

PRIMARY OBJECTIVES:

I. To define the prostate-specific antigen (PSA) response rate according to the criteria of
Bubley, et al. (>50% reduction from baseline) in subjects treated with a combination of
docetaxel and lycopene.

SECONDARY OBJECTIVES:

I.To determine the objective response rate (ORR) according to modified RECIST criteria in
patients with measurable disease, following treatment with docetaxel and lycopene.

II. To define the time to PSA progression, according to the response criteria of Scher, et
al., in subjects treated with docetaxel and lycopene.

III. To determine the safety and tolerability of lycopene in combination with docetaxel.

IV. To determine the effects of docetaxel + lycopene therapy on the functioning of the
IGFR-I, selected biomarkers, and docetaxel blood levels in plasma and peripheral blood
mononuclear cells (correlative studies).

OUTLINE:

Patients receive 75 mg/m2 docetaxel intravenously (IV) over 1 hour q 21 days and lycopene 30
mg capsules orally (PO) once daily on days 1-21. Treatment repeats every 21 days for at least
4 courses in the absence of disease progression or unacceptable toxicity.

Inclusion Criteria:

- Patient must have a histological diagnosis of adenocarcinoma of the prostate and 2
rising pre-study PSA values >= 1 ng/ml at least 1 week apart within 28 days prior to
enrollment

- Patients must be unresponsive to androgen-deprivation therapy (ADT), as indicated by a
rising PSA level above the ADT nadir

- Patient must not have received chemotherapy, biologic therapy, or any other
investigational drug for any reason within 28 days prior to start of therapy, and must
have recovered from toxicities of prior therapy to grade 1 or less

- Patients must have been surgically or medically castrated; if the patient is being
treated with medical castration, he must be willing to continue this treatment for the
duration of the study; ADT should not be initiated, terminated, or dose-adjusted
during the study

- Prior external beam radiation therapy (to less than 30% of the bone marrow only) is
allowed; at least 28 days must have elapsed since the completion of radiation therapy
and the patient must have recovered from side effects; prior treatment with
samarium-153 or strontium-86 is allowed if at least eight weeks have elapsed since
dosing, and all toxicities have resolved to grade 1; soft tissue disease which has
been radiated in the prior 2 months is not assessable as measurable disease

- Patients may have received prior surgery; however, at least 21 days must have elapsed
since completion of surgery and the patient must have recovered from all side effects

- Normal serum bilirubin and serum glutamic oxaloacetic transaminase (SGOT) or serum
glutamic pyruvate transaminase (SGPT) =< 1.5 x the institutional upper limit of normal
obtained within 14 days prior to start of therapy; liver function tests should be
evaluated prior to each treatment

- Serum creatinine =< 1.5 x the institutional upper limit of normal obtained within 14
days prior to start of therapy

- Men of child bearing potential must be willing to consent to using effective
contraception while on treatment and for at least 3 months thereafter

- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Absolute neutrophil count >= 1,500/microliter (mcL)

- Hemoglobin of >= 8.0gm/dL

- White blood cell count > 2,500/mcL

- Platelets >= 100,000/mcL

- Patients with lower values may participate if, in the opinion of the investigator, the
cytopenias are the result of bone marrow involvement with active prostate cancer

- Patients must be able to take oral medications

- All patients must be informed and must sign and give written informed consent in
accordance with institutional and federal guidelines; patients who are unable to
comply with study and/or follow-up procedures are ineligible

Exclusion Criteria:

- Uncontrolled brain or spinal cord metastases

- History of congestive heart failure or myocardial infarction within the previous six
months

- History of allergy or hypersensitivity to any component of the study drugs

- Evidence or history of a bleeding diathesis or coagulopathy, including therapy-induced
coagulopathy

- Presence of chronic diarrhea (> grade 1 by Common Toxicity Criteria (CTC)), short
bowel syndrome, pancreatic insufficiency, or malabsorption

- Presence of any severe or uncontrolled concurrent medical condition which, in the
opinion of the investigator, would increase the risk of serious toxicity from the
study drugs

- Concurrent use of any vitamin, herb, or mineral supplements for at least 14 days prior
to start of therapy